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.
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.
This study compared the effect of low‐fat diet (LFD) and high‐fat diet rich in corn oil (HFD‐CO) on left ventricular (LV) fibrosis in rats and examined their effect of angiotensin II (ANG II), JAK/STAT, and TGF‐1β/smad3 pathways. As compared to LFD which didn't affect any of the measured parameters, HFD‐CO‐induced type 2 diabetes phenotype and increased LV collagen synthesis. Mechanistically, it increased LV levels of ROS, ANG II, ACE, IL‐6, s‐IL‐6Rα, TGF‐β1, Smad‐3, and activities of JAK1/2 and STAT1/3. AG490, a JAK2 inhibitor, partially ameliorated these effect while Losartan, an AT1 inhibitor completely abolished collagen synthesis. However, with both treatments, levels of ANG II, IL‐6, and s‐IL‐6Rα, and activity of JAK1/STAT3 remained high, all of which were normalized by co‐administration of NAC or IL‐6 neutralizing antibody. In conclusion: HFD‐CO enhances LV collage synthesis by activation of JAK1/STAT3/ANG II/TGF‐1β/smad3 pathway.
We report that chronic consumption of a high‐fat diet rich in corn oil (HFD‐CO) induces diabetes mellitus phenotype 2 associated with left ventricular (LV) cardiac fibrosis in rats. The findings of this study show that HFD‐CO, and through the increasing generation of ROS and IL‐6 levels and shedding, could activate LV JAK1/2‐STAT1/3 and renin‐angiotensin system (RAS) signaling pathways, thus creating a positive feedback between the two which ultimately leads to activation of TGF‐1β/Smad3 fibrotic pathway. Herein, we also report a beneficial effect of the antioxidant, NAC, or IL‐6 neutralizing antibody in preventing such adverse effects of such HFD‐CO. However, this presents a warning message to the current sudden increase in idiopathic cardiac disorders, especially with the big shift in our diets toward n‐6 PUFA.
Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.
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