In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg(-1) rat day(-1); orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme activities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung.
Despite antiproliferative effects of melatonin on cultured tumor cells, its effects on normal cells are less clear. The action of melatonin on telomerase activity in ageing of gastric mucosal tissues also is not known. In this study, we investigated the age-related changes in telomerase activity and cellular proliferation rate of gastric mucosa and the effect of melatonin. A total of 37 young (4 months old), and aged (20 months old) Wistar rats, kept under equal periods of light and dark, were divided into control [(PBS), i.p. for 21 days] and melatonin-treated (10 mg/kg melatonin, i.p. for 21 days) groups. Telomerase activity, cell proliferation rate, malondialdehyde (MDA) and glutathione (GSH) levels of the stomach were determined. Melatonin significantly inhibited the gastric mucosal proliferation rate of both young and aged rats. Telomerase activity was significantly reduced in aged rats compared to young animals. Melatonin significantly increased the telomerase activity of both young and aged rats. The MDA levels of gastric mucosa in the aged rats were significantly higher than those of the younger rats. On the contrary, the GSH levels of gastric mucosa of the aged group were significantly lower than that of the young rats. While melatonin had no effect on GSH levels of either young or aged rats, it significantly decreased the MDA levels in aged animals. In conclusion, melatonin may delay the ageing of gastric mucosa by inhibiting the replicative cellular senescence via its stimulatory effect on telomerase activity and suppressive effect on cellular proliferation and lipid peroxidation.
Tryptophan as a circulating precursor of serotonin (5-HT) may suppress food intake and body weight. Tryptophan administration can enhance the generation of reactive oxygen species (ROS) by inducing oxidative pathway in vivo and in vitro. We have examined the effect of repeated tryptophan administration on food consumption, body weight, brain lipid peroxidation and 5-HT immunoreactivity. Tryptophan was given at the dose of 100 mg/kg/24 hr in 0.2 ml saline solution i.p. for 7 days to mice. Control mice received 0.9% NaCL solution at the same manner and volume. Body weights were recorded at the beginning and end of the experiments. Thiobarbituric acid reactive substance (TBARS), the last product of lipid peroxidation, was measured spectrophotometrically. Brain 5-HT levels were determined by the immunohistochemical method. Our findings indicate that the tryptophan suppresses food intake significantly in mice. Body weight decreased and brain TBARS levels increased significantly by repeated tryptophan treatment. Immunohistochemical detection showed that 5-HT levels increased by tryptophan administration. There is a link between increased 5-HT level and oxidative stress by tryptophan administration on brain tissue. Tryptophan at repeated doses should be exercised carefully in clinical practice.
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