Volume 16, Issue 38, July - December, 2022

Hepatoprotective effects of gabapentin alone or with silymarin in carbon tetrachloride-induced hepatic damage in rats

Omar M E Abdel-Salam^1♦, Nermeen Shafee², Amany A Sleem³

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt
²Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

^♦Corresponding author
Department of Toxicology and Narcotics, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt

ABSTRACT

The aim of this study was to examine the effect of gabapentinoid drug gabapentin alone or in combination with the antioxidant silymarin on the carbon tetrachloride (CCl4)-induced liver injury in rats. Gabapentin at doses of 25, 50, or 100 mg/kg, silymarin at 25 mg/kg, or gabapentin combined with silymarin was given once orally a day at the time of CCl4 administration and for 2 weeks thereafter. Liver damage was assessed by determination of serum activities of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in addition to hepatic histopathology. Gabapentin given at the above doses showed significant protective effect against the hepatotoxicity caused by of CCl4 rats, reducing serum ALT activities by 24.7%, 40.8% and 57.8%, respectively, compared to CCl4 control group. Serum AST activities decreased by 26.5%, 41.4% and 66.1%, while ALP activities decreased by 27.7%, 38% and 58.9%, respectively. Silymarin given alone resulted in significant decrease in ALT, AST and ALP activities by 59.3%, 62.1% and 54.6%, respectively. Significant differences in ALT were observed between silymarin/gabapentin vs. their respective gabapentin (50 mg/kg) only group. Moreover, there were significant differences in AST between silymarin/gabapentin (25 and 50 mg/kg) compared with their respective gabapentin only groups. The histopathological alterations caused by CCl4 were dose-dependently reduced after treatment with gabapentin alone or in combination with silymarin. These results indicate that that treatment with gabapentin protects against acute liver injury due to CCl4. The study suggests a potential benefit for silymarin/gabapentin combination in treatment of liver injury.

Keywords: gabapentin, silymarin, carbon tetrachloride, liver disease

Drug Discovery, 2022, 16(38), 124-130

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