No abstract

: Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several systems. The aim of this study was to investigate the role of melatonin against I/R injury of the rat urinary bladder. The abdominal aorta was clamped to induce ischemia for 30 min, then the animals were subjected to 60 min of reperfusion. Melatonin (10 mg/kg, i.p.) or the vehicle (control 1% alcohol i.p.) was administered before I/R. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for measurement of products of lipid peroxidation (LP), glutathione (GSH) levels and myeloperoxidase activity (MPO). Bladder strips were suspended in oxygenated Tyrode's buffer at 37°C and isometric contractions to carbachol (CCh; 10−8–10−4 m) were recorded. In the I/R group, the contractile responses of the bladder strips were lower than those of the control group (P < 0.01–0.001) and were reversed by treatment with melatonin (P < 0.05–0.001). LP which was higher in I/R group compared with control (27.68 ± 1.69 and 10.59 ± 1.27 nmol/g, respectively; P < 0.001) was partially reversed by melatonin (19.01 ± 1.85 nmol/g; P < 0.01). Similarly, GSH showed a decrease in the I/R group compared with controls (0.27 ± 0.03 and 0.43 ± 0.04 μmol/g, respectively; P < 0.05) and melatonin prevented this effect completely (0.45 ± 0.04 μ mol/g; P < 0.05). MPO activity in the I/R group (4.19 ± 0.08 U/g) was significantly higher than that of the control group (1.41 ± 0.08 U/g; P < 0.001) and melatonin treatment reduced MPO levels compared with I/R alone (3.16 ± 0.07; P < 0.001). Melatonin almost completely reversed the low contractile responses of rat urinary bladder strips to CCh and prevented oxidative tissue damage following I/R.

Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

In this study the corporeal tissues of rats exposed to ischemia-reperfusion had lower responses to contractile and relaxant agents than those of sham operated rats. Treatment with melatonin before ischemia-reperfusion almost completely reversed smooth muscle responses and prevented the increased myeloperoxidase activity and lipid peroxidation of corporeal tissues.

Alendronate causes serious gastrointestinal adverse effects. We aimed to investigate if free radicals have any role in the damage induced by alendronate and if melatonin or omeprazole is protective against this damage. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with melatonin or omeprazole. On the last day, following drug administration, pilor ligation was performed, and 2 hr later rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation, and myeloperoxidase and glutathione levels, as well as the histologic appearance of the stomach tissues, were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation and myeloperoxidase activity, while tissue glutathione levels decreased. Treatment with omeprazole or melatonin prevented this damage as well as the changes in biochemical parameters, and melatonin appeared to be more efficient than omeprazole in protecting the mucosa. Intraperitoneal administration of alendronate did not cause much gastric irritation. Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect and that melatonin and omeprazole are protective against this damage due to their antioxidant properties.