Journal of Cancer Research and Treatment

Current Issue» Volume 2, Number 3 (2014)

Article

Abrogation by Curcumin on Testicular Toxicity Induced by Cisplatin in Rats

1Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt


Journal of Cancer Research and Treatment. 2014, 2(3), 64-68
DOI: 10.12691/jcrt-2-3-4
Copyright © 2014 Science and Education Publishing

Cite this paper:
Ehab Tousson, Ezar Hafez, Ahmed Masoud, Aya A. Hassan. Abrogation by Curcumin on Testicular Toxicity Induced by Cisplatin in Rats. Journal of Cancer Research and Treatment. 2014; 2(3):64-68. doi: 10.12691/jcrt-2-3-4.

Correspondence to: Ehab  Tousson, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt. Email: toussonehab@yahoo.com

Abstract

Cisplatin is one of the most effective and widely-used antineoplastic agents for the treatment of testicular germ cell tumors. The present study was conducted to examine the possible modifying effects of curcumin against testicular toxicity induced by cisplatin in male rats. 60 male albino rats were equally divided into six groups; the first and second groups were the control and curcumin treated group respectively while the 3rd group was cisplatin treated group; the 4th and 5th groups were co- and post treated cisplatin rat with curcumin respectively and the 6th group was self treated cisplatin rat group. Many side effects were observed in animals injected with cisplatin such as loosing of body weight, loss of activity, weakness, yellowish body hair. A significant decrease in the body and testicular weights,, sperm counts, sperm motility, plasma testosterone, luteinizing hormone reduced glutathione, total antioxidant capacity, and total protein levels in cisplatin and cisplatin self treated groups when compared with the control group. On the other hand; a significant increase in the MDA and NO in cisplatin and cisplatin self treated groups when compared with the control group. sperm count and sperm motility, GSH and TAC exhibited significant increased in cisplatin treated with curcumin when compared with cisplatin groups, moreover, sperm abnormality, MDA, NO and total protein exhibited significant decrease in cisplatin treated groups with curcumin when compared with cisplatin groups. A significant decrease in sperm abnormality, MDA, NO and total protein and a significant increase in GSH and TAC in Co-treated group when compared with post treated cisplatin with curcumin. Our recommendation, administration of curcumin caused ameliorative effect against cisplatin-induced testicular toxicity.

Keywords

References

[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[
[1]  Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. Review Oncol Rep 2003; 10 (6): 1663-1682.
 
[2]  Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7 (8): 573-584.
 
[3]  Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31 (15): 1869-1883.
 
[4]  Cohen SM, Lippard SJ. Cisplatin: from DNA damage to cancer chemotherapy. Prog Nucleic Acid Res 2001; 67: 93-130.
 
[5]  Victoria Cepeda, Miguel A. Fuertes, Josefina Castilla, Carlos Alonso, Celia Quevedo and Jose M. Pérez Biochemical Mechanisms of Cisplatin Cytotoxicity. Anticancer Agents Med Chem 2007; 7 (1): 3-18.
 
Show More References
[6]  Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sc 2000; 57 (8-9): 1229-1235.
 
[7]  Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 2009; 30 (2): 85-94.
 
[8]  Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M, Somay A. Potential chemoprotective effect of melatonin in cyclophosphamide and cisplatin-induced testicular damage inrats. Fertil Steril 2009; 92 (3): 1124-1132.
 
[9]  Noorafshan A, Karbalay-Doust S, Valizadeh A, Aliabadi E. Ameliorative effects of curcumin on the structural parameters of seminiferous tubules and Leydig cells in metronidazole-treated mice: a stereological approach. Exp Toxicol Pathol 2011; 63 (7): 627-633.
 
[10]  Khorsandi L, Mirhoseini M, Mohamadpour M, Orazizadeh M, Khaghani S. effect of curcumin on dexamethasone-induced testicular toxicity in mice. Pharm Biol 2013; 51 (2): 206-212.
 
[11]  Payton F, Sandusky P, Alworth WL, RMN Study of the SolutionStructure of Curcumin. J Nat Prod 2007; 70 (2): 144-146.
 
[12]  Goel A, Jhurani S, Aggarwal BB. Multi-targeted therapy by curcumin: how spicy is it? J Nat Prod 2008; 70 (2): 143-146.
 
[13]  Choudhary D, Chandra D, Kale RK. Modulation of radioresponse of glyoxalase system by curcumin. J Ethnopharmacol 1999; 64 (1): 1-7.
 
[14]  Sanchez-Gonzalez PD, Lopez-Hernandez FJ, Perez-Barriocanal F, Morales AI, Lopez-Novoa JM. Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity; Nephrol Dial Transplant 2011; 26 (11): 3484-3495.
 
[15]  Seed J., Chapin R.E., Clegg E.D., Dostal L.A., Foote R.H., Hurtt M.E., Klinefelter G.R., Makris S.L., Perreaultys S.D., Schrader S., Seyler D., Sparando R, Treine KA, Veeramacheneni DNR, Wise LD. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. Reprod Toxicol 1996; 10 (3): 237-244
 
[16]  Cheng D, Zheng X M, Li S W, Yang Z W and Hu L Q. Effects of epidermal growth factor on sperm content and motility of rats with surgically induced varicoceles. Asian J Androl 2006; 8 (6): 713-717.
 
[17]  Abraham GE, Manlimos FS, Garza R. Radioimmunoassay of steroids. Chap. 20 in Handbook of Radioimmunoassay, GE Abraham, Ed., Marcel Dekker, Inc., New York, NY, 1977, pp 591-656
 
[18]  Taylor, A.E., McCourt, B., Martin, K.A., Anderson EJ, Adams JM, Schoenfeld D, Hall JE. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997;82, 2248-2256.
 
