The effect of progesterone on systemic inflammation and oxidative stress in the rat model of sepsis

OBJECTIVES: To explore the protective effect of progesterone on inflammation and oxidative stress in a rat model of sepsis created by cecal ligation and puncture (CLP). MATERIALS AND METHODS: Rats were randomly divided into 4 groups: Overiectomy group (OVX), sham operated (control), sepsis (CLP) group and progesterone-treated CLP group (CLP+ progesterone). The rats in CLP+ progesterone group received intraperitoneal progesterone (2 mg/kg). Cardiac blood samples were obtained for the measurement levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Tissue samples, including liver, kidney and uterus of rats were prepared to determine activities of myeloperoxidase (MPO), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). RESULTS: Increased serum IL-6 and TNF-α levels were found in the CLP group in comparison with the control group (P = 0.01, P = 0.02; respectively). In CLP+ progesterone group, mean MDA concentration of kidney tissue was significantly lower than in CLP group (P = 0.003). Liver MDA concentration of the CLP+ progesterone group was not significantly different from that of the control group. While there were no significant differences among groups regarding liver MPO; in the CLP group, MPO activity in kidney (P = 0.02) and uterine tissues (P = 0.03) were found to be significantly higher compared to the control group. In CLP+ progesterone group, mean MPO activities of all tissues were not different than those of control group. The uterine tissue GPx activity in the CLP+ progesterone group was not statistically significantly different from control group. CONCLUSIONS: We suggest that progesterone ameliorates sepsis syndrome by reduction of the inflammatory cytokines IL-6 and TNF-α, and by restoration of antioxidant enzyme activities in some tissues.