This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i.p., daily). All treatments were administered for 3 weeks. Administration of ghrelin to MI rats improved left ventricle (LV) architecture and restored cardiac contraction. In remote non-infarcted areas of MI rats, ghrelin reduced cardiac inflammation and lipid peroxidation and enhanced antioxidant enzymatic activity. In addition, independent of the growth factor/insulin growth factor-1 (GF/IGF-1) axis, ghrelin significantly increased the phosphorylation of JAK2 and Tyr702 and Ser727 residues of STAT3 and inhibited the phosphorylation of JAK1 and Tyr701 and Ser727 residues of STAT1, simultaneously increasing the expression of BCL-2 and decreasing in the expression of BAX, cleaved CASP3, and FAS. This effect coincided with decreased expression of SOCS3. All these beneficial effects of ghrelin, except its inhibitory action on IL-6 expression, were partially and significantly abolished by the co-administration of AG490. In conclusion, the cardioprotective effect of ghrelin against MI-induced LV injury is exerted via activation of JAK2/STAT3 signaling and inhibition of STAT1 signaling. These effects were independent of the GF/IGF-1 axis and could be partially mediated via inhibition of cardiac IL-6.

No abstract

No abstract

Testosterone improved cardiac contractility and shortened QT and QTc intervals in ORX rats. An effect that might be dependent of reduction in oxidative stress and enhancement of Kir2.1 channels but independent of Nav1.5 channel protein.