[19]  Koracevic, JD, Koracevic G, Djordjevic V, Andrejevic S. and Cosic V. Method for the measurement of antioxidant activity in human fluids. Clin Pathol 2001; 54: 356-361.
 
[20]  Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.
 
[21]  Satoh, K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clinica Chimica Acta 1978; 90: 37-43.
 
[22]  Beutler E, Duron O, and Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882-888.
 
[23]  Montgomery HAC, Dymock JF. The determination of nitrate in water. Analyst 1961; 86: 414-416.
 
[24]  Rebillard A, Lagadic-Gossmann D, Dimanche-Boitrel MT Cisplatin cytotoxicity: DNA and plasma membrane targets. Curr Med Chem 2008; 15 (26): 2656-2663.
 
[25]  Park GY, Wilson JJ, Song Y, Lippard SJ. Phenanthriplatin, a monofunctional DNA-binding platinum anticancer drug candidate with unusual potency and cellular activity profile. Proc Natl Acad Sci U S A 2012; 109 (30): 11987-11992.
 
[26]  Sadowitz PD, Hubbard BA, Dabrowiak JC, Goodisman J, Tacka KA, Aktas MK, Cunningham MJ, Dubowy RL, and Souid A-K. Kinetics of cisplatin binding to cellular DNA and modulations by thiol-blocking agents and thiol drugs. Drug Metab Dispos 2002; 30: 183-190
 
[27]  Shirwaikar A, Issac D, Malini S Effect of Aerva lanata on cisplatin and gentamicin models of acute renal failure. J Ethnopharmacol 2004; 90 (1): 81-86.
 
[28]  Helmy MW, Helmy MM, Abd Allah DM, Abo Zaid AM, Mohy El-Din MM. Role of nitrergic and endothelin pathways modulations in cisplatin-induced nephrotoxicity in male rats. J Physiol Pharmacol 2014; 65 (3): 393-399.
 
[29]  Turk G, Atessahin A, Sçnmez M, Ceribasi AO, YuceA. Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rattestis by ellagic acid. Fertil Steril 2008; 89 (5): 1474-1481
 
[30]  Beytur A, Ciftci O, Oguz F, Oguzturk H, Yilmaz F. Montelukast attenuates side effects of cisplatin including testiculars morphologica and hormonal damage in male rats. Cancer Chemother Pharmacol 2012; 69 (1): 207-213.
 
[31]  Pogach LM, Lee Y, Giglio W, Naumoff M, Huang HF. Zinc acetate pretreatment ameliorates cisplatin-induced Sertoli cell dysfunction in Sprague-Dawley rats.Cancer Chemother Pharmacol 1989; 24 (3): 177-180.
 
[32]  Ateşşahin A, Sahna E, Türk G, Ceribaşi AO, Yilmaz S, Yüce A, Bulmuş O. Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res 2006; 41 (1): 21-27.
 
[33]  Silici S, Ekmekcioglu O, Eraslan G, Demirtas A. Antioxidative effect of royal jelly in cisplatin-induced testes damage. Urology 2009; 74 (3): 545-551.
 
[34]  Rezvanfar MA, Rezvanfar MA, Shahverdi AR, Ahmadi A, Baeeri M, Mohammadirad A, Abdollahi M. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles. Toxicol Appl Pharmacol 2013: 266 (3): 356-365.
 
[35]  Waseem M, Parvez S. Mitochondrial dysfunction mediated cisplatin induced toxicity: modulatory role of curcumin. Food Chem Toxicol 2013; 53: 334-342.
 
[36]  Keshtmand Z, Oryan S, Ghanbari A, Khazaei M. Protective Effect of Tribulus terrestris Hydroalcoholic Extract against Cisplatin-Induced Cytotoxicity on Sperm Parameters in Male Mice. Int J Morphol 2014; 32 (2): 551-557
 
[37]  Richie JP, Jr, Skowronski L, Abraham P, Leutzinger Y. Blood glutathione concentrations in a large-scale human study. Clin Chem 1996; 42 (1): 64-70.
 
[38]  Kandemir, FM, Benzer F, Yildirim NC, Ozdemir N. Compensatory effects of curcumin on cisplatin-induced toxicity in rabbit testis. J Med Plants Res 2011; 5 (3) 456-461.
 
[39]  Serafini M, Del Rio D. Understanding the association between dietary antioxidants, redox status and disease: is the total antioxidant capacity the right tool? Redox Rep 2004; 9 (3): 145-152.
 
[40]  Anand H, Misro M, Sharma SB, Prakash S. Protective effects of Eugenia jambolana extract versus Nacetyl cysteine against cisplatin-induced damage in rat testis. Andrologia 2014; 10 (2): 291-297.
 
[41]  Watcho P, Kamtchouing P, Sokeng SD, Moundipa PF, Tantchou J, Essame JL. Androgenic effect of Mondia whitei roots in male rats. Asian J Androl 2004; 6 (3): 269-272.
 
[42]  Kasturi M, Manivannan B, Ahmed NR, Shaikh PD, Pattan KM. Changes in epididymal structure and function of albino rat treatedwith Azardirachta indica leaves. Indian J Expt Biol 1995; 33 (10): 725-729.
 
[43]  Yakubu MT, Akanji MA, Oladiji AT. Effects of oral administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats. J Ethnopharmacol 2008; 115 (2): 288-292.
 
