| Objective:Perfluorooctanoic acid(PFOA),a member of the typical perfluorinated compounds,is widely used in the manufacture of food packaging,electronic products,cosmetics and other industries.Because of its high stability,PFOA is ubiquitous and nonbiodegradable in the environment and bioaccumulates in the food chain.Food intake,water and airborne are the mian sources of PFOA.It has been shown that PFOA elicits a variety of toxicities in various tissues and organs.Epidemiologic studies have also demonstrated that PFOA exposure is associated with cardiovascular disease,chronic kidney disease and thyroid disease.The liver serves as the main target organ for PFOA,which can cause liver injury.Morin(Mor),a kind of flavonoid extracted from the genus,has a variety of pharmacological effects such as anti-oxidative,anti-cancer and anti-inflammatory actions.The present study was designed to investigate the protective effect of Mor on PFOA-induced liver injury and the possible hepatoprotective mechanisms of Mor in mice.Methods:Experiment 1: After 1 week of acclimatization,32 male mice were randomly divided into four groups: control group,low PFOA exposure group(2.5 mg/kg/day),medium PFOA exposure group(5 mg/kg/day)and(10 mg/kg/day),with 8 mice in each group.After treatment for 14 consecutive days,liver histopathology,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)activities and hepatic malondialdehyde(MDA),H2O2,C-reactive protein(CRP),interleukin-6(IL-6)and cyclooxygenase-2(COX-2)levels were measured in all groups.Experiment 2: After 1 week of acclimatization,32 male mice were randomly divided into four groups: control group,PFOA group(10 mg/kg/day),Mor group(75mg/kg/day)and PFOA+Mor group(PFOA 10 mg/kg/day and Mor 75 mg/kg/day),with 8 mice in each group.After treatment for 14 consecutive days,liver histopathology,serum ALT,AST and ALP activities and hepatic MDA,superoxidedismutase(SOD),catalase(CAT),IL-6 and COX-2 levels were measured in all groups.Results:Experiment 1:(1)Effect of PFOA on liver histopathology in mice: Histological examination of liver sections showed deranged liver architecture,severe edema,vacuolar degeneration,focal necrosis,and obvious infiltration of inflammatory cells in mice exposed to PFOA.The maximal effect was found at the highest concentration(10mg/kg/day).(2)Effect of PFOA on serum enzyme levels in mice: PFOA exposure induced an obvious increase in serum ALT levels in a dose-dependent manner(P<0.05).Compared with the control group,serum AST and ALP levels were obviously increased by PFOA administration(5-10 mg/kg/day)(P<0.05).There was no significant reduction in serum AST and ALP levels in the lowest exposure group(2.5mg/kg/day)compared with the control group(P>0.05).(3)Effect of PFOA on hepatic oxidative stress in mice: After exposure to PFOA for 14 days,the levels of MDA and H2O2 in the liver tissue significantly increased compared with the control group(P<0.05).The lowest dose of PFOA had no effect on H2O2 generation compared with the control group(P>0.05).(4)Effect of PFOA on hepatic inflammatory response in mice: The high concentration of PFOA(10 mg/kg/day)significantly increased hepatic CRP,IL-6 and COX-2 levels compared with the control group(P<0.05).The low-dose exposure to PFOA(2.5 mg/kg/day)did not altered the hepatic levels of the three cytokines(P>0.05)Experiment 2:(1)Effect of Mor on liver histopathology in PFOA-treated mice: Mor intervention obviously ameliorated the histopathological changes induced by PFOA.Hepatocyte necrosis and inflammatory cell infiltration were significantly reduced by treatment with Mor.(2)Effect of Mor on serum enzyme levels in PFOA-treated mice: Compared with control group,oral administration of PFOA resulted in a significant increase inserum ALT,AST and ALP levels.However,simultaneous supplementation of Mor markedly decreased the levels of these biochemical markers of liver function in PFOA-treated mice(P<0.05).(3)Effect of Mor on hepatic oxidative stress in PFOA-treated mice:Compared with control group,lipid peroxidation product MDA formation increased and antioxidant enzymes SOD and CAT activities decreased in PFOA group(P<0.05).However,mice in PFOA+Que group showed a decrease in MDA formation and an increase in activities of SOD and CAT,compared with PFOA group(P <0.05).(4)Effect of Mor on hepatic inflammatory response in PFOA-treated mice:Compared with control group,hepatic inflammatory response markers CRP,IL-6 and COX-2 levels significantly increased in PFOA group(P<0.05).However,mice in PFOA+Que group showed a obvious decrease in hepatic levels of these markers,compared with PFOA group(P<0.05).Conclusions:Exposure to PFOA can induce hepatotoxicity involving oxidative stress and inflammatory response in mice.Mor protects against PFOA-induced liver damage through attenuating oxidative stress and reducing the production of inflammatory cytokines. |
