Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage

Abstract

-Recent studies have shown that dehydroepiandrosterone (DHEA) administration after trauma-hemorrhage (T-H) improves cardiovascular function and decreases cytokine production in male animals. Although androstenediol, one of the metabolites of DHEA, is reported to have estrogen-like activity, it remains unknown whether androstenediol per se has any salutary effects on cytokines and cardiovascular function after T-H. To examine this effect, male Sprague-Dawley rats underwent laparotomy and were bled to and maintained at a mean arterial blood pressure of 35-40 mmHg for ϳ90 min. The animals were resuscitated with four times the volume of maximal bleedout volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) or vehicle was administered at the end of resuscitation. Twenty-four hours after resuscitation, cardiac function and organ blood flow were measured by using 85 Sr-microspheres. Circulating levels of nitrate/nitrite and IL-6 were also determined. Cardiovascular function and organ blood flow were significantly depressed after T-H. However, these parameters were restored by androstenediol treatment. The elevated plasma IL-6 levels after T-H were also lowered by androstenediol treatment. In contrast, plasma levels of nitrate/nitrite were the highest in the androstenedioltreated T-H animals. Because androstenediol administration after T-H decreases cytokine production and improves cardiovascular function, this agent appears to be a novel and useful adjunct for restoring the depressed cardiovascular function and for cytokine production in males after adverse circulatory conditions. hemorrhagic shock; nitric oxide; nitric oxide synthase; adiol; 5-androstene-3␤,17␤-diol HEMORRHAGIC SHOCK results in a rapid decrease in cardiac output and organ blood flow. Furthermore, studies have shown that intestinal perfusion remains depressed even after the recovery of cardiac output by fluid resuscitation (29). This splanchnic hypoperfusion after hemorrhagic shock also activates the inflammatory cascade. The depressed cardiovascular function and excess production of inflammatory mediators play an important role in the development of multiple organ failure after hemorrhagic shock (20).Previous work from our laboratory has shown that left ventricular performance, cardiac output, and organ blood flow in the liver, small intestine, and kidney decreased significantly after trauma-hemorrhage (3,4,25), and plasma levels of IL-6

Effects of α/β-androstenediol immune regulating hormones on bone remodeling and apoptosis in osteoblasts

“…These results indicate directly opposite effects on PPAR-␥ activation in osteoblast cells by treatment of ␣-AED versus ␤-AED that explain a mechanism of action by androstenediol compounds in bone cells. As previously reported, ␤-AED was shown to increase activation of PPAR-␥ in heart tissue [41], indicating the regulation of PPAR-␥ by ␤-AED is tissue-specific.…”

The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage

“…All experiments were performed in adherence to National Institutes of Guide for the Care and Use of Laboratory Animals and approved by the University of Alabama at Birmingham Institutional Animal Care and Use Committee. After fasted overnight, rats were anesthetized by isoflurane (Attane, Minrad Inc., Bethlehem, PA) inhalation prior to induction of soft tissue trauma via 5-cm midline laparotomy [28]. The abdomen was closed in layers, and catheters were placed in both femoral arteries and right femoral vein (polyethylene tubing; Becton Dickinson & Co., Sparks, MD).…”

Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway

“…AED has been reported to have protective effects against ionizing radiation-induced injury in mice (28,55), lethal bacterial infections, and endotoxic shock (35). AED has also been shown to preserve cardiovascular function (42) and hepatic function (44) after trauma plus hemorrhage (T-H), to reduce injury from behavioral stress (14), to promote wound repair (14), and to attenuate inflammation caused by viral infection (5). AED treatment also inhibits hemorrhage-induced decreases in portal blood flow, bile production, and serum albumin levels, and increases portal pressure, hepatic nitrate/nitrite, iNOS, and endothelin-1 levels (43).…”