Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats

Abstract

Ovariectomy constitutes a commonly used model in rats and mice for human menopause. After ovariectomy, an imbalance between oxidant production and antioxidant levels appears in favour of the former, with increased oxidative stress and consequently an acceleration of ageing. In the present work, the levels of reduced glutathione (GSH), a relevant antioxidant, and oxidized glutathione (GSSG), an oxidant compound, as well as lipid peroxidation (through malondialdehyde (MDA) levels), were studied in liver, heart, kidney and spleen homogenates of old (24 months of age) unovariectomized and ovariectomized female Wistar rats. The results showed a significant increase of the GSSG/GSH ratio, a marker of oxidative stress, and higher MDA production in all the studied organs of ovariectomized rats as compared with unovariectomized animals. These data confirm the idea that ovariectomy accelerates the ageing process. Administration of growth hormone (GH), melatonin (MEL) and oestrogens (OE), as well as soybean phytoestrogens (PE) for 10 weeks, between 22 and 24 months of age, was able to decrease oxidative stress in the investigated organs of ovariectomized old rats, therefore slowing down the ageing process in those animals.

Relationship between Oxidative Stress and Cardiomyopathic Changes in Ovariectomized Rats

“…Sex hormones produce a natural antioxidant effect. The sudden withdrawal of these enzymes, especially estrogens, as a result of having an ovariectomy, weakens the balance of the oxidant/antioxidant system [20,21]. In our study, the ovariectomy procedure resulted in an increase in the amount of CAT and SOD but a decrease in the amount of antioxidants such as GSH.…”

“…Urata et al [32] reported that estradiol was directly linked to GSH synthesis. Therefore, ovariectomy and the subsequent estrogen loss might have significantly altered this stimulatory effect of estradiol on GSH synthesis [20]. In the present investigation, ovariectomy triggered an imbalance in the pro-oxidant status of GSH in the heart tissues of the rats.…”

“…Ovariectomy has been shown to cause an increase in oxidative stress and peroxide production [20,21]. Experimental evidence has revealed that estrogens are antioxidant and cardioprotective hormones that positively modulate the activities of antioxidant enzymes [20,22,23].…”

“…Experimental evidence has revealed that estrogens are antioxidant and cardioprotective hormones that positively modulate the activities of antioxidant enzymes [20,22,23]. It is suggested that, because of the reduced estrogen levels after menopause, women lose an important cardiovascular protective mechanism and are therefore at greater risk of developing heart disease [24].…”

“…These results could be attributed to the fact that female rats maintain a certain degree of estrogen secretion until very late in their lives [46], and that for this reason unovariectomized rats are partially protected against some age-related changes, while this is not the case for rats that had undergone an ovariectomy [20]. …”