title: 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.
authors.affiliation: Department of Toxicology, Center for Disease Control and Prevention of Guangdong Province, Hai Zhu District, Guangzhou, China. luiassay@sina.cn
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Lv
authors.forename: Baoxu
authors.initials: B
authors.lastname: Zhang
authors.forename: Guozhen
authors.initials: G
authors.lastname: Xing
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wang
authors.forename: Zhewen
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D044950:Flavanones / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020011:Protective Agents / Q000008:administration & dosage*
chemical_list: D044950:Flavanones; D020011:Protective Agents; D000082:Acetaminophen; D008315:Malondialdehyde; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C005273:naringenin