Protective effect of naringenin against acetaminophen-induced acute liver injury in metallothionein (MT)-null mice

Abstract

Naringenin is a natural flavonoid aglycone of naringin that has been reported to have a wide range of pharmacological properties, such as antioxidant activity and free radical scavenging capacity. This study was designed to examine the hepatoprotective effect of naringenin against acetaminophen (250 mg kg⁻¹, sc) in metallothionein (MT)-null mice. 42 SPF MT-knockout mice were used. Naringenin (200, 400, and 800 mg kg⁻¹, ig) was administered for 4 days before exposure to acetaminophen (250 mg kg⁻¹, sc). Liver injury was measured by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as liver malondialdehyde (MDA). The glutathione-to-oxidized glutathione ratio (GSH/GSSG) was also assessed. The evidence of liver injury induced by acetaminophen included not only a significant increase in the levels of serum ALT, AST, LDH and liver MDA, and also a significant decrease in GSH/GSSG. Pretreatment of mice with naringenin at 400 and 800 mg kg⁻¹ reversed the altered parameters. Such reversal effects were dose-dependent: ALT decreased 78.62% and 98.03%, AST decreased 88.35% and 92.64%, LDH decreased 76.54% and 81.63%, MDA decreased 48.59% and 66.27% at a dose of 400 and 800 mg kg⁻¹ respectively; GSH/GSSG increased 22.57% and 16.93% at a dose of 400 and 800 mg kg⁻¹ respectively. Histopathological observation findings were also consistent with these effects. Together, this study suggests that naringenin can potentially reverse the hepatotoxic damage of acetaminophen intoxication in MT-null mice.