Hepatic effects of flunixin-meglumin in LPS-induced sepsis

The aim of this study was to evaluate the actions of the non-steroidal anti-inflammatory drug flunixin-meglumin (FM) on the changes caused by lipopolysaccharide (LPS)-induced sepsis in the rat liver. Eight groups of five adult male Wistar rats were analysed: (1) saline injected (controls), (2) FM treated with 1.1 mg/kg, (3) FM treated with 2.2 mg/kg, (4) LPS-injected (10 mg/kg), (5) LPS-injected with 1.1 mg/kg FM pretreatment, (6) LPS-injected with 2.2 mg/kg FM pretreatment, (7) LPS-injected with 1.1 mg/kg FM post-treatment and (8) LPS-injected with 2.2 mg/kg FM post-treatment. All drugs were intraperitoneally injected. The following parameters were evaluated: plasma levels of hepatic enzymes and urea, hepatic histological characteristics, antioxidant enzymes and several metabolic fluxes. The latter comprised gluconeogenesis, ureagenesis and oxygen consumption. Liver damage in LPS-induced sepsis was characterized by histological changes, increased plasma levels of alanine aminotransferase and aspartate aminotransferase (P < 0.001) and diminished gluconeogenesis (P < 0.001) and ureagenesis (P < 0.01). LPS also induced oxidative stress as evidenced by increased catalase (P < 0.05) and superoxide dismutase activities and enhanced lipid peroxidation (P < 0.001). Pretreatment of the animals with FM minimized the histological changes and normalized, in part, all enzymatic activities. Pretreatment of the animals with FM also normalized gluconeogenesis and partly restored ureagenesis (P < 0.05). These and other results show that LPS-induced sepsis may lead to severe liver damage, affecting both structure and function. Treatment with FM can be used to avoid this damage. The antioxidant properties of FM can be, partly at least, responsible for this protective action.