The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats

Area of Science:

• Renal pathophysiology
• Endocrinology
• Inflammation research

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Hyperglycemia and ovariectomy are common conditions that can influence inflammatory and oxidative stress pathways.
• The combined effects of hyperglycemia and ovariectomy on sepsis-induced kidney injury are not fully understood.

Purpose of the Study:

• To investigate the impact of sustained hyperglycemia and ovariectomy on nuclear factor kappa B (NF-kappaB) activation and oxidative stress in a sepsis model.
• To determine the individual and combined effects of these conditions on kidney injury.

Main Methods:

• A polymicrobial sepsis model was induced using cecal ligation and puncture (CLP) in female rats.
• Diabetes was induced using alloxan, and ovariectomy was performed.
• Rats were divided into five groups: control, ovariectomy, ovariectomy + sepsis, ovariectomy + diabetes, and ovariectomy + diabetic + sepsis.

Main Results:

• Sepsis, ovariectomy, and diabetes individually increased kidney oxidative stress markers (lipid peroxidation, glutathione, catalase) and decreased superoxide dismutase activity.
• Sepsis induced significant kidney injury, which was exacerbated by the combination of diabetes and ovariectomy.
• NF-kappaB activation was significantly elevated in the ovariectomized, septic, and diabetic group compared to other groups.

Conclusions:

• Sustained hyperglycemia and ovariectomy severely enhance NF-kappaB activation and oxidant levels in a sepsis model.
• Ovariectomy induces metabolic alterations in the kidney that are compounded by diabetes under sepsis conditions.
• These findings highlight the critical role of hyperglycemia and ovariectomy in modulating the host response to sepsis and kidney injury.