Effect of retinoic acid on type I diabetes: Streptozotocin-induced rat model

To evaluate the effect of all trans retinoic acid [atRA] on differentiation/transdifferentiation of pancreatic duct/acinar cells into insulin secreting beta-cells in diabetic rats. 64 adult male rats divided into four groups. Normal control, diabetic control, atRA-I: diabetic rats treated with atRA [0.1 mg/kg/day, subcutaneously] and atRA-II: diabetic rats treated with atRA [2.5 mg/kg/day, subcutaneously] for 1, 2 and 4 weeks. The levels of glucose and insulin were measured. Histopathological, immunohistochemical examination of pancreas and RT-PCR of insulin mRNA were done. atRA led to an improvement in the level of glucose and insulin in both doses and at the different time points when compared with diabetic control. Histopathological examination of the pancreas revealed that atRA in both doses and at different time points nearly restored the normal appearance of the islets of Langerhans. Interestingly, some islets of Langerhans were found closely related to the interlobular ducts and the acinar epithelium. Mitotic figures were observed in the epithelium of the interlobular ducts and acinar cells and inside the islets of Langerhans especially with high dose. The immunohistochemical revealed strong insulin-immunoreactivity in the cytoplasm of the beta-cells and in the cytoplasm of the isolated cells which are closely related to the acini. Also, insulin mRNA expression showed dense band illumination similar to normal control. Retinoic acid may induced significant increase in insulin level and its mRNA, decrease glucose level and increased beta-cells regeneration through increased pancreatic duct and/or acinar cells differentian/transdifferentiation and increased proliferation of fbeta-cells in diabetic rats

inhibitory effects of melatonin on vascular reactivity: possible role of vasoactive mediators

The aim of this study was to investigate the effect of melatonin [MEL] on isolated rabbit aortic rings and its role in the vascular reactivity to contractile agents, noradrenaline [NA] and phenylephrine [PHE], as well as the relaxant agents [acetylcholine and sodium nitroprusside]. In addition, the levels of nitric oxide [NO], cyclic guanosine monophosphate [cGMP], total calcium, lipid peroxides, superoxide dismutase [SOD] and glutathione [GSH] were also investigated in the tissue homogenates of rabbit aortic rings pre-incubated [20 min] in MEL with and without contractile agents. The result revealed that MEL has an endothelium dependent vaso-relaxant effect and potentiated significantly the vaso-relaxant effect of acetylcholine. Moreover, MEL [10-4M] had a significant inhibitory effect on the contractile responses of aortic rings to both NA and PHE. In comparison with the control tissue rings, the levels of lipid peroxides were significantly increased; while those of GSH and SOD activities were significantly decreased in the tissue homogenates of aortic rings pre-incubated [20 min] in NA or PHE. In addition, the levels of NO and cGMP were significantly lower in the tissue rings pretreated with NA and PHE, respectively. The levels of total calcium were significantly increased in only tissue rings pretreated with NA. The levels of lipid peroxides were significantly decreased; while those of GSH, NO, cGMP and SOD activities were significantly increased in tissue homogenates of aortic rings incubated [20 min] in MEL [10-4 M] in comparison with ring tissues incubated in NA or PHE alone. In aortic rings incubated In MEL + PHE, the levels of lipid peroxides were significantly lower; while those of GSH, cGMP and SOD activities were significantly higher than their levels in ring tissues incubated in PHE. In aortic rings incubated in MEL + NA, the levels of lipid peroxides and total calcium were significantly lower; while those of NO were significantly higher than their levels in ring tissues incubated in NA alone

Impact of oxidative stress and smoking on muscle fatigue markers during a single bout of exercise

