The effects of diabetes and/or polymicrobial sepsis on the status of antioxidant enzymes and pro-inflammatory cytokines on heart, liver, and lung of ovariectomized rats.

BACKGROUND

The rat sepsis model in the present study was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or together, on the response of pro-inflammatory mediators and oxidative response.

MATERIALS AND METHODS

Polymicrobial sepsis was induced using cecal ligation and two-hole puncture. Diabetes was induced in the female Wistar albino rats using intraperitoneal administration of aqueous alloxan monohydrate at a single dose of 150 mg/kg body weight. The rats were divided into five groups: sham control: group 1, ovariectomy: group 2, ovariectomy + sepsis: group 3, ovariectomy + diabetes: group 4, and ovariectomy + diabetes + sepsis: group 5.

RESULTS

In lung, heart, and liver tissues, the levels of myeloperoxidase (MPO) and lipid peroxidation (LPO) were higher for the groups 3, 4, and 5 than in control group. In heart and liver tissues, superoxide dismutase (SOD) and catalase (CAT) activities were higher for the groups 3, 4, and 5 than control group. In lung tissue SOD activities were higher for the groups 3, 4, and 5 than in control group. Diabetes + ovariectomy caused a significant increase in serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in comparison to the sham group. The strongest production of TNF-α and IL-6 in serum was observed in the group 5.

CONCLUSIONS

Hyperglycemia and ovariectomy (postmenopausal period) severely increased serum cytokines and oxidant levels with the stages of our sepsis model. The lung tissue was most affected by diabetes and ovariectomy under sepsis conditions. Ovariectomy leading to estrogen deficiency results in general changes in metabolism, which are seen in the liver, lungs, and heart with diabetes under sepsis conditions.