[44]  Kamel KM, Abd El-Raouf OM, Metwally SA, Abd El-Latif HA, El-Sayed ME. Hesperidin and rutin, antioxidant citrus flavonoids, attenuate Cisplatin-induced nephrotoxicity in rats. J Biochem Mol Toxicol 2014; 28 (7): 312-319.
 
Show Less References

Article

The Effect of L-carnitine on Amethopterin-induced Toxicity in Rat Large Intestine

1Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt


Journal of Cancer Research and Treatment. 2014, 2(3), 55-63
DOI: 10.12691/jcrt-2-3-3
Copyright © 2014 Science and Education Publishing

Cite this paper:
Ehab Tousson, Mona Hegazy, Ezar Hafez, Alaa Abdullah Ahmed. The Effect of L-carnitine on Amethopterin-induced Toxicity in Rat Large Intestine. Journal of Cancer Research and Treatment. 2014; 2(3):55-63. doi: 10.12691/jcrt-2-3-3.

Correspondence to: Ehab  Tousson, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt. Email: toussonehab@yahoo.com

Abstract

Background: Amethopterin is a folic acid antagonist which used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. This study aimed to determine the possible protective effects of L-carnitine against Amethopterin induced large intestine toxicity. Methodology: A total 60 male albino rats were equally divided into six groups; the first and second groups were the control and L-carnitine groups respectively while the 3rd group was Amethopterin rat group; the 4th and 5th groups were co- and post- treated Amethopterin rat with L-carnitine respectively and the 6th group was self treated Amethopterin rat group. Results: Glutathione, catalase and total protein levels in Amethopterin and self-treated groups showed a significant decrease when compared with control group, while MDA levels in Amethopterin and self-treated groups showed a significant increase when compared with control group. Many of abnormalities as colonic epithelial cell damage in the form of epithelial separation, cellular loss, congestion of blood vessels, crypt hyperplasia and focal depletion of goblet cells were detected in large intestine tissues in Amethopterin rat group (Amethopterin and self-treated groups). A significant increase of the apoptotic protein p53 and a significant decrease in the antiapoptotic Bc1-2 proteins after Amethopterin injection when compared with control group was observed. Conclusions: Treatment (Co- and post-) with L-carnitine were improved the biochemical, histopathological and immunohistochemical alterations in large intestine that treated with Amethopterin.

Keywords

References

[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[
[1]  Cronstein BN. Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum 2004; 39: 1951-60.
 
[2]  Kimura E, Nishimura K, Sakata K, Oga S, Kashiwagi K, Igarashi K. Methotrexate differentially affects growth of suspension and adherent cells. Int J Biochem Cell Biol 2004; 36: 814-25.
 
[3]  Salzer WL, Winick NJ, Wacker P, Lu X, Devidas M, Shuster JJ. Plasma methotrexate, red blood cell methotrexate, and red blood cell folate values and outcome in children with precursor n B-acute lymphoblastic leukemia:a report from the children’s oncology group. J Pediatr Hematol Oncol 2012; 34: 1-7.
 
[4]  Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine. Biomed and Pharmacotherapy 2014; 68: 631-9.
 
[5]  Carneiro-Filho BA, Lima IP, Araujo DH, Cavalcante MC, Carvalho GH, Brito GA, Lima V, Monteiro SM, Santos FN, Ribeiro RA, Lima AA. Intestinal barrier function and secretion in methotrexate-induced rat intestinal mucositis. Dig Dis Sci 2004; 49: 65-72.
 
Show More References
[6]  Sener G, Demiralp EE, Etiner M, Ercan F, Yegen BC. Glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. European Journal of Pharmacology 2006; 542: 170-8.
 
[7]  Soares PM, Lopes LO, Mota JM, Belarmino-Filho JN, Ribeiro RA, de Souza MH. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats. Arq Gastroenterol 2011; 48: 80-85.
 
[8]  Wielinga P, Hooijberg JH, Gunnarsdottir S, Kathmann I, Reid G, Zelcer N, van der Born K, de Haas M, van der Heijden I, Kaspers G, Wijnholds J, Jansen G, Peters G, Borst P. The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res 2005; 65: 4425-30.
 
[9]  Laskin JD, Black AT, Jan YH, Sinko PJ, Heindel ND, Sunil V, Heck DE, Laskin DL. Oxidants and antioxidants in sulfur mustard-induced injury. Ann N Y Acad Sci 2010; 1203: 92-100.
 
[10]  Jahovic N, Cevik H, Sehirli AO, Yˇegen BC, Sener G. Melatonin prevents methotraxate- induced hepatorenal oxidative injury in rats. J Pineal Res 2003; 34: 282-7.
 
[11]  Cetin A, Kaynar L, Kocyigit I, Hacioglu SK, Saraymen R, Ozturk A, Sari I, Sagdic O. Role of grape seed extract on methotrexate induced oxidative stress in rat liver. American Journal of Chinese Medicine 2008; 36: 1-12.
 
[12]  Hemeida AR, Omar MM. Curcumin Attenuates Methotraxate-Induced Hepatic Oxidative Damage in Rats. Journal of the Egyptian Nat. Cancer Inst 2008; 20(2): 141-8.
 
[13]  Vardi N, Parlakpinar H, Ozturk F, Ates B, Gul M, Cetin A, Erdogan A, Otlu A. Potent protective effect of apricot and β-carotene on methotrexate induced intestinal oxidative damage in rats. Food and Chemical Toxicology 2008; 46: 3015-3022.
 
