Neurotensin agonist PD149163 modulates lipopolysaccharide induced inflammation and oxidative stress in the female reproductive system of mice.

ABSTRACT

Inflammation-mediated reproductive health problems in females have become an emerging concern. The present investigation was aimed to elucidate the efficacy of the PD149163, agonist of the type I neurotensin receptor, in preventing/ameliorating the lipopolysaccharide (LPS) induced inflammation of the female reproductive system of the mice. Female Swiss Albino Mice (8 weeks old) were maintained in three groups (6/group) Group I as Control, Group II and Group III were exposed to intraperitoneal (i.p) LPS (1 mg/kg bw) for 5 days followed by treatment with PD149163 (100 µg/kg BW i.p.) to Group III (LPS + PD) for 28 days. After termination of the experiment on 29th day, plasma levels of inflammatory cytokines, LH, FSH, estradiol, corticosterone, oxidative stress effects in the ovary and histopathological study of the ovary and uterine horn were done. LPS-induced inflammation of the ovary and uterine horn was ameliorated/prevented by PD149163 as reflected in the reduced histopathological scores, significant elevation of the plasma anti-inflammatory cytokine IL-10 and decrease of the pro inflammatory cytokines TNF-α and IL-6. Significant decrease of lipid peroxide, increase of antioxidant defense enzymes, Superoxide dismutase and Catalase in the ovary indicated reduction of oxidative stress. The plasma levels of the reproduction related hormones and corticosterone were restored. PD149163 acts as an anti-inflammatory and anti-oxidative agent in modulation of inflammation in the female reproductive system (ovary & uterine horn). These findings suggest that the therapeutic potential of the analogs of neurotensin including PD149163 should be explored for the treatment of the female reproductive health issues.