Therapeutic Effects of Hesperetin and Nano Hesperetin on Ketamine-Induced Hepatotoxicity

Abstract

Background: Ketamine (KET) causes oxidative stress and liver damage. Hesperetin plays an important role in the prevention of inflammatory processes and associated with oxidative stress. Objective: The purpose of this study was to analyze the protective role of hesperetin and its nanocrystal on hepatotoxicity induced by ketamine in mice. Methods: In this research, 30 male mice were divided into six groups: control, poisoned (KET 10 mg/kg/10 day injected intraparitary), hesperetin and hesperetin nanoparticles treated poisoning groups (10 and 20 mg/kg for four weeks orally after KET administration). Finally, the malondialdehyde (MDA) and glutathione (GSH) levels, Catalase (CAT), Superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Glutathione reductase (GRX) activity in liver tissue as well as the its histological changes were investigated. Results: The level of GSH and antioxidant enzyme activity in the liver were significantly (P <0.05) decreased in the ketamin indused rat, and hesperetin and its nano significantly were increased (P <0.01) GSH level and antioxidant enzyme activity. In contrast, MDA level in the liver was significantly (P <0.01) increased in the the ketamin poioned rat, and nano hesperetin suppressed the ketamin-induced lipid proxidation. Ketamine also decreased number of hepatocytes (P<0.001) and diameter of sinusoids (P <0.05) in toxic mice. Whereas, Nano hesperetin increased antioxidant enzymes activities, diameter and nucleus diameter of hepatocytes and decreased MDA level (P <0.05). Conclusion: The results of this study indicated that hesperetin and especially nano hesperetin due to antioxidant effects cause hepatoprotective against KET-induced oxidative stress.

Keywords

• antioxidant enzymes
• hesperetin
• liver damage
• nano hesperetin
• ketamine