Evidence Against Protective Role of Sex Hormone Estrogen in Cisplatin"‘Induced Nephrotoxicity in Ovarectomized Rat Model

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Keywords:

Cisplatin, estrogen, nephrotoxicity, ovarectomized rat

Abstract

Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well"‘documented; but its nephron"‘protective effect against CP"‘induced nephrotoxicity is not completely understood. Materials and Methods: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1"‘3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. Results: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP"‘treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen"‘treated groups (Groups 1"‘3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r2 = 0.63, P < 0.01). Conclusion: Estrogen is not nephron"‘protective against CP"‘induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen"‘induced oxidative stress in the kidney, which may promote the nephrotoxicity.

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Published

2018-08-09

How to Cite

Pezeshki, Z., Nematbakhsh, M., Nasri, H., Talebi, A., Pilehvarian, A., Safari, T., Eshraghi"‘Jazi, F., Haghighi, M., & Ashrafi, F. (2018). Evidence Against Protective Role of Sex Hormone Estrogen in Cisplatin"‘Induced Nephrotoxicity in Ovarectomized Rat Model. Toxicology International, 20(1), 43–47. Retrieved from http://www.informaticsjournals.com/index.php/toxi/article/view/21701

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Section

Original Research
Received 2018-08-08
Accepted 2018-08-08
Published 2018-08-09

 

References

McGuinness SJ, Ryan MP. Mechanism of cisplatin nephrotoxicity in rat renal proximal tubule suspensions. Toxicol in vitro 1994;8:1203"‘12.

Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel) 2010;2:2490"‘518.

Santos NA, Catí£o CS, Martins NM, Curti C, Bianchi ML, Santos AC.Cisplatin"‘induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 2007;81:495"‘504.

Ajith TA, Abhishek G, Roshny D, Sudheesh NP. Co"‘supplementation of single and multi doses of vitamins C and E ameliorates cisplatin"‘induced acute renal failure in mice. Exp Toxicol Pathol 2009;61:565"‘71.

Antunes LM, Darin JD, Bianchi MD. Protective effects of vitamin c against cisplatin"‘induced nephrotoxicity and lipid peroxidation in adult rats: A dose"‘dependent study. Pharmacol Res 2000;41:405"‘11.

Appenroth D, Fröb S, Kersten L, Splinter FK, Winnefeld K.Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol 1997;71:677"‘83.

Atasayar S, Gürer"‘Orhan H, Orhan H, Gürel B, Girgin G, Ozgüneş H.Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin"‘induced nephrotoxicity in rats. Exp Toxicol Pathol 2009;61:23"‘32.

Behling EB, Sendí£o MC, Francescato HD, Antunes LM, Costa RS, Bianchi Mde L. Comparative study of multiple dosage of quercetin against cisplatin"‘induced nephrotoxicity and oxidative stress in rat kidneys. Pharmacol Rep 2006;58:526"‘32.

Maliakel DM, Kagiya TV, Nair CK. Prevention of cisplatin"‘induced nephrotoxicity by glucosides of ascorbic acid and alpha"‘tocopherol. Exp Toxicol Pathol 2008;60:521"‘7.

Saleh S, Ain"‘Shoka AA, El"‘Demerdash E, Khalef MM.Protective effects of the angiotensin II receptor blocker losartan on cisplatin"‘induced kidney injury. Chemotherapy 2009;55:399"‘406.

Bodnar L, Wcislo G, Gasowska"‘Bodnar A, Synowiec A, Szarlej"‘WcisÅ‚o K, Szczylik C. Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelialovarian cancer after cisplatin and paclitaxel chemotherapy: A randomised phase II study. Eur J Cancer 2008;44:2608"‘14.

Kang DH, Yu ES, Yoon KI, Johnson R. The impact of gender on progression of renal disease: Potential role of estrogen"‘mediated vascular endothelial growth factor regulation and vascular protection. Am J Pathol 2004;164:679"‘88.

Silbiger SR, Neugarten J. The role of gender in the progression of renal disease. Adv Ren Replace Ther 2003;10:3"‘14.

Wei Q, Wang MH, Dong Z. Differential gender differences in ischemic and nephrotoxic acute renal failure. Am J Nephrol 2005;25:491"‘9.

Wongtawatchai T, Agthong S, Kaewsema A, Chentanez V.Sex"‘related differences in cisplatin"‘induced neuropathy in rats.J Med Assoc Thai 2009;92:1485"‘91.

Stakisaitis D, Dudeniene G, JankÅ«nas RJ, Grazeliene G, Didziapetriene J, Pundziene B. Cisplatin increases urinary sodium excretion in rats: Gender"‘related differences. Medicina (Kaunas) 2010;46:45"‘50.

He Q, Liang CH, Lippard SJ. Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin. Proc Natl Acad Sci U S A 2000;97:5768"‘72.

Beleh MA, Lin YC, Brueggemeier RW. Estrogen metabolism in microsomal, cell, and tissue preparations of kidney and liver from Syrian hamsters. J Steroid Biochem Mol Biol 1995;52:479"‘89.

