Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage

Abstract

Osteoarthritis (OA) is aggravated in menopausal women possibly because of changed serum estrogen levels. Estradiol has been postulated to affect oxidative stress induced by reactive oxygen species (ROS) in articular chondrocytes. We generated ROS in cultured bovine articular chondrocytes by incubating them with combined Fe2SO4, vitamin C, and hydrogen peroxide. The release of thiobarbituric-acid-reactive substances (TBARS, lipid peroxidation) and lactate dehydrogenase (LDH, membrane damage) was measured photometrically. Various estradiol doses and vitamin E, serving as control with an established anti-oxidative capacity, were applied either upon each exchange of medium and during radical production (strategy 1) or only during radical production (strategy 2). In chondrocytes incubated according to strategy 1, the production of TBARS and LDH release were significantly suppressed by 10(-10)-10(-4) M estradiol or by vitamin E. Under strategy 2, the production of TBARS was significantly suppressed at estradiol concentrations higher than 10(-6) M, whereas LDH release was inhibited at concentrations of 10(-6)-10(-4) M. Vitamin E showed no significant effects. As repeated application of estradiol and vitamin E produced the best results, estradiol, like vitamin E, was speculated to accumulate in the plasma membrane and to decrease membrane fluidity resulting in protection against lipid peroxidation (non-genomic effect). Thus, in contrast to the neuroprotective effect of 17beta-estradiol in supraphysiological doses reported recently, the anti-oxidative potential of estradiol appears to protect articular chondrocytes from ROS-induced damage when the hormone is given repeatedly in a physiological range. Decreased estradiol levels may therefore contribute to menopausal OA in the long term.

Selective inhibition of pinacidil effects by estrogen in guinea pig heart

“…Interestingly, application of 17-h-estradiol in male guinea pigs decreased, while tamoxifen in female guinea pigs increased concentration of the heart form of LDH (H-LDH). Suppression of LDH production by estrogen has already been demonstrated [17,18]. Taken together, our data indicate that estrogen modulates the effects of pinacidil specifically, and additionally downregulates production of H-LDH.…”

The phytoestrogens daidzein and genistein enhance the insulin-stimulated sulfate uptake in articular chondrocytes

“…Recently, we have shown that 17β-estradiol possesses antioxidative properties and prevents membrane damage of bovine articular chondrocytes monitored by LDH release (Claassen et al 2005). Since the effects of daidzein and genistein reported here differ from those of 17β-estradiol, antioxidative mechanisms stabilizing the plasmatic membrane are probably not involved.…”

Sex difference in the heat shock response to high external load resistance training in older humans

“…This confers estrogen the property of an antioxidant. In this regard, estrogen has been shown to protect various cell types during acute stress by increasing the anti-oxidant properties of the cells (57,58). Further, Wiseman (59) found that the administration of estrogen inhibited lipid peroxidation in microsomal and liposomal systems.…”