ROLE OF EBSELEN, A SELENOORGANO COMPOUND IN CISPLATIN INDUCED NEPHROTOXICITY IN WISTAR RATS


Praharsheta A. M., Vanitha Samuel, Nirmala P.

Abstract


Objective: Nephrotoxicity is encountered worldwide, irrespective of several factors, but drug induced nephrotoxicity is a complication that is attributed to the high dose and even low dose of drugs. Cisplatin, a platinum complex used in the chemotherapy of several solid tumors was found to have a chief dose limiting side effect namely nephrotoxicity, which occurred due to lipid peroxidation and formation of reactive oxygen species. Ebselen, a eleno organo compound, a glutathione peroxidase mimic with anti-oxidant activity was used in our study to evaluate its nephro protective potential.

Methods: Male wistar rats, 6-8 wks old, weighing 180-200 grams were used for the study, which was carried out for a period of 7 wks. Animals were divided into five groups; each group consisting of 6 animals. Group I served as control. Group IV & V received the test drug Ebselen in doses of 10 mg/kg & 20 mg/kg respectively. Group III received Amifostine at 50 mg/kg. The drugs were administered once a week intraperitoneally for 5 wks. Nephrotoxicity was induced at a dose of 5 mg/kg single dose for groups II to V in the 6th wk and the drugs in group III, IV & V continued for 5 days post induction. In the 7th wk blood samples were collected for biochemical analysis and kidney tissues for histopathological study.

Results: The serum urea, creatinine levels were significantly increased in Cisplatin group compared to other groups. The estimation of antioxidant levels (catalase, superoxide dismutase and glutathione peroxidise) was significantly decreased in cisplatin group and increased in other groups. The estimation of Malondialdehyde an indicator of lipid peroxidation was significantly increased in group II and decreased in drug treated group. Histopathology results of animals treated with Cisplatin showed inflammatory changes such as tubular degeneration, edema, and necrosis, infiltration of cells in tubular interstitum, mild intertubular hemorrhage and atrophy of glomeruli which was severe in group II. Some changes were also observed in Group III, IV and V animals but with less severity.

Conclusion: The result of our study effectively proves the antioxidant potential of Ebselen in ameliorating Cisplatin induced nephrotoxicity.

Keywords: Cisplatin, Ebselen, Nephrotoxicity, Malondialdehye, Amifostine.

| PDF | HTML |

References


Yao. Cisplatin toxicity, Acute renal insufficiency; Apoptosis, Reactive oxygen species. Am J Med Sci 2007;334(2):115-24.

Yamate J, Sato K, Ide M, Nakanishi M, Kuwamura M, Sakuma S, et al. Participation of different macrophage populations and myofibroblastic cells in chronically developed renal interstitial fibrosis after Cisplatin-induced renal injury in rats. Dev Pathol 2002;39:322-33.

Shi Y, Inoue S, Shinozaki R, Fukue K, Kougo T. Release of cytokines from human umbilical vein endothelial cells treated with platinum compounds in vivo. Jpn J Cancer Res 1998;89:757-67.

Muller A, Cadenas E, Graf P Nad, Sies HA. Novel biologically active seleno-organic compound I-Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ51(ebselen). Biochem Pharmacol 1984;33:3235-9.

Wendel A, Fausel M, Safayhi H, Tiegs G, Otter RA. Biologically active selenoorganic compound II. Activity PZ51 in relation to glutathione peroxidase. Biochem Pharmacol 1984;33:3241-45.

Fischer H, Dereu N. Mechanism of the catalytic reduction of hydroperoxides by ebselen: A selenium-77 NMR study. Bwi Soc Chim Beig 1987;96:757-68.

Chew P, Yuen DY, Stefanovic N, Pete J, Coughian MT, Jandeleit-Dahm KA, et al. Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/Gpx 1-double knockout mouse. Diabetes 2010;59(12):3198-207.

Ishii Y, Hashimoto K, Nomura A, Sakamoto T, Uchida Y, Sagai M, et al. Ebselen decreases ozone-induced pulmonary inflammation in rats. Lung 2000;178(4):225-34.

Pratta MA, Ackerman NR. Arner ec effect of ebselen on IL-1 induced attenuation in cartilage metabolism. Inflammation Res 1998;47(3):115-21.

Johnsen-Soriano S, Genoves JM, Romero B, Garcia-Delpech S, Muriach M, Sancho-Tello M, et al. Chronic ethanol feeding induces oxidative stress in the rat retina: treatment with the antioxidant ebselen. Arch Soc Esp Oftalmol 2007;82(12):757-62.

Zhang M, Nomura A, Uchida Y, Iijima H, Sakamoto T, Iishii Y, et al. Effect of ebselen on ca2+transport in mitochondria. Redox Rep 2002;5(6):359-63.

Azad GK, Balkrishna SJ, Sathish N, Kumar S, To mal Rs. Multifactorial Ebselen drug functiona through the activation of DNA damage respose and alterations in nuclear proteins. Biochem Pharmacol 2012;83(2):296-303.

Allain CC, Poon Ls, Chan CS, Richmond W. FU PC Enzymatic determination of total cholesterol. Clin Chem 1974;20(4):470-5.

Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21(2):130-2.

Sinha Ak. Colorimetric assay of catalase. Anal Biochem 1972;47(2):389-94.

Boogaard PJ, Lempers EL, Mulder GJ, Meerman JHN. 4-methyl thiobenzoic acid reduce cisplatin nephrotoxicity in rats witout compromising anti-tumour activity. Biochem Pharmacol 1991;41:1997-2003.

Wendel A. Enzymatic basis of detoxication. Vol. 1. Academic press NY; 1980. p. 333.

Nakano S, Gemba M. Potentiation of Cisplatin-induced lipid peroxidation in kidney cortical slices by glutathione depletion. Jpn J Pharmacol 1988;50:87-92.

Zhang JG, Lind up WE. Role of mitochondria in Cisplatin induced oxidative damage wxhibites by rat cortical slices. Biochem Pharmacol 1993;43:2215-22.

Sinet PM, Carper P. Inactivation of the human CuZn-superoxide dismutase during exposure to O2 and H2O2. Arch Biochem Biophys 1981;212:411-6.




About this article

Title

ROLE OF EBSELEN, A SELENOORGANO COMPOUND IN CISPLATIN INDUCED NEPHROTOXICITY IN WISTAR RATS

Date

10-04-2015

Additional Links

Manuscript Submission

Journal

International Journal of Current Pharmaceutical Research
Vol 7, Issue 2, 2015 Page: 57-59

Online ISSN

0975-7066

Statistics

135 Views | 16 Downloads

Authors & Affiliations

Praharsheta A. M.
Post graduate Department of Pharmacology Rajah Muthaiah Medical College, Annamalai University, Chidambaram-607001, and Tamilnadu, India

Vanitha Samuel
Professor Department of Pharmacology Rajah Muthiah Medical College, Annamalai University, Chidambaram-607001, Tamilnadu, India

Nirmala P.
Professor& Head Department of Pharmacology Rajah Muthaiah Medical College, Annamalai University, Chidambaram 607001, Tamilnadu, India


Refbacks

  • There are currently no refbacks.