Protective effect of aminoguanidine against lipopolysaccharide-induced hepatotoxicity and liver dysfunction in rat.

Lipopolysaccharide (LPS) as the major component of the outer membrane of Gram-negative bacteria activates macrophages to produce a high level of pro-inflammatory cytokines which is considered as a cause of liver dysfunction. Overproduction of nitric oxide (NO) has been suggested to have a role in hepatic injury. The aim of the present study was to explore the protective effects of aminoguanidine (AG) as inducible nitric oxide synthase (iNOS) inhibitor against LPS -induced liver dysfunction in rat. The animals were divided into five groups: (1) control (2) LPS (3) LPS-AG50, (4) LPS-AG100 and (5) LPS-AG150. LPS (1 mg/kg) was injected for 5 weeks and AG (50, 100 and 150 mg/kg) was administered 30 min before LPS. Drugs were injected intraperitoneally. LPS induced liver dysfunction presented by increasing the serum level of alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Pretreatment with AG restored harmful effects of LPS on liver function. In addition, LPS resulted in hepatotoxicity, accompanied by enhancing the level of interleukin (IL)-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreasing the content of total thiol groups and superoxide dismutase (SOD) and catalase (CAT) activity. Injection of AG before LPS attenuated LPS-induced hepatotoxicity through decreasing the level of IL-6, MDA and NO metabolites and increasing total thiols and SOD and CAT activity. Considering the protective effect of AG which was seen in the present study, it seems that increased levels of NO due to activation of iNOS has a role in LPS-induced hepatic injury.