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Published on: April 11, 2012
Hepatic effects of flunixin-meglumin in LPS-induced sepsis
Thiago Vinicius Avila1, Amanda Leite Bastos Pereira, Adriana De Oliveira Christoff
1Department of Pharmacology, Federal University of Paraná, Curitiba, Paraná, Brazil.
Abstract:
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.
Insights
Flunixin-meglumine (FM) protects the rat liver from sepsis-induced damage by reducing inflammation and oxidative stress. This non-steroidal anti-inflammatory drug treatment helps maintain liver function and structure during sepsis.
Area of Science:
- Pharmacology
- Hepatology
- Toxicology
Background:
- Sepsis, induced by lipopolysaccharide (LPS), causes significant liver damage.
- LPS-induced sepsis leads to oxidative stress, inflammation, and impaired liver metabolic functions.
Purpose of the Study:
- To evaluate the protective effects of flunixin-meglumine (FM) against LPS-induced liver injury in rats.
- To assess FM's impact on liver enzymes, histology, antioxidant status, and metabolic fluxes during sepsis.
Main Methods:
- Adult male Wistar rats were divided into control, FM-treated, LPS-injected, and LPS-injected with FM (pre- and post-treatment) groups.
- Evaluated plasma hepatic enzymes, urea, liver histology, antioxidant enzymes (catalase, superoxide dismutase), and metabolic fluxes (gluconeogenesis, ureagenesis, oxygen consumption).
Main Results:
- LPS-induced sepsis caused liver damage, elevated liver enzymes (ALT, AST), impaired gluconeogenesis and ureagenesis, and increased oxidative stress (lipid peroxidation, antioxidant enzyme activity).
- FM pretreatment significantly minimized histological damage and normalized enzyme activities.
- FM pretreatment also normalized gluconeogenesis and partially restored ureagenesis, suggesting antioxidant and anti-inflammatory protective mechanisms.
Conclusions:
- LPS-induced sepsis severely damages rat liver structure and function.
- Flunixin-meglumine demonstrates protective effects against LPS-induced liver injury, partly due to its antioxidant properties.
- FM treatment is a potential therapeutic strategy to mitigate sepsis-related liver damage.
