Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E2) loss and E2 supplementation on the progress of CRF were studied. Sprague-Dawley rats underwent 5/6 nephrectomy (CRF), and a group of female rats had bilateral ovariectomy (OVX), while the sham-operated rats had no nephrectomy or OVX. Rats received either estradiol propionate (50 μg/kg/day) or vehicle for six weeks. Serum BUN levels were elevated in both male and female CRF groups treated with vehicle, while creatinine level was not significantly changed in the female CRF group. CRF-induced elevation in serum TNF-α of male rats was abolished when the animals were treated with E2, while OVX exaggerated TNF-α response. In OVX and male rats with CRF, E2 treatment reversed the malondialdehyde elevations in all the studied tissues (kidney, heart, lung, ileum, brain, liver, and gastrocnemius muscle), while depletion of glutathione in these tissues was prevented by E2 treatment. Similarly, increased levels of myeloperoxidase activity, lucigenin chemiluminescence, and collagen in most of the tissues were reversed by E2 treatment. The findings show that the extent of tissue injuries was relatively less in females, while ovariectomy exacerbated all the indices of oxidative injury. Moreover, the administration of E2, with its potent anti-oxidant and anti-inflammatory effects, markedly improved CRF-induced systemic inflammatory outcomes in both male and female rats by depressing tissue neutrophil infiltration and modulating the release of inflammatory cytokines.