[14]  Vardi N, Parlakpinar H, Ates B, Cetin A, Otlu A. Antiapoptotic and antioxidant effects of beta-carotene against methotrexateinduced testicular injury. Fertil Steri 2009; 92: 2028-33.
 
[15]  Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. Biosci 2012; 37: 679-88.
 
[16]  Ozogula B, Kisaoglua A, Turanb MI, Altunerc D, Senerd E, Cetine N, Ozturk C. The effect of mirtazapine on methotrexate-induced toxicity in rat liver. Science Asia 2013; 39: 356-36.
 
[17]  Agarwal A, Said TM. Carnitines and male infertility. Reprod Biomed Online 2004; 8: 376-84.
 
[18]  Sinclair C, Gilchrist JM, Hennessey JV, Kandula M. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve 2005; 32: 357-9.
 
[19]  Ulvi H, Aygul R, Demir R. Effect of L-carnitine on diabetic neuropathy and ventricular dispersion in patients with diabetes mellitus. Turk J Med Sci 2010; 40: 169-75.
 
[20]  Chao HH, Liu JC, Hong HJ, Lin JW, Chen CH, Cheng TH. L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes. Int J Cardiol 2011; 146: 145-52.
 
[21]  Salama AF, Kasem SM, Tousson E, Elsisy MK. Protective role of L-carnitine and vitamin E on the kidney of atherosclerotic rats. Biomedicine & Aging Pathology 2012; 2: 212-5.
 
[22]  Salama A, Kasem S, Tousson E, Elsisy MK. L-carnitine and vitamin E alleviate reproductive toxicity caused by triton WR 1339 in male albino rats. Toxicology and Industrial Health; 2013.
 
[23]  Cayir K, Karadeniz A, Yildirim A, Kalkan Y, Karakoc A, Keles M. Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats. Cent Eur J Med 2009; 4: 184-91.
 
[24]  Pehlivan M, Coşkun A, Zengin A, Aslaner A, Yavuz T. Does L-carnitine increase serum TNF -α and IGF-1 during liver regeneration in the rat?. Turk J Med Sci 2009; 39: 875-80.
 
[25]  Al-Motabagani MA. Estudios histológico e histoquímico del efecto del metotrexato en el hígado de rata macho albina adulta. Int. J. Morphol 2006; 24(3): 417-22.
 
[26]  Aebi H. Catalase. In: Bergmeyer HU, (ed.) Methods of Enzymatic Analysis. New York: Academic Press 1984; pp: 673-84.
 
[27]  Saggu S, Kumar R. Modulatory effect of seabuckthorn leaf extract on oxidative stress parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery. J Pharm Pharmacol 2007; 59(12): 1739-45.
 
[28]  Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J.Lab. Clin. Med 1963; 61: 882-8.
 
[29]  Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J Biol Chem 1951; 193: 265-75.
 
[30]  Bancroft JD, Stevens GA. Theory and Practice of Histological Techniques. 2nd Ed. Churchill Livingstone, London 1990.
 
[31]  Sternberger LA. The unlabelled antibody peroxidase- antiperoxidase (PAP) method. In: “immunocytochemistry”, 2nd edn., (Cohen S, and McClusky RT.ed.). John Wiley and sons, New York 1979; pp: 104-69.
 
[32]  Tousson E, Alm-Eldeen A, El-Moghazy M. p53 and Bcl-2expression in response to boldenone induced liver cells injury. Toxicology and Industrial Health 2011; 27(8): 711-8.
 
[33]  Cunningham D, Morgan RJ, Mills PR. Functional and structural changes of the human proximal small intestine after cytotoxic therapy. J Clin Pathol 1985; 38: 265-70.
 
[34]  Phelen MJ, Taylor W, van Heyningen C, Williams E, Thompson RN.Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate. Clin Rheumatol 1993; 12: 223-25.
 
[35]  Zhang P, Li J, Liu Y, Chen X, Kang Q, Zhao J, Li W. Human neural stem cell transplantation attenuates apoptosis and improves neurological functions after cerebral ischemia in rats. Acta Anaesthesiol Scand 2009;53(9):1184-91.
 
[36]  Nagakubo J, Tomimatsu T, Kitajima M, Takayama H, Aimi N, Horie T. Characteristics of transport of fluoresceinated methotrexate in rat small intestine. Life Sci 2001; 69: 739-47.
 
[37]  Kolli RP, Seidman DN. Comparison of compositional and morphological atom-probe tomography analyses for a multicomponent Fe-Cu steel. Microsc Microanal 2007; 13: 272-84.
 
[38]  Wardill HR, Bowen JM, Gibson RJ. Chemotherapy-induced gut toxicity: are alterations to intestinal tight junctions pivotal?. Cancer Chemother Pharmacol 2012; 70: 627-35.
 
[39]  Rachmilewitz EA, Schrier S. Pathophysiology of β thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, editors. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge, UK: Cambridge University Press 2001; PP: 233-51.
 
[40]  Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med 2005; 353: 1135-46.
 
[41]  ALL C, Ertan B, Ergul BK, Bulent K. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med Sci Monit 2006; 12(8): 247-8.
 
[42]  Jahovic N, Sener G, Cevic H, Ersoy Y, Arbak S, Yegen BC. Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct 2004; 22: 169-78.
 
[43]  Vardi A, Bosviel R, Rabiau N, Adjakly M, Satih S, Dechelotte P. Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells. In Vivo 2010; 24: 393-400.
 
