The hepatoprotective role of reduced glutathione and its underlying mechanism in oxaliplatin-induced acute liver injury.

The hepatoprotective role of reduced glutathione and its underlying mechanism in oxaliplatin-induced acute liver injury.

Oncol Lett. 2018 Feb;15(2):2266-2272

Authors: Lin Y, Li Y, Hu X, Liu Z, Chen J, Lu Y, Liu J, Liao S, Zhang Y, Liang R, Lin Y, Li Q, Liang C, Yuan C, Liao X

Abstract
Currently, the underlying mechanism of oxaliplatin (OXA) induced live injury is unclear. In addition, there is no standard clinical treatment for OXA-induced acute liver injury (ALI). In this study, we established an animal model of OXA-induced ALI, and studied the role of oxidative stress in OXA-induced ALI and the impacts of reduced glutathione (GSH) treatment on OXA-induced ALI. To establish an OXA-induced ALI model, KM mice received intraperitoneal injection of OXA (8 mg/kg) for 4 days. Serum alanine aminotransferase (ALT), aspartate aminotransferase levels (AST), hepatic pathology and oxidative stress indicators in liver tissues were analyzed. To study the impact of GSH treatment on OXA-induced ALI, mice were treated with GSH (400 mg/kg, i.p). In this ALI mouse model, ALT and AST levels were significantly increased (P<0.01). Liver pathological examination revealed varying degrees of liver cell turbidity and degeneration, even balloon-like changes and focal necrosis, and sinusoidal hemorrhage in some cells. Compared with control group, the malondialdehyde (MDA) and GSH levels were significantly increased in OXA-treated group (P<0.01), while the superoxide dismutase SOD and GSH-peroxidase levels were decreased after OXA withdrawal (P<0.01). When GSH was used to treat OXA-induced ALI mice, the pathological injury of liver tissues was alleviated, and serum ALT and AST were significantly decreased. In addition, GSH treatment could reduce the OXA-induced increase of MDA level (P<0.05) in liver tissues, but had no impact on SOD level (P>0.05). We have successfully established an OXA-induced ALI model. Using this model, we discover that oxidative stress plays an important role in OXA-induced ALI. GSH-based hepatoprotective therapy can partially inhibit oxidative stress and alleviate OXA-induced ALI.

PMID: 29403564 [PubMed]

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