Effect of melatonin on peripheral neuropathic pain in diabetic rat

Diabetes mellitus is often accompanied by chronic neuropathic pain. Studies indicate that oxidative stress has an important role in the appearance of neurological and behavioral changes in diabetes. Necessitating researching therefore the antioxidants effects in alleviation of diabetic neuropathic pain. In this study, 32 male Wistar rats weighing 200 +/- 20 g were used, and were divided into four groups: Control[C], melatonin[M], diabetic[D] and melatonin-treated diabetic[MD]. Experimental diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin [STZ]. Melatonin was injected [10 mg/kg/day, i.p.] for 2 weeks, after 21 days of diabetes induction. At the end of administration period, nociceptive biphasic behavior in rats was assessed using the 0.5% formalin test, and then observed for up to 60 min, according to spontaneous flinching and licking responses. In this study, lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in spinal L4-S3 dorsal root ganglia. Experimental data were then statistically analyzed Formalin-evoked flinching increased in both acute and chronic phases of pain in diabetic rats as compared to non-diabetic ones, whereas administration of melatonin reduced flinching frequency in both phases in MD rats. Total time of licking in diabetic rats was significantly [p < 0.05] more than the control rats in both acute and chronic phases of pain melatonins injection significantly reduced this time in both phases of pain in the MD as compared D group, whereas was no significant difference between M and C rats in the indices mentioned. Assessment of dorsal root ganglia homogenates indicated an increase in Lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the D group as compared to the controls [C]. While melatonin administration ameliorated these in diabetic rats. Results suggest that oxidative stress contributes to appearance of pain in diabetes and melatonin, as an antioxidant, is effective in reducing the acute and chronic pain in diabetic rats

[Effect of melatonin on sexual behavior in male diabetic rats]

Several clinical studies indicate deterioration of sexual behavior in diabetic patients. The pathophysiological mechanisms of diabetic sexual impotence remain obscure. In this study the therapeutic effects of melatonin on sexual behavior were investigated through the central serotonergic system in diabetic rats. In this study, 30 male adult Wistar rats, weighing 200 +/- 20 g, were used. Animals were divided into three groups, the controls [C], diabetic [D] and the melatonin-treated diabetic [M] group. Experimental diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin. Melatonin was injected [10 mg/kg i. p.] after 3 days of streptozotocin injection for 30 days. At the end of the administration period, the sexual behavior of each male rat to an ovariectomized female rat was assessed for 40 min. Serotonergic type 2 [5-HT2A] receptor activities were investigated through spontaneous WDS behavior, and experimental data were statistically analyzed. First mount, first intromission and first ejaculation latencies significantly [p<0. 05] increased in diabetic rats as compared to controls. Melatonin treatment significantly [p<0. 05] reduced these responses in the M group, compared to the D one. Also the number of mounts, intromissions and ejaculations significantly [p<0. 05] decreased in diabetic rats compared to controls. Administration of melatonin significantly [p<0. 05] increased these activities in the M group as compared to the D one. Calculation of copulatory efficiency and the sexual activity index of each rat indicate that reproductive activity in diabetic rats was significantly [p<0. 05] less than other two groups. The number of WDS responses was significantly [p<0. 05] different in all three groups. Sexual dysfunction in diabetic animals was accompanied by decreasing of 5-HT2A receptor activities, and melatonin prevented the diabetes-induced sexual impotence by modulating of central serotonergic system activity

[Impact of two selected non-steroidal anti-inflammation drugs flunixin and ketoprofen on peroxynitrite-induced inflammation and serum levels of cortisol and glucose]

Peroxynitrite, produced naturally in the body from a reaction between nitric oxide and superoxide anion, possess destructive effects against microorganisms. In excess concentrations, however, it may also lead to cellular damage and inflammatory reactions in the host. Non - sterodial anti inflammation drugs [NSAIDs] are used widely in therapy for their antiinflammatory, analgesic and antipyretic properties. Meanwhile, their adverse effects on endocrine functions should be taken into account. This project aims at the following goals: 1] establishing a new animal model of peroxynitrite-induced inflammation, 2] studying the effect of two selected NSAIDs on these parameters.3] investigating the possible effect of this oxidant on the blood levels of cortisol and glucose. 24 male guinea pigs were divided into 4 groups [6 animals in each group]. Three groups were injected peroxynitrite and the last group, control group, given physiological salt solution in the paw subcutaneously. Following induction of a local inflammatory response, flunixin meglumine and ketoprofen [0.5 mg/0.5 ml] were injected to second and third groups, 5 times with 12h intervals. First and fourth groups were injected saline solution with the same manner. Animals were anesthetized with thiopental [60 mg/kg, i.p.] and a blood sample was collected by heart puncture. The glucose and cortisol levels of blood were determined by routine laboratory techniques. Blood glucose concentration in the animals that only injected peroxynitrite was less than the control group. In addition, groups which were given drugs had statistically higher levels of glucose in their blood more than the others. Although, cortisol levels were lower in the test groups compared to the control group, these differences were not significant statistically. The results of current study showed that both peroxinitrite and NSAIDs decreasethe cortisol levels of blood. These findings can be a possible explanation for the lower levels of cortisol in the blood of patient who receive nitro glisirin as well as osteoarthritis patients that mainly take NSAIDs. In the study, the glucose levels of blood in animals given drugs were more than the control groups