Zehra Kurcer

Melatonin protects from ischemia/reperfusion‐induced renal injury in rats: this effect is not mediated by proinflammatory cytokines

Abstract:  The pathophysiologic mechanisms leading to acute ischemic renal failure are not completely understood. Melatonin, a compound with well‐known antioxidant properties, reduces IR‐induced renal injury. The purpose of the present study was to investigate the changes in levels of tumor necrosis factor (TNF)‐α, IL‐β, and IL‐6 in postischemic reperfused renal tissue, and to determine whether the protective effect of melatonin is related the modulation of the production of these inflammatory molecules. Male Wistar albino rats were unilaterally nephrectomized and subjected to 1 hr of renal pedicle occlusion followed by 2 hr or 24 hr of reperfusion. Melatonin (10 mg/kg, i.p.) or vehicle was administrated at 10 min prior to ischemia. After 24 hr of the reperfusion, following decapitation, kidney samples were taken both for histologic examination and for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, total antioxidant capacity (TAC), total oxidative stress (TOS), creatinine, and blood urea nitrogen (BUN). These were measured in serum samples. TNF‐α, IL‐β, and IL‐6 were measured in kidney samples after 2 hr of reperfusion. IR caused a significant increase in renal MDA, MPO, TOS, creatinine, and BUN while decrease TAC without any change in TNF‐α, IL‐β, and IL‐6 levels. Melatonin treatment reduced the biochemical indices without any change in the cytokine levels and ameliorated histopathologic alterations induced by IR. The protective effect of melatonin on IR‐induced renal injury is related to its antioxidant properties but not to proinflammatory cytokines.

Melatonin improves methanol intoxication‐induced oxidative liver injury in rats

Abstract:  This study was performed to evaluate the effect of melatonin on methanol‐induced liver injury. We evaluated the levels of malondialdehyde (MDA), protein carbonylation (PC), myeloperoxidase (MPO) activities and to assess lipid peroxidation, protein oxidation, neutrophil accumulation and nitrite which is a stable end product of nitric oxide respectively. We also studied superoxide dismutase, catalase, and glutathione peroxidase activities of liver tissue to evaluate the changes in the antioxidant status. Histopathological alterations were also determined. The experiment was performed on Wistar rats, which received intragastric 3 g/kg methanol as a 50% solution in isotonic saline once. After 6 and 24 hr all the drug received and intoxicated rats were killed under anesthesia. Pretreatment with melatonin (10 mg/kg) decreased the MDA levels significantly, restored the PC levels to the control, prevented the increase of nitrite level and MPO activity significantly and reversed to the control levels, prevented the reduction in all of the antioxidant enzyme activities. Additionally in melatonin treated group piecemeal necrosis, lobular lytic necrosis, and portal inflammation returned to normal histologic appearances when compared with methanol administration. In conclusion, melatonin has protective effects against methanol‐induced hepatic injury.

Nasal polyp diseases in allergic and nonallergic patients and steroid therapy

Objective To investigate widespread disease causes, cellular-structural differences, and steroid response of nasal polyps (NPs). Method Study group consisted of NPs, allergic-NPs, NPs with steroid therapy (ST), antrochoanal polyp (ACP), and controls. We investigated stromal eosinophil, mast cell, CD4+ and CD8+ cell counts and presence of squamous metaplasia, Ki-67 expression, intraepithelial eosinophils-mast cells, epithelial damage, edema, fibrosis, hyalinization, polymorphonuclear leukocyte, and glandular hyperplasia. Results In allergic-NPs, intraepithelial eosinophils and epithelial damage CD4+ were significantly higher than NPs and also, eosinophils, mast cells, intraepithelial eosinophils, and epithelial damage were significantly higher than ACP. Only stromal eosinophilic infiltration was significantly higher in NPs than ACP. There was significant increased glandular hyperplasia and decreased intraepithelial eosinophils, mast cells, CD4+ cells, squamous metaplasia, and epithelial damage with ST in allergic-NPs. There were no significant differences with ST in NPs. Conclusion NPs in allergic and nonallergic patients may differ in their histology and in their histologic responses to ST. EBM rating: B-3b

Effect of lycopene on caspase-3 enzyme activation in liver of methanol-intoxicated rats: comparison with fomepizole.