[44]  Atila K, Coker A, Sagol O, Coker I, Topalak O, Astarcioglu H, Karademir S, Astarcioglu I. Protective effects of carnitine in an experimental ischemia reperfusion injury. Clin Nutr 2002; 21: 309-13.
 
[45]  Derin N, Agac A, Bayram Z, Asar M, Izgut-Uysal VN. Effects of L-carnitine on neutrophil-mediated ischemia-reperfusion injury in rat stomach. Cell Biochem Funct 2006; 24: 437-42.
 
[46]  Babiak RM, Campello AP, Carnieri EG, Oliveira MB. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct 1998; 16: 283-93.
 
[47]  Fiocchi C. Inflammatory bowel disease: New insights into mechanisms of inflammation and increasingly customized approaches to diagnosis and therapy. Curr.Opin. Gastroentrol 2004; 20: 309-10.
 
[48]  Ciralik H, Bulbuloglu E, Cetinkaya A, Kurutas EB, Celik M, Polat A. Effects of N acetylcysteine on methotrexate induced small intestinal damage in rats. The Mount Sinai Journal of Medicine 2006; 73: 1086-92.
 
[49]  Tarasub N, Junseecha T, Tarasub C, Na Ayutthaya WD. Protective Effects of Curcumin, Vitamin C, or their Combination on Cadmium-Induced Hepatotoxicity. J Basic Clin Pharm 2012; 3: 273-81.
 
[50]  Stringer AM, Gibson RJ, Bowen JM, Logan RM, Yeoh AS, Keefe DM. Chemotherapy-induced mucositis: the role of gastrointestinal microflora and mucins in the luminal environment. J Support Oncol 2007; 5: 259-67.
 
[51]  Kalaiselvi, T, Panneersalvam C. Effect of L-carnitine on the status of lipid peroxidation and antioxidants in aging rats. J. Nutr. Biochem 1998; 9: 575-81.
 
[52]  Atroshi F, Rizzo A, Biese L, Veijalainen P, Saloniemi H, Sankari S, Andersson K. Fumonisin B1-induced DNA damage in rat liver and spleen: Effect of pretreatment with coenzyme Q10, L-carnitine, α-tocopherol and selenium. Pharmacol. Res 1999; 40: 459-67.
 
[53]  Arockia Rani PJ, Panneerselvam C. L-carnitine as a free radical scavenger in aging. Exp. Gerontol 2001; 36: 1713-26.
 
[54]  Vaux DL, Strasser A.The molecular biology of apoptosis. Proc Natl Acad Sci USA 1996; 93: 2239-44.
 
[55]  Nagatu S. Apoptosis by death factor. Cell 1997; 88: 355-65.
 
[56]  Tousson E, Beltagy DM, Abo Gazia M, Al-Behbehani B. Expressions of P53 and CD68 in mouse liver with Schistosoma mansoni infection and the protective role of silymarin. Toxicology and Industrial Health; 2012.
 
[57]  Diebold J, Baretton G, Felchner M, Meier W, Dopper K, Schmidt M, Lohrs U. Bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. Am J Clin Pathol 1996; 105: 341-34.
 
[58]  Augustyniak A, Skrzydlewska E. L-carnitine in the lipid and protein protection against ethanol-induced oxidative stress. Alcohol 2009; 43(3): 217-23.
 
Show Less References

Article

Recurrent Lung Abscesses during Chemotherapy in Non-neutropenic Patient with Limited Stage Small Cell Lung Cancer: A Case Report and Review

1The general organization for teaching hospitals, Cairo, Egypt


Journal of Cancer Research and Treatment. 2014, 2(3), 52-54
DOI: 10.12691/jcrt-2-3-2
Copyright © 2014 Science and Education Publishing

Cite this paper:
Mohammed Osman. Recurrent Lung Abscesses during Chemotherapy in Non-neutropenic Patient with Limited Stage Small Cell Lung Cancer: A Case Report and Review. Journal of Cancer Research and Treatment. 2014; 2(3):52-54. doi: 10.12691/jcrt-2-3-2.

Correspondence to: Mohammed  Osman, The general organization for teaching hospitals, Cairo, Egypt. Email: mmoneam@hotmail.com

Abstract

Background: Small cell lung cancer (SCLC) represents 14% of all lung cancer cases. The current standard of care for limited stage SCLC is the chemotherapy combination of EP (etoposide, cisplatin) with concomitant radiotherapy. Treatment protocol is tolerated well and is associated with few side effects.Case Description: 58 y.o. lady diagnosed to have limited stage SCLC in our institute in November 2013. She was planned for concomitant chemoradiotherapy (CCRT). She started initially on chemotherapy protocol EP. On day 12 of cycle 2, the patient complained of Fever, excessive cough. CT thorax showed newly developed peripherally situated pulmonary abscess. She was kept in with IV antibiotics, and her condition was improved thereafter. Then she was started on CCRT, with cycle 3 EP. On day 6 of her cycle 3, she developed fatigue, poor general condition, high fever, cough and neutropenia. She was admitted as neutropenic sepsis, with improvement of neutropenia after only 1 shot of short acting GCSF. Sputum culture showed Klebsiella pneumonia. CT Thorax showed new lung abscess in the Left ligula. She was treated by IV antibiotic for 10 days. Her condition was improving thereafter and she was returned back to radiotherapy, as well as Cycle 4 EP. Currently, she finished her treatment since 1 month with no complication related to treatment protocol. Discussion: Although few, studies attributed the reason for lung abscess development to leuconeutropenia in some patients, and to relatively large primary tumour size in other patients. Conclusion: Many reasons may explain the development of lung abscess in non-neutropenic patient including chemotherapy side effect, underlying chest condition, and relatively large primary tumour size.

