Male susceptibility to hepatic damage in acute uremia in rats

To evaluate the role of gender in hepatic oxidative stress response and production of inflammatory cytokines in acute uremia after bilateral nephrectomy. Published studies indicate that the severity of tissue damage in kidney, brain, or heart injury may differ according to gender. We recently demonstrated that acute renal failure after kidney injury or bilateral nephrectomy activates oxidative stress and causes damage to the liver.

Male and female rats were subjected to bilateral nephrectomy and euthanized four hours later. Serum and liver tissues were collected and analyzed. To ascertain the role of testosterone and estrogen in hepatic oxidative stress, castration was carried out 15 days before bilateral nephrectomy. In some groups, animals were administrated 17-β-estradiol or vehicle for 2 weeks before bilateral nephrectomy.

Hepatic oxidative stress was significantly pronounced in male rats as determined by increase in malondialdehyde (MDA) levels and decrease in total glutathione (GSH) contents. An increase in proinflammatory cytokine concentration was seen in male rats, whereas the antiinflammatory cytokine level was more elevated in females. Castration reduced hepatic oxidative stress and proinflammatory cytokine concentration, whereas exogenous estradiol after castration did not have an additional effect on these parameters.

There is a gender difference with regard to the severity of hepatic oxidative stress and inflammatory response in acute uremia after bilateral nephrectomy, with female rats displaying significant protection relative to male rats. We suggest that sex hormones could play an important role in the severity of remote tissue damage in acute kidney failure.