A Study of Hepatoprotective Mechanism of Estrogen in Lipopolysaccharide Induced Liver Sepsis in Male and Female Albino Rats

Sepsis is distinguished by a systemic inflammatory response and multi-organ dysfunction, affecting the lungs, heart, kidneys, and liver. To evaluate the hepatoprotective effect of estrogen and compare hepatic responses among male, female, ovariectomized, and estrogen-treated ovariectomized rats following LPS-induced sepsis. Sixty Wistar albino rats (20 males and 40 females) were randomly assigned into six groups: male and female control groups, male and female sepsis groups, female ovariectomy-sepsis group, and female ovariectomy-estrogen-sepsis group. Sepsis was induced via a single intraperitoneal injection of LPS at a dose of (5 mg/kg of body weight), while 17ẞ-estradiol was administered to evaluate its protective effects i.p. at a dose of 5 mg/kg /day for a week following ovariectomy operation. LPS-induced sepsis significantly increased serum AST, ALT, ALP, IL-1β, IL-10, and MDA levels while decreasing total antioxidant capacity (TAC). Female rats exhibited lower liver enzyme, inflammatory and oxidative marker elevations and higher TAC compared to males, indicating a protective role of endogenous estrogen. Administration of 17ẞ-estradiol to ovariectomized female rats significantly mitigated LPS-induced liver injury, reflected by reduced liver enzyme levels, inflammatory cytokines, and oxidative stress. Both endogenous and exogenous estrogen provide significant hepatoprotection against lipopolysaccharide-induced liver sepsis. Estrogen deficiency, as in ovariectomized and postmenopausal females, may increase susceptibility to sepsis. These findings support further investigation of estrogen as a potential adjunctive therapeutic strategy for sepsis-associated liver injury.