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. This study was performed to evaluate the effect of lycopene on methanol-induced liver injury and to compare the results with those after fomepizole, which is used in treatment of methanol intoxication. Experiments were carried out with 30 female Wistar rats weighting 180-200 g. Rats were injected with a intraperitoneally dose of 3 g/kg methanol as a 50% solution in isotonic saline once for intoxication. Rats were pretreated with fomepizole (50 mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24 hours all the drug-treated and intoxicated rats were sacrificed under anesthesia. Malondialdehyde (MDA) levels were determined in order to assess lipid peroxidation, and caspase-3 activity was determined by immunostaining of liver tissues to evaluate apoptosis. Methanol administration significantly increased the MDA level and caspase-3 activity in liver. Pretreatment with lycopene and/or fomepizole decreased the MDA levels significantly. Similarly, lycopene and fomepizole decreased methanol-induced caspase-3 activity. The findings of the present study demonstrate that methanol intoxication causes hepatic toxicity in rats and that this is likely a result of reactive oxygen species and apoptosis induction. Lycopene has protective effects against methanol-induced hepatic injury similar to fomepizole. It was demonstrated for the first time that both lycopene and fomepizole prevent methanol-induced hepatic injury by reducing the increase of lipid oxidation and caspase-3 activation.

Melatonin attenuates α-adrenergic-induced contractions by increasing the release of vasoactive intestinal peptide in isolated rat penile bulb

The effects of melatonin on α-adrenergic-induced contractions caused by electrical field stimulation (EFS) or the α1-adrenoceptor agonist phenylephrine (Phe) were investigated in isolated rat penile bulb. Melatonin as well as melatonin receptor agonists N-acetylserotonin and 2-iodomelatonin and melatonin antagonist luzindole attenuated the EFS-induced contractions and the concentration-response curve to Phe. The effect of melatonin on Phe-induced contractions was completely reversed by treatment with tetrodotoxin, guanethidine or vasoactive intestinal peptide (VIP) antagonist. On the other hand, pretreatment with N-methyl-l-arginine, atropine, and luzindole did not reverse the effect of melatonin. Thus, we demonstrated that melatonin at nanomolar concentrations inhibits the α-adrenergic responses in isolated rat penile bulb. Since α-adrenoceptor blocking agents are known to interfere with detumescence of the erect penis, serum levels or administration of this pineal hormone may affect erectile function. This effect of melatonin may be the result of its allosteric interaction with the presynaptic receptors on VIPergic neurons, which are affected by sympathetic transmission, and then an increase in VIP release from these neurons.

Morphological Changes and Vascular Reactivity of Rat Thoracic Aorta Twelve Months After Pinealectomy

ABS TRACT Objective: Melatonin, a hormone produced by the pineal gland, has been suggested to protect against development of hypertension and atherosclerosis. In this study, the effects of longterm melatonin deficiency for twelve months after pinealectomy on the α-adrenergic-contractions induced by phenylephrine, endothelium-dependent relaxation responses to acetylcholine and the morphological changes in the rat thoracic aorta were studied. Material and Metods: Rats were pinealectomized twelve months before the beginning of the vasomotor studies. Rings of arteries were mounted in isolated tissue baths for the measurements of isometric contractile force. The contractile responses to phenylephrine and endothelium-dependent relaxation responses to acetylcholine in the vessels were evaluated. Endothelial function was evaluated by vascular relaxation to acetylcholine. Histological examinations demonstrated the alterations of tunica media in the vessels of pinealectomized rats. Results: Thick and thin areas were observed in the transverse sections of vessels and the ratio of the widest media thickness to the narrowest was found significantly increased in pinealectomized group (2.85 ± 0.56) when compared to the control group (1.65 ± 0.10). In addition, α-smooth muscle actin and elastic lamellae staining of the media were attenuated in pinealectomized rats. Although contractile responses of vessels to phenylephrine in pinealectomized rats were lower than control group, significant difference was found for only one concentration (3x 10-8 mol l-1) of phenylephrine. There was no difference between the relaxation responses to acetylcholine in pinealectomized and control groups. Conclusion: These results show that long-term melatonin deficiency may cause some morphological changes in the tunica media of vessels. However, the function of endothelium and vascular responsiveness to ∝-adrenergic stimulus seem to be mostly protected.