Protective effect of pioglitazone on ovarian ischemia reperfusion injury of female rats via modulation of peroxisome proliferator activated receptor gamma and heme-oxygenase 1

Abstract

Ovarian torsion is a dangerous gynecological emergency condition. Early diagnosis of this case is necessary to preserve the function of the ovaries and fallopian tubes and prevent further damage. Ovarian torsion means complete or partial rotation of the adnexa with ischemia followed by reperfusion period. Ovarian torsion affects 2%–15% of patients who have surgical treatment of adnexal masses. We investigated the effect of pioglitazone (PIO) on induced ovarian ischemia reperfusion (OIR). PIO (10, 30 mg/kg) was administered orally in the presence or absence of induced OIR. We measured ovarian tissue malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), heme-oxygenase 1 (HO-1), and gene expressions of peroxisome proliferator activated receptor gamma (PPARγ), tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Moreover, expression of p53 and histopathological changes were also evaluated. Results showed increase in the ovarian tissue levels of MDA and NOx and gene expressions of p53, TNFα, and iNOS in the induced OIR group. The induced OIR group showed the histopathological changes associated with cell injury, marked ovarian edema, hemorrhage and congestion. In addition, there was reduction in the GSH, HO-1 levels and PPARγ, eNOS gene expressions. PIO was able to reduce these induced OIR changes to levels insignificant from control group. This protective effect of PIO may be attributed to its PPARγ agonist effect, anti-inflammatory, anti-apoptotic and anti-oxidant properties.