Keywords

References

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[1]  Haller DG, Wagman LD, Camphausen KA, et al: Small-Cell Lung Cancer, Mesothelioma, and Thymoma, Chapter 4, Cancer Management: A Multidisciplinary Approach, 14th. Edition, 2012.
 
[2]  Fried DB, Morris DE, Poole C, et al: Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4837-4845, 2004.
 
[3]  Surendiran A, et al: Adverse drug reaction profile of cisplatin based chemotherapy regimen in a tertiary care hospital in India: An evaluation study. Indian J Pharmacol. Feb 2010; 42(1): 40-43.
 
[4]  Medscape.com @ http://reference.medscape.com/drug/platinol-aq-cisplatin-342108, http://reference.medscape.com/drug/vepesid-toposar-etoposide-342098,
 
[5]  Magaña E, Crowell RE: Radiation Pneumonitis Successfully Treated with Inhaled Corticosteroids, South Med J. 2003; 96(5).
 
Show More References
[6]  Hirshberg B, Sklair-Levi M, Nir-Paz R, et al: Factors predicting mortality of patients with lung abscess. Chest. 1999; 115 (3): 746-50.
 
[7]  Moreira JS, Camargo JJ, Felicetti JC, Goldenfun PR, et al: Lung abscess: analysis of 252 consecutive cases diagnosed between 1968 and 2004. Jornal brasileiro de pneumologia. 2006; 32 (2): 136-43.
 
[8]  Phernambucq CJ, Hartemink KJ, Smit EF, et al: Tumor cavitation in patients with stage III non-small-cell lung cancer undergoing concurrent chemoradiotherapy: incidence and outcomes. JOURNAL OF THORACIC ONCOLOGY. 2012; Vol. 7: Issue 8, 1271-1275.
 
[9]  Hansen SW, Aabo K, Osterlind K: Lung abscess in small cell carcinoma of the lung during chemotherapy and corticosteroids: an analysis of 276 consecutive patients. Eur J Respir Dis. 1986 Jan; 68(1):7-11.
 
[10]  Justice RL: Reported adverse side effects of cisplatin and etoposide. NDA 018057/Supplement081, 2013, www.FDA.org.
 
Show Less References

Article

Abrogation by Ginkgo Byloba Leaf Extract on Hepatic and Renal Toxicity Induced by Methotrexate in Rats

1Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt


Journal of Cancer Research and Treatment. 2014, 2(3), 44-51
DOI: 10.12691/jcrt-2-3-1
Copyright © 2014 Science and Education Publishing

Cite this paper:
Ehab Tousson, Zeinab Atteya, Afaf El-Atrash, Ola I. Jeweely. Abrogation by Ginkgo Byloba Leaf Extract on Hepatic and Renal Toxicity Induced by Methotrexate in Rats. Journal of Cancer Research and Treatment. 2014; 2(3):44-51. doi: 10.12691/jcrt-2-3-1.

Correspondence to: Ehab  Tousson, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt. Email: toussonehab@yahoo.com

Abstract

Methotrexate (MTX) is used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. The present study aimed to examine the possible modifying effects of Ginkgo biloba leaf extract (GLE) against hepatic and renal toxicity induced by MTX in rats. A total 60 male albino rats were equally divided into six groups; the first and second groups were the control and GLE groups respectively while the 3rd group was MTX rat group; the 4th and 5th groups were Co- and post treated MTX rat with GLE respectively and the 6th group was MTX self treated rat group. Serum GPT, GOT, urea, creatinine, uric acids and MDA levels in MTX group showed a significant increase when compared with control group, in contrast, MTX-treated group also exhibited a significant decrease in liver antioxidant machinery represented by GSH, catalase, SOD and total protein. Administration of GLE combined with MTX improved the liver and kidney damages induced by MTX. Histopathological and evidence, together with observed CD68 immunoreactivity, supported the detrimental effect of MTX and the ameliorating effect of GLE on liver and kidney toxicities. GLE possessed various protective mechanisms against MTX-induced liver and kidney toxicity throughout Co- and post- treatment. We can conclude that Co-treatment with GLE has beneficial properties and can reduce the liver and kidney damages and toxicity induced by MTX.

Keywords

References

[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[
[1]  Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to Amethopterin-induced lung injury and ameliorating role of L-carnitine. Biomed and pharmacology 2014.
 
[2]  West SG. Methotrexate hepatoxicity. Rheum Dis Clin North Am 1997; 23: 883-915.
 
[3]  Yozai K, Shikata K, Sasaki M, Tone A, Ohga S, Usui H. Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions. J Am Soc Nephrol 2005; 16: 3326-3338.
 
[4]  ALL C, Ertan B, Ergul BK, Bulent K. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med Sci Monit 2006; 12 (8): 247-248.
 
[5]  Ozogula B, Kisaoglua A, Turanb M.I, Altunerc D, Senerd E, Cetine N, Ozturk C. The effect of mirtazapine on methotrexate-induced toxicity in rat liver. Science Asia 2013; 39: 336-356.
 
Show More References
[6]  Johovic N, Cevik H, Sehirli OA, Yegen BÇ, Şener G. Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. Journal of Pineal Research 2003; 34, 282-287.
 
