The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female rats

Abstract

The antioxidant activity of some compounds buffer the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Recent studies documented that raloxifene has antioxidant properties in vitro. However, there are limited animal studies available to show raloxifene's antioxidant properties. We aimed to investigate the effects of raloxifene on antioxidant enzymes such as SOD, CAT and GPX, TrxR and the levels of GSH and MDA in heart, liver and brain cortex of ovariectomized female rats. Female Sprague Dawley rats weighing 300-350 g (n=24) were divided into three groups: (I) Eight non-ovariectomized rats were used as naive controls without any treatment (non-ovariectomized group, n=8). Five weeks after ovariectomy, (II) Ovariectomized placebo group (n=8) was given physiological saline, and (III) Raloxifene group (n=8) was given raloxifene 1 mg/kg sc. daily for 12 days. Ovariectomy induced significant increases on SOD, GPX, CAT activity and MDA levels in brain, heart and liver tissues compared to non-ovariectomized rats ( p<0.05). Raloxifene treatment led to decreased levels of SOD activity in heart, GPX activity in brain and CAT activity in liver tissue when compared to ovariectomized group ( p<0.05) but there was no change in activity of TrxR in all groups. The levels of MDA in brain, heart and liver tissues increased in ovariectomized group when compared to non-ovariectomized rats ( p<0.05). Raloxifene had a significant attenuating effect on the levels of MDA in brain and heart tissues. Our results also indicate that the levels of GSH in brain, heart and liver tissue decreased when compared to non-ovariectomized rats. Raloxifene treatment was observed to significantly increase the levels of GSH in brain and heart tissues ( p<0.05). However, there were insignificant differences for the GSH levels in liver tissues of ovariectomized placebo or raloxifene groups. In conclusion, our results demonstrate that raloxifene may be more effective against oxidative stress in heart and brain than in liver tissue.

The Effects of Caffeic Acid Phenethyl Ester (CAPE) on TNBS-induced Colitis in Ovariectomized Rats

“…Bilateral ovariectomies were performed under intraperitoneally administered ketamine and xylazine HCl anesthesia using a dorsal approach in all animals; the rats were kept for 1 month to recover and adapt to the absence of endogenous estrogen. The 1-month duration for ovariectomized animals was previously used in the same experimental model successfully, and it has been reported that this protocol produced postmenopausal changes in ovariectomized animals [27,28].…”

Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen‐Deficient Rat

“…RAL improves the endothelial function in ovariectomized (OVX), aged, or hypertensive rats, ameliorates the hypertension-induced endothelial dysfunction by reducing the production of reactive oxygen species, and enhances endothelial nitric oxide- (NO-) dependent vasodilatation in vitro. Moreover, RAL causes direct vasodilatation [15]. It reduces the increased cardiovascular risk in patients with osteoporosis, although the outcomes of the RUTH trial showed that RAL did not affect the overall risk of coronary heart disease in elderly women.…”

Mitochondria from distinct tissues are differently affected by 17β-estradiol and tamoxifen

“…Intracellular GSH is converted into GSSG by glutathione peroxidase, which catalyzes the reduction of H 2 O 2 and various hydroperoxides. Konyalioglu et al [51] reported that raloxifene (another selective estrogen receptor modulator) treatment significantly increases the levels of GSH in brain and heart tissues of ovariectomized females although no significant differences are found in liver tissue.…”