Dehydroepiandrosterone-dependent induction of peroxisomal proliferation can be reduced by aspartyl esterification without attenuation of inhibitory bone loss in ovariectomy animal model.

The purpose of this study was to determine whether esterification of dehydroepiandrosterone with aspartate (DHEA-aspartate) could reduce peroxisomal proliferation induced by DHEA itself, without loss of antiosteoporotic activity. Female Sprague-Dawley rats were ovariectomized, then DHEA or DHEA-aspartate was administered intraperitoneally at 0.34 mmol/kg BW 3 times a week for 8 weeks. DHEA-aspartate treatment in ovariectomized rats significantly increased trabeculae area in tibia as much as DHEA treatment. Urinary Ca excretion was not significantly increased by DHEA or DHEA-aspartate treatment in ovariectomized rats, while it was significantly increased by ovariectomy. Osteocalcin concentration and alkaline phosphatase activity in serum and cross linked N-telopeptide type I collagen level in urine were not significantly different between DHEA-aspartate and DHEA treated groups. DHEA-aspartate treatment significantly reduced liver weight and hepatic palmitoyl-coA oxidase activity compared to DHEA treatment. DHEA-aspartate treatment maintained a nearly normal morphology of peroxisomes, while DHEA treatment increased the number and size of peroxisomes in the liver. According to these results, it is concluded that DHEA-aspartate ester has an inhibitory effect on bone loss in ovariectomized rats with a marked reduction of hepatomegaly and peroxisomal proliferation compared to DHEA.

Can antioxidant supplementation slow the aging process?

The oxidative stress theory of aging is well supported by accumulated evidence from various aging intervention studies. Early antioxidant supplementation studies indicate life span extensions by antioxidant feeding in various experimental organisms. Data collected under tightly controlled conditions show that the feeding of 2-mercaptoethanol (0.25%) effectively prolonged both the median and maximum life spans of mice. Evidence has been obtained showing dietary vitamin E to protect against oxidative damage to DNA in human lymphocytes and white blood cells. Other clear evidence of vitamin E's protective effect has been seen in its suppressive action of LDL oxidation both in vitro and in vivo. New evidence on the physiological roles of antioxidants, in addition to their well-known role as free radical scavengers, is emerging from recent research. For instance, the beneficial effect of vitamin E in improving glucose transport and the insulin sensitivity and its putative role as a regulator of cell proliferation should open new research dimensions. This presentation will review some of the anti-aging aspects of dietary antioxidant supplementation, as well as the potential problems of its long-term administration that stem from our lack of knowledge about free radical metabolism and the regulation of endogenous defense mechanisms.