Dehydroepiandrosterone restores hepatocellular function and prevents liverdamage in estrogen-deficient females following trauma and hemorrhage

Introduction. Recent studies have shown that administration of the sex ster oid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic sho ck has salutary effects on the depressed cardiovascular and immunological f unctions under those conditions. Since the effects of sex steroids are gend er specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Methods. Ovariectomy was performed in female Sprague-Dawley rats 14 days pr ior to the experiments. The animals then underwent a 5-cm midline laparotom y and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was f ollowed by fluid resuscitation (Ringer's lactate over 60 min) and administr ation of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resusci tation. At 24 h after resuscitation hepatocellular function, i.e., clearanc e of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotra nsferase) were measured. Plasma levels of DHEA and 17 beta -estradiol were also assayed. Results. Vehicle-treated rats had significantly reduced hepatocellular func tion, increased ALT activity, and decreased levels of 17 beta -estradiol fo llowing trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOV A and Student-Newman-Keuls test). In animals receiving DHEA following traum a-hemorrhage, hepatocellular function and ALT activity were similar to thos e of shams. However, administration of DHEA did not influence the plasma le vels of 17<beta>-estradiol, Conclusions. Administration of DHEA following trauma-hemorrhage restored he patocellular function and reduced hepatic damage that was observed in ovari ectomized female rats under such conditions. This salutary effect of DHEA d id not appear to be due to elevated levels of plasma 17 beta -estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in o variectomized and postmenopausal females. (C) 2001 Academic Press.