Study on nephroprotective effect of Ebselen in cisplatin induced renal damage in rats
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20174381Keywords:
Amifostine, Cisplatin, Ebselen, Nephro-protective effectAbstract
Background: Renal dysfunction arises as a result of exposure to medicines, industrial or environmental chemicals. Cisplatin is a major antineoplastic drug used for the treatment of solid tumors. Its chief dose limiting side effect is nephrotoxicity; 20% of patients receiving high-dose cisplatin have severe renal dysfunction. Ebselen a promising antioxidant, was used to explore the nephroprotective effect.
Methods: The rats were divided into five groups; each group consisting of 6 animals. The experimental design included one control group and four experimental groups. The study was carried out for a period of 7 wks. The test drug Ebselen in group 4 and 5 and the reference standard drug Amifostine in group 3 was administered once a week intraperitoneally for 5 weeks. Nephrotoxicity was induced by cisplatin (5mg/kg IP) in the 6th week, following this the drug Amifostine in group 3 and Ebselen in group 4 and 5 will be continued twice a day for 5 consecutive days post induction. Urine samples were collected and sent for determination of urine creatinine and albumin.
Results: The Urine creatinine level and albumin level estimation in group II show significant renal damage as compared to control group. The statistical reduction in urine creatinine and urine albumin level in Ebselen treated group I (10mg/kg), Ebselen group V (20mg/kg) as compared to Cisplatin group II show a potential reduction in renal damage. Ebselen treated group V showed a reduction in urine creatinine and urine albumin as same as in group III.
Conclusions: This study brings to a close that Ebselen lessens Cisplatin induced renal damage.
References
Nasri, H. World kidney day. Chronic kidney disease and aging: A global health alert. Iran J Public Health 2014;43:126-7.
Schieppati A, Remuzzi G. Chronic renal diseases as a public health problem: Epidemiology, social, and economic implications. Kidney Int. Suppl. 2005.
Finlay S, Bray B Lewington AJ, Hunter-Rowe CT, Banerjee A, Atkinson JM, et al. Identification of risk factors associated with acute kidney injury in patients admitted to acute medical units. Clin Med. 2013;13:233-8.
Taber SS, Mueller BA. Drug-associated renal dysfunction. Crit. Care Clin. 2006;22:357-74.
Azad GK, Tomar RS. Ebselen, a promising antioxidant drug: mechanism of action and targets of biological pathways. Mol Biol Rep: 2014.
Sies H. Free Radic. Biol Med. 1993;14:313-23.
Sies H. Methods Enzymol. 1994;234:476-82.
Schewe T. Gen Pharmacol. 1995;26:1153-69.
Nakamura Y, Feng Q, Kumagai T, Torikai K, Ohigashi H, Osawa T, Noguchi N, Niki E, Uchida K. J. Biol. Chem. 2002;277:2687-94.
Zhang M, Nomura A, Uchida Y, Lijima H, Sakamoto T, Lishii Y, et al. Free Radic. Biol Med. 2002;32:454-64.
CPCSEA, Guidelines for laboratory animal, facility, the committee for the purpose of control and supervision of experiments on animals, Chennai. 2004.
Tudor G, Aguilera A, Halverson DO, Laing ND, Sausville EA. Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death and Differentiation. 2000 Jun 1;7(6):574.
Henkels KM, Turchi JJ. Cisplatin-induced apoptosis proceeds by caspase-3-dependent and -independent pathways in cisplatin-resistant and -sensitive human ovarian cancer cell lines. Cancer Res. 1999;59:3077-83.
Takeda M, Kobayashi M, Shirato I, Endou H. Involvement of macromolecule synthesis, endonuclease activation and c-fos expression in cisplatin-induced apoptosis of mouse proximal tubule cells. Toxicol Lett. 1998;94:83-92.
Marzatico F, Porta C, Moroni M, Bertorelli L, Borasio E, Finotti N, et al. In vitro antioxidant properties of amifostine (WR-2721, Ethyol). Cancer Chemotherapy and Pharmacology. 2000 Jan 16;45(2):172-6.
Müller A, Cadenas E, Graf P, Sies H. A novel biologically active seleno-organic compound-1: Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen). Biochemical Pharmacology. 1984 Oct 15;33(20):3235-9.
Wendel A, Fausel M, Safayhi H, Tiegs G, Otter R. A novel biologically active seleno-organic compound- II: Activity of PZ 51 in relation to Glutathione Peroxidase. Biochemical Pharmacology. 1984 Oct 15;33(20):3241-5.
Müller A, Gabriel H, Sies H, Terlinden R, Fischer H, Römer A. A novel biologically active selenooorganic compound-VII: Biotransformation of ebselen in perfused rat liver. Biochemical Pharmacology. 1988 Mar 15;37(6):1103-9.
