Role of Estrogen in Acute Ischemic Reperfusion Renal Injury in Adult Female Rats and its Possible Underlying Mechanisms of Action

Renal ischemic reperfusion Injury (I/R) is an important clinical problem that shows sex differences thus there was a specific role of sex steroids in renal injury. This study aimed to investigate the protective effect of estrogen as an anti-inflammatory and anti-oxidant agent in renal I/R injury. Five groups were included (n=10/group): Sham-operated, I/R of the kidney, I/R after bilateral ovariectomy, I/R after bilateral ovariectomy and estrogen supplementation and I/R after bilateral ovariectomy with estrogen supplementation and L-NAME. When compared with the sham-operated group, I/R resulted in significant increase in the serum creatinine (0.46±0.17mg/dl versus 0.15±0.06mg/dl), rat tail systolic B.P. (116.9±5.09mmHg versus 110.2±2.44mmHg), p-38 MAPK (0.82±0.12 versus 0.27±0.09) and peroxynitrite level (186.08±21.9nmol/mg ptn versus 101.25±11.09nmol/mg ptn) and significant decrease in e-NOS (0.6±0.38 versus 1.98±0.58), bilateral ovariectomy with estrogen supplementation resulted in significant decrease in serum creatinine (0.5±0.17mg/dl versus 0.82±0.13mg/dl), rat tail systolic B.P. (116±3.06mmHg versus 121.4±6.35mmHg), p-38 MAPK (0.6±0.16 versus 1.30±0.34) and peroxynitrite (162.89±21.04 versus 204.24± 12.41) and significant increase in e-NOS (1.347±0.42 versus 0.22±0.08) compared to I/R after ovariectomy. In Conclusion: Estrogen provided a protective role against renal I/R injury and subsequent dysfunction as it produced an anti-oxidant impact mediated by increased expression of e-NOS and decreased peroxynitrite in renal tissue and anti-inflammatory effects manifested by decreased expression of p38 MAPK in renal tissue. L-NAME blocking the anti-oxidant effect of estrogen suggests that it may be mediated through NO action.