Curcumin Attenuates Oxidative Stress and Inflammatory Response in the Early Phase after Partial Hepatectomy with Simultaneous Intraabdominal Infection in Rats

Background

Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections.

Material and Methods

Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-α, IL-6 mRNA, and quantification of IL-1ß by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state.

Results

After simultaneous PH+CLP curcumin significantly reduced the expression of TNF- α and IL-6 mRNA in the liver tissue. The IL-1β concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14 ± 3%) than in the untreated PH+CLP group (7% ± 3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group.

Conclusion

In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Key Words: curcumin, partial hepatectomy, bacterial infections, CLP, glutathione, cytokines, oxidative stress