The protective effect of Tribulus terrestris and it's combination with, Boerhaavia diffusa and Terminalia chebula against cisplatin induced nephrotoxicity in rats

[Speaker] Harlokesh N Yadav:1
[Co-author] Umashankar Sharma:1, Surender Singh:1, Yogendra K Gupta:1
1:Department of Pharmacology, All India Institute of Medical sciences, New Delhi, India

Background: Cisplatin is commonly used for different types of cancer, however nephrotoxicity is major limitation. Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation and resultant oxidative stress. Tribulus terrestris (TT), Boerhaavia diffusa (BD) and Terminalia chebula (TC) are known to possess anti-inflammatory and antioxidant activity. However the nephroprotective effect of combination of these drugs has not been elucidated. Present study has been designed to investigate the potential effects of the hydroalcoholic extract of TT alone and in combination with BD and TC in cisplatin-induced nephrotoxicity in Wistar rats.
Methods: Pretreatment of TT alone was started at a dose of 100/200/300 mg/kg p.o. once daily from day 1 to day 10 and in combination with BD, and TC (1:1:1 ratio) at a dose of (66/100/200 of each) mg/kg p.o. once daily for 10 days (n=6). Nephrotoxicity was induced by administration of a single dose of cisplatin (8 mg/kg, i.p.) on seventh day. Blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) were measured. Renal histopathology, kidney injury molecule -1 (KIM-1), liver fatty acid binding protein (L-FAB), and platinum accumulation in kidney tissue were also determined by ICPMS.
Results: Single dose of cisplatin caused significant elevation of BUN, serum creatinine, MDA, KIM-1, L-FAB and kidney platinum level and fall in GSH, SOD, GPx and histopathological changes in disease control as compared to normal control group (P <0.05). Treatment with TT 200 and 300 mg/kg alone and in combination with BD and TC (100 and 200 of each) mg/ kg significantly (P <0.05) prevented abnormalities caused by cisplatin in above parameters. The lower dose of TT 100 mg/kg alone or combination with BD and TC at 66 mg/kg of each drug did not show a significant preventation as compared to disease control group. In all drug treated groups, platinum accumulation in kidney tissues was not significantly different as control group.
Conclusions: TT alone and in combination with BD and TC exerted significant protection against nephrotoxicity induced by cisplatin and hence these herbal drugs could be beneficial in the preventation of cisplatin-induced nephrotoxicity.

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