[7]  Cetin A, Kaynar L, Kocyigit I, Hacioglu S.K, Saraymen R, Ozturk A, Chan ES, Montesinos MC, Fernandez P. Adenosine A (2A) receptors play a role in the pathogenesis of hepatic cirrhosis. Br J Pharmacol 2006; 148 (8): 1144-1155.
 
[8]  Hemeida A.R, Omar M.M. Curcumin Attenuates Methotraxate-Induced Hepatic Oxidative Damage in Rats. Journal of the Egyptian Nat Cancer Inst 2008; 20 (2): 141-148.
 
[9]  Vardi N, Parlakpinar H, Ozturk F, Ates B, Gul M, Cetin A, Erdogan A, Otlu A. Potent protective effect of apricot and β-carotene on methotrexate induced intestinal oxidative damage in rats. Food and Chemical Toxicology 2008; 46: 3015-3022.
 
[10]  Vardi N, Parlakpinar H, Ates B, Cetin A, Otlu A. Anti apoptotic and antioxidant effects of beta-carotene against methotrexate-induced testicular injury. Fertil Steri 2009; 92: 2028-2033.
 
[11]  Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. J Biosci 2012; 37: 679-688.
 
[12]  Stickel F, Schuppan D. Herbal medicine in the treatment of liver diseases. Dig Liver Dis 2007; 39: 230-293
 
[13]  Abad MJ, Bedoya LM, Bermejo P. An update on drug interactions with the herbal medicine Ginkgo biloba. Current Drug Metabolism 2010; 11: 171-181.
 
[14]  Sakr SA, Abo-El-Yazid SM. Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats. Toxicology and Industrial Health 2012; 28 (10): 876-885.
 
[15]  Sakeran MI, Zidan N, Rehman H, Aziz AT, Saggu S. Abrogation by Trifolium alexandrinum root extract on hepatotoxicity induced by acetaminophen in rats. Redox Rep 2014; 19 (1): 26-33.
 
[16]  Elsabagh S, Hartley D.E, Ali O, Williamson E.M, File S.E. Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers. Psychopharmacology 2005; 179: 437-446.
 
[17]  Altiok N, Ersoz M, Karpuz V, Koyuturk M. Ginkgo biloba extract regulates differentially the cell death induced by hydrogen peroxide and simvastatin. Neurotoxicology 2006; 27: 158-163.
 
[18]  Kalisz O, Wolski T, Gerkowicz M. Miłorząb japoński (Ginkgo biloba) i jego preparaty wterapii zabur zeńkrążenia mózgowego i obwodowego [Ginkgo biloba (Ginkgo biloba) and its preparations in therapy of cerebral and peripheral circulation disorders]. Ann. Univ. Mariae Curie-Skłodowska 2006; 61 (2): 11-17.
 
[19]  Abdel-Kader R, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A, Müller WE. Stabilization of mitochondrial function by Ginkgo biloba extract. Pharmacol Res 2007; 56 (6): 493-502.
 
[20]  Liu JJ, Ching LM, Goldthorpe M, Sutherland R, Baguley BC, Kirker JA, McKeage MJ. Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours. Cancer Chemother Pharmacol 2007; 59: 661-669.
 
[21]  Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci 2008; 73 (R) 14-19.
 
[22]  Kobus J, Flaczyk E, Siger A, Nogala-Kalucka M, Korczak J, Pegg R.B. Phenolic compounds and antioxidant activity of extracts of Ginkgo leaves. Eur J Lipid Sci Technol 2009; 111 (11): 1150-1160.
 
[23]  Cha´vez-Morales RM, Jaramillo-Jua´rez F, Posadas del Rı´o FA, Reyes-Romero MA, Rodrı´guez-Va´zquez ML, Martı´nezSaldan˜a MC. Protective effect of Ginkgo bilobaextract on liver damage by a single dose of CCl4in male rates. Hum Exp Toxicol 2011; 30: 209-216.
 
[24]  Sener G, Eksioglu-Demiralp E, Cetiner M, Ercan F, Yegen BC. Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol 2006; 542 (33): 170-178.
 
[25]  Yozai K, Shikata K, Sasaki M, Tone A, Ohga S, Usui H. Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions. J Am Soc Nephrol,2005; 16: 3326-3338.
 
[26]  Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Amer J Clin Pathol 1957; 28: 56-63.
 
[27]  Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chim Acta 1971; 31: 87-96.
 
[28]  Fawcett J.K, Scott J.E. A rapid and precise method for the determination of urea. J Clin Path 1960; 113: 156.
 
[29]  Bowers LD, Wong ET. Kinetic serum creatinine assays. II. A critical valuation and review. Clin Chem 1980; 26 (5): 555-561.
 
[30]  Mesbah L, Soraya B, Narimane S, Jean PF. Protective effect of flavonoides against the toxicity of vinblastine cyclophosphamide and paracetamol by inhibition of lipid- peroxidation and increase of liver glutathione. Haema 2004; 7: 59-67.
 
[31]  Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882-888.
 
[32]  Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J. Biol. Chem. 1951; 193: 265-275.
 
[33]  Tsuyosh P, James KB. A simplified method of quantitating Protein using the Buiret and phenol reagents, Anal Biochem 1978; 86: 193-200.
 
[34]  Bancroft JD, Stevens A. Theory and Practice of Histological Technique. 3rd Ed. Churchill Living stone. Edinburgh, London benefits in Stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. J Psychopharmacol 1990; 19: 173-181.
 
[35]  Balk RA. Methotrexate-induced lung injury. UpT o Date, 2006. Available at: www.uptodate.com. Accessed 8 May 2006.
 
