Mahmoud Alkhateeb

Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression.

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.

Effect of testosterone replacement therapy on cardiac performance and oxidative stress in orchidectomized rats

To investigate the effects of testosterone on myocardial contractility, oxidative stress status and expression of sodium channel protein (Nav1.5) and inward rectifying K channels (Kir 2.x) in normal and orchidectomized (ORX) rats.

Exercise protects against obesity induced semen abnormalities via downregulating stem cell factor, upregulating Ghrelin and normalizing oxidative stress

Increased oxidative stress and hormonal imbalance have been hypothesized to underlie infertility in obese animals. However, recent evidence suggests that Ghrelin and Stem Cell Factor (SCF) play an important role in fertility, in lean individuals. Therefore, this study aimed at investigating whether changes in the levels of Ghrelin and SCF in rat testes underlie semen abnormal parameters observed in obese rats, and secondly, whether endurance exercise or Orlistat can protect against changes in Ghrelin, SCF, and/or semen parameters in diet induced obese rats. Obesity was modelled in male Wistar rats using High Fat Diet (HFD) 12-week protocol. Eight week-old rats (n=40) were divided into four groups, namely, Group I: fed with a standard diet (12 % of calories as fat); Group II: fed HFD (40 % of calories as fat); Group III: fed the HFD with a concomitant dose of Orlistat (200 mg/kg); and Group IV: fed the HFD and underwent 30 min daily swimming exercise. The model was validated by measuring the levels of testosterone, FSH, LH, estradiol, leptin, triglycerides, total, HDL, and LDL cholesterol, and final change in body weight. Levels were consistent with published obesity models (see Results). As predicted, the HFD group had a 76.8 % decrease in sperm count, 44.72 % decrease in sperm motility, as well as 47.09 % increase in abnormal sperm morphology. Unlike the control group, in the HFD group (i.e. obese rats) Ghrelin mRNA and protein were elevated, while SCF mRNA and protein were diminished in the testes. Furthermore, in the HFD group, SOD and GPx activities were significantly reduced, 48.5±5.8 % (P=0.0012) and 45.6±4.6 % (P=0.0019), respectively, while TBARS levels were significantly increased (112.7±8.9 %, P=0.0001). Finally, endurance exercise training and Orlistat administration individually and differentially protected semen parameters in obese rats. The mechanism includes, but is not limited to, normalizing the levels of Ghrelin, SCF, SOD, GPx and TBARS. In rat testes, diet induced obesity down regulates SCF expression, upregulates Ghrelin expression, and deteriorate oxidative stress levels, which are collectively detrimental to semen parameters. Exercise, and to a lesser extent Orlistat administration, protected effectively against this detrimental effect.

The impact of dehydroepiandrosterone on indomethacin-induced gastric lesions in rats

UNLABELLED Gastric ulcer is a common gastrointestinal disease. One suggested mechanism is increased oxidative stress. Puplished data showed that dehydroepiandrosterone (DHEA) may limit oxidative stress and lipid peroxidation. OBJECTIVE To investigate the protective effect of DHEA on indomethacin-induced gastric ulcers in rats. METHODS Forty male rats were randomly divided into four groups: l) CONTROL GROUP receive the vehicle, 2) DHEA-treated group, 3) Indomethacin-induced ulcer group and 4) DHEA pretreated (prior to indomethacin) group. At the end of the experiment, rats were killed and the gastric contents were collected to determine the pH and acid concentration. Gastric mucosa was examined macroscopically and then parts of the tissues were collected for histopathological examination. Other parts of the gastric mucosa were homogenized to measure the levels of lipid peroxidation and oxidative stress parameters. RESULTS Indomethacin-treated rats showed increased gastric acidity, acid concentration and ulcer index as compared to control rats. This is confirmed by histopathological studies. DHEA pre-treatment proir to indomethacin administration ameliorated all changes seen in the ulcered group. CONCLUSION DHEA has a protective effect against indomethacin-induced gastric ulcers through decreasing acid secretion, prevention of lipid peroxidation and improving endogenous gastric antioxidant system.

Exhaustive exercise and vitamins C and E modulate thyroid hormone levels at low and high altitudes

Thyroid hormones play an important role in cell growth and differentiation and regulation of oxygen consumption and thermogenesis. The effect of altitude and vitamin supplementation on thyroid hormone levels in animals or humans performing acute exhaustive exercise have not been investigated before. Therefore, we thought to test whether exhaustive exercise-induced stress with antioxidant supplementation was capable of modulating the level of thyroid hormones at different altitudes. Serum levels of T4 (Thyroxin), T3 (Triiodothyronine), and TSH (Thyroid Stimulating Hormone) were measured in rats (N=36) born and bred in low altitude (600 m above sea level) and high altitude (2200 m above sea level) following forced swimming with or without vitamins C and E (25 mg/kg) pre-treatments. Thyroid levels were significantly decreased in resting rats at high altitude compared to low altitude, and swimming exercise moderately increased T3 and TSH at both high and low altitudes, whereas T4 was markedly increased (62 %) at low altitude compared to a moderate high altitude increase (28 %). Co-administration of vitamins C and E augmented the observed forced swimming-induced thyroid release. However, the conversion of T4 to T3 was reduced in both altitude areas following swimming exercise and vitamin pre-treatment had no effect. We conclude that acute stress induced thyroidal hormones in rats, which was augmented by antioxidant drugs in both high and low altitude areas. These findings may play an important role in the human pathophysiology of thyroid gland at different altitudes.

Ghrelin Improves the Fine Structure of Atrial Natriuretic Factor (ANF) Granules and Intercalated Disc Junctions in Experimentally-Induced Myocardial Infarction in Rats

Ghrelin is a novel growth hormone-releasing peptide administered to treat myocardial infarction (MI). However, the underlying mechanism of its protective effects against MI remains unclear. A total of sixty healthy Sprague Dawley male rats we re included. The first one is the sham-operated control group were the rats that underwent the same surgical used to induce MI but without t ying the left anterior descending coronary artery (LAD) and received normal saline (0.5 ml) as vehicle; the second MI model group were rats w ith LAD ligation and received normal saline (0. 5 ml) and the third one is MI+ghrelin group were rats that were exposed to surgery to i nduce MI but received ghrelin (100 μ/kg, orally, 2x/day). At the end of the experiment after 21 days post-MI, rats were sacrificed and processed for ultrastructural demonstration. Our experiment showed that ghrelin inhibited cardiomyocyte apoptosis. Concomitant administration of gh el n with MI treated rats of this study appeared to show a considerable protection of the atrial tissues. This study revealed that t he sarcoplasm was occupied by normal myofibrils with clear striations and others appeared with minor disruption. Normal distribution of atrionatr iuretic factor (ANF) granules and well preserved mitochondrial integrity (preserved cristae, normal size and shape), nucleus chromatin arrange ment and striated pattern of clear bands (Z and H) compared to the MI group. Intact intercalated disc with clear identification of fully formed fascia adherence and desmosomes with a reconstruction of gap junction (nexus) was also noticed. Atrial myocytes after myocardial infar tion is often associated with subsequent heart failure, which could lead to a fatal outcome. In a rat model of experimental myocardial infarction, peripheral ghrelin administration attenuated myocyte dysfunction, well-preserved desmosome, adherent and gap junction of the in tercalated disc and normally distributed ANF granules.