But terworth M, Lau SS, Monks TJ. 2"‘Hydroxy"‘ 4"‘glutathion"‘S"‘yl"‘17beta"‘estradiol and 2"‘hydroxy"‘1"‘ glutathion"‘S"‘yl"‘17beta"‘estradiol produce oxidative stress and renal toxicity in an animal model of 17beta"‘estradiol"‘mediated nephrocarcinogenicity. Carcinogenesis 1998;19:133"‘9.

Roy D, Liehr JG. Target organ"‘specific inactivation of drug metabolizing enzymes in kidney of hamsters treated with estradiol. Mol Cell Biochem 1992;110:31"‘9.

Cho JJ, Cadet P, Salamon E, Mantione K, Stefano GB. The nongenomic protective effects of estrogen on the male cardiovascular system: Clinical and therapeutic implications in aging men. Med Sci Monit 2003;9:RA63"‘8.

Choudhry MA, Chaudry IH. 17beta"‘Estradiol: A novel hormone for improving immune and cardiovascular responses following trauma"‘hemorrhage. J Leukoc Biol 2008;83:518"‘22.

Dubey RK, Jackson EK. Cardiovascular protective effects of 17beta"‘estradiol metabolites. J Appl Physiol 2001;91:1868"‘83.

Mendelsohn ME. Protective effects of estrogen on the cardiovascular system. Am J Cardiol 2002;89 Suppl 1:12"‘7.

Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999;340:1801"‘11.

Nematbakhsh M, Ghadesi M, Hosseinbalam M, Khazaei M, Gharagozloo M, Dashti G, et al. Oestrogen promotes coronary angiogenesis even under normoxic conditions. Basic Clin Pharmacol Toxicol 2008;103:273"‘7.

Nematbakhsh M, Khazaei M. The effect of estrogen on serum nitric oxide concentrations in normotensive and DOCA Salt hypertensive ovariectomized rats. Clin Chim Acta 2004;344:53"‘7.

Ammer U, Natochin Yu, David C, Rumrich G, Ullrich KJ. Cisplatin nephrotoxicity: Site of functional disturbance and correlation to loss of body weight. Ren Physiol Biochem 1993;16:131"‘45.

Endo Y, Kanbayashi H. Modified rice bran beneficial for weight loss of mice as a major and acute adverse effect of Cisplatin.Pharmacol Toxicol 2003;92:300"‘3.

Miya T, Goya T, Yanagida O, Nogami H, Koshiishi Y, Sasaki Y. The influence of relative body weight on toxicity of combination chemotherapy with cisplatin and etoposide. Cancer Chemother Pharmacol 1998;42:386"‘90.

Deegan PM, Nolan C, Ryan MP, Basinger MA, Jones MM, Hande KR. The role of the renin"‘angiotensin system in cisplatin nephrotoxicity. Ren Fail 1995;17:665"‘74.

Goren MP. Cisplatin nephrotoxicity affects magnesium and calcium metabolism. Med Pediatr Oncol 2003;41:186"‘9.

Saad SY, Najjar TA, Daba MH, Al"‘Rikabi AC. Inhibition of nitric oxide synthase aggravates cisplatin"‘induced nephrotoxicity: Effect of 2"‘amino"‘4"‘methylpyridine. Chemotherapy 2002;48:309"‘15.

Saleh S, El"‘Demerdash E. Protective effects of L"‘arginine against cisplatin"‘induced renal oxidative stress and toxicity: Role of nitric oxide. Basic Clin Pharmacol Toxicol 2005;97:91"‘7.

Pabla N, Murphy RF, Liu K, Dong Z. The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol 2009;296:F505"‘11.

Qian W, Nishikawa M, Haque AM, Hirose M, Mashimo M, Sato E, et al. Mitochondrial density determines the cellular sensitivity to cisplatin"‘induced cell death. Am J Physiol Cell Physiol 2005;289:C1466"‘75.

Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: A review. Am J Med Sci 2007;334:115"‘24.

Ha CS, Joo BS, Kim SC, Joo JK, Kim HG, Lee KS. Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovary. J Obstet Gynaecol Res 2010;36:789"‘95.

Kauser K, Rubanyi GM. Gender difference in bioassayable endothelium"‘derived nitric oxide from isolated rat aortae. Am J Physiol 1994;267:H2311"‘7.

Kauser K, Rubanyi GM. Gender difference in endothelial dysfunction in the aorta of spontaneously hypertensive rats.Hypertension 1995;25:517"‘23.

Adams C, McCarthy HO, Coulter JA, Worthington J, Murphy C, Robson T, et al. Nitric oxide synthase gene therapy enhances the toxicity of cisplatin in cancer cells. J Gene Med 2009;11:160"‘8.

Jung M, Hotter G, Viñas JL, Sola A. Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury. Toxicol Appl Pharmacol 2009;234:236"‘46.

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