In this study, 18 male well-trained physical education faculty senior students were randomly selected and grouped into smoker [5 active + 4 passive] and non-smoker [9] student groups. Plasma was collected immediately before and after a single bout of endurance track running exercise. A selected number of least invasive plasma indices of muscle fatigue [lactate and activity of lactate dehydrogenase, LDH, and xanthine oxidase, XO]. Oxidative stress [thiobarbituric acid reactive substances [TBARS], nitric oxide [NO], total iron and [Fe2+]], antioxidation [total antioxidant activity [TAOA], urate, ascorbate total zinc [Zn2+] and selenium [Se2+]] and superoxide dismutase activity [SOD] were measured using atomic absorption flame photometric and colorimetric techniques. Smoking index was calculated and plasma cotinine, the endogenous nicotine metabolic indicator, was measured using ELISA technique. Exercise induced a significant increase in muscle fatigue and peroxidative indices [lactate, LDH, XO, TBARS, NO and Fe2+] and a significant decrease in Se2+, Zn2+ and ascorbate. There was a significant increase in TAOA and SOD and a nonsignificant increase in urate in the two groups. Smokers showed significantly higher basal peroxidative and lower antioxidation indices compared with nonsmokers, a picture that was exacerbated post-exercise. These changes could not be reflected significantly on the indices of exercise and cardiorespiratory endurance

velopment and characterization of a potential sustained release melatonin formulation: a possible modulatory influence of melatonin on glutathione s-transferases enzymes in rats

In this study, melatonin treatment in rats produced a significant elevation in hepatic cytosolic activity levels of GSTs and GSH-Px as well as glutathione [GSH] content with a reduction in lipid peroxide compared with the corresponding controls. In this study, a new preparation of melatonin "melatonin resinate-loaded microcapsules" was used. It prolonged and sustained the effect of melatonin up to 6 hours instead of 24 minutes [the half life in pure melatonin]. These new preparations produced a significant marked effects of melatonin on induction of GSTs and GSH-Px enzymes systems. It was concluded that melatonin particularly melatonin resinates loaded microcapsules induced the GSTs and GSH-Px enzyme systems in liver and this effect was potent than phenobarbitone. It was also suggested that melatonin exerts its antioxidants protective effects by stimulating the activities of detoxifying enzymes and may be through its direct antioxidant effects

Effect of propofol on perception of pain in mice: study on the mechanism of action

Propofol is an intravenous anesthetic used clinically. The latencies of pain threshold of different subhypnotic doses [12.5, 25 and 50 mg kg-1] of propofol administrated intraperitoneally [ip] into mice were measured by using hot plate method technique. The possible mechanism of pain control by propofol was also investigated through blocking beta- endorphin receptors and measuring serum level of beta-endorphin. Morphine [1.5 mg kg-1, ip] was used as reference of reduction of pain sensation. The results showed that propofol in doses of 25 and 50 mg kg-1 increased significantly the latency of pain threshold, but the lower dose [12.5 mg kg-1] failed to produce any significant change. This indicated that propofol reduced pain sensation and this effect is dose-dependent. It was also observed that propofol prevents hyperalgesia produced by prostaglandin [PGE2] [0.5 mg kg-1, ip]. For investigating the mechanism of action of propofol, pretreatment with naloxone [1.0 mg kg-1, ip] abolished significantly the antinociceptive action of propofol. Furthermore, serum level of beta- endorphin was increased significantly after propofol injection particularly at the peak time of propofol action. Serum level of corticosterone was also increased significantly at the time of beta- endorphin release

Effects of melatonin on blood cells

Daily subcutaneous injection of melatonin in a dose of 200 ug [0.5 ml] for seven days in one group of rats and for twenty-one days in another group produced an increase in the total number of WBCs, neutrophils, lymphocytes, eosinophils and basophils. These changes were marked in the twenty-one days treated group of rats. In seven days treated group, melatonin produced an increase in RBCs count and PCV% associated with a decrease in MCH and MCHC. In twenty-one days treated group, melatonin decreased PCV, Hb, MCV, MCH and MCHC. These findings suggested an immunostimulatory role for melatonin