[36]  Kremer JM. Major side effects of methotrexate. UpToDate, 2006. Available at: www.uptodate.com. Accessed 8 May 2006.Laboratory Medicine. Chapter 66. Lexi-Comp Inc.
 
[37]  Genestier L, Paillot R, Quemeneur L, Izeradjene K, Revillard JP. Mechanisms of action of methotrexate. Immunopharmacology 2000; 47: 247-257.
 
[38]  Walling J. From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Investigational New Drugs 2006; 24: 37-77.
 
[39]  Wielinga P, Hooijberg JH, Gunnarsdottir S. The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res 2005; 65: 4425-4430.
 
[40]  Maiti R, Jana D, Das U.K, Ghosh D. Antidiabetic effect of aqueous effect of seed of Tamarindus indica in streptozotocininduced diabetic rats. J Ethnopharmacol 2004; 92: 85-91.
 
[41]  Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol 2008; 73 (2): 399-409.
 
[42]  Vardi A, Bosviel R, Rabiau N, Adjakly M, Satih S, Dechelotte P. Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells. In Vivo 2010; 24: 393-400.
 
[43]  Drotman R, Lawhan G. Serum enzymes are indications of chemical induced liver damage. Drug Chem Toxicol 1978; 1: 117-163.
 
[44]  Sakeran M.I, Zidan N, Rehman H, Aziz AT, Saggu S. Abrogation by Trifolium alexandrinum root extract on hepatotoxicity induced by acetaminophen in rats. Redox Rep 2014; 19 (1): 26-33.
 
[45]  Saggu S, Kumar R. Modulatory effect of seabuckthorn leaf extract on oxidative stress parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery. J Pharm Pharmacol 2007; 59 (12): 1739-1745.
 
[46]  Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol 2007; 109: 214-218.
 
[47]  Kadikoylu G, Bolaman Z, Demir S, Balkaya M, Akalin N, Enli Y. The effects of desferrioxamine on cisplatininduced lipid peroxidation and the activities of antioxidant enzymes in rat kidneys. Hum Exp Toxicol 2004; 23: 29-34.
 
[48]  Klukowska L, Nadulska A, Dyba S. The influence of cisplatinum and goserelinum on the magnesium and calcium level in rat serum. Ann Univ Mariae Curie Sklodowska [Med]. 2001; 56: 483-486.
 
[49]  Saad MF, Greco S, Osei K, Lewin AJ, Edwards C, Nunez M, Reinhardt RR. Ragaglitazar improves glycemic control and lipid profile in type 2 diabetic subjects: a 12-week, double-blind, placebocontrolled dose-ranging study with an open pioglitazone arm. Diabetes 2004; 27: 1324-1329.
 
[50]  Thabrew M, Joice P. A comparative study of the efficacy of Pavetta indica and Osbeckia octanda in the treatment of liver dysfunction. Planta Med 1987; 53 (3): 239-241.
 
[51]  Kolli VK, Abraham P, Rabi S. Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat. Archives of Toxicology 2008; 82 (10): 763-770.
 
[52]  Jahovic N, Sener G, Cevic H, Ersoy Y, Arbak S, Yegen BC. Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Function 2004; 22-28.
 
[53]  Cetiner M, Sener G, Sehirli AO, Eksioglu-Demiralp E, Ercan F, Sirvanci S, Gedik N, Akpulat S, Tecimer T, Yegen BC. Taurine protects against methotrexate-induced toxicity and inhibits leucocyte death. Toxicol Appl Pharmacol 2005; 209 (1): 39-50.
 
[54]  Sener G, Eksioglu-Demiralp E, Cetiner M, Ercan F, Yegen BC. Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol 2006; 542 (33): 170-178.
 
[55]  Vardi A, Bosviel R, Rabiau N, Adjakly M, Satih S, Dechelotte P. Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells. In Vivo. 2010; 24: 393-400.
 
[56]  Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem 1995; 64: 97-112.
 
[57]  Ciralik H, Bulbuloglu E, Cetinkaya A, Kurutas E.B, Celik M, Polat A. Effects of N acetylcysteine on methotrexate induced small intestinal damage in rats. The Mount Sinai Journal of Medicine. 2006; 73: 1086-1092.
 
[58]  Lone I.A, Kaur G, Athar M, Alam M.S. Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response. Food Chem Toxicol 2007; 45: 1821-1829.
 
[59]  Babiak RM, Campello AP, Carnieri EG, Oliveira M.B. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Function 1998; 16: 283-293.
 
[60]  Prahalathan C, Selvakumar E, Varalakshmi P. Protective effect of lipoic acid on adriamycin-induced testicular toxicity. Clinica Chimica Acta 2005; 360: 160-166.
 
[61]  O’Rourke RA, Eckert GE. Methotrexate-induced hepatic injury in an adult A case report. Arch Int Med 1964; 113: 191-194.
 
[62]  Ros S, Juanola X, Condom E, Canas C, Riera J, Guardiola J, Del Blanco J, Rebasa P, Valverde J, Roig-Escofet O. Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy. Scand J Rheumatol 2002; 31 (6): 330-336.
 
[63]  Hytiroglou P, Tobias H, Saxena R, Abramidou M, Papadimitriou CS, Theise ND. The canals of hering might represent a target of methotrexate hepatic toxicity. Am J Clin Pathol 2004; 121 (3): 324-329.
 
[64]  Horie T, Li T, Ito K, Sumi S, Fuwa T. Aged garlic extract protects against methotrexate-induced apoptotic cell injury of IEC-6 cells. J Nutr 2006; 53: 239-241.
 
Show Less References