Acute renal failure is a major complication of gentamicin (GEN), which is widely used in the treatment of gram-negative infections. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites (or free radicals) are important mediators of gentamicin nephrotoxicity. In this study we investigated the role of free radicals in gentamicin-induced nephrotoxicity and whether melatonin, a potent antioxidant could prevent it. For this purpose female Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40 mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control) twice daily for 14 days. The rats were decapitated on the 15th day and kidneys were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal tissue. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of BUN and creatinine levels. The significant decrease in GSH and increases in MDA levels, PO and MPO activity indicated that GEN-induced tissue injury was mediated through oxidative reactions. On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment.

Agmatine, an endogenous cationic amine, exerts a wide range of biologic effects, but its physiologic role is still to be determined. The aim of the present experiments was to investigate the role of agmatine in anxiety and depression. The forced swim test (FST) and the elevated plus maze (EPM) were used to determine the antidepressant and anxiolytic effects of agmatine in comparison with imipramine (30 mg/kg i.p.). Agmatine (10, 