Silymarin mitigates bile duct obstruction-induced cholemic nephropathy.

Affiliation

Ommati MM(#)(1), Farshad O(#)(2)(3), Azarpira N(4), Ghazanfari E(3), Niknahad H(5)(6), Heidari R(7).
Author information:
(1)College of Life Sciences, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.
(2)Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
(3)Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 158371345, Roknabad, Karafarin St., Shiraz, Fars, Iran.
(4)Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
(5)Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. [Email]
(6)Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 158371345, Roknabad, Karafarin St., Shiraz, Fars, Iran. [Email]
(7)Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. [Email]
(#)Contributed equally

Abstract

Bile duct obstruction or cholestasis can occur by several diseases or xenobiotics. Cholestasis and the accumulation of the bile constituents in the liver primarily damage this organ. On the other hand, extrahepatic organs are also affected by cholestasis. The kidney is the most affected tissue during cholestatic liver injury. Cholestasis-associated renal injury is known as cholemic nephropathy (CN). Several lines of evidence specify the involvement of oxidative stress and mitochondrial impairment in the pathogenesis of CN. The current study aimed to assess the role of silymarin as a potent antioxidant on CN-induced oxidative stress and mitochondrial dysfunction in the kidney. Bile duct ligated (BDL) rats were treated with silymarin (10 and 100 mg/kg, oral) for seven consecutive days. A significant increase in reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and oxidized glutathione (GSSG) levels were evident in the kidney of BDL animals. Moreover, reduced glutathione (GSH) content and total antioxidant capacity were significantly decreased in the kidney of cholestatic rats. Mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and depleted ATP stores were detected in the kidney mitochondria isolated from BDL animals. Kidney histopathological alterations, as well as serum and urine levels of renal injury biomarkers, were also significantly different in the BDL group. It was found that silymarin treatment significantly ameliorated CN-induced renal injury. The antioxidant effects of silymarin and its positive impact on mitochondrial indices seem to play a significant role in its renoprotective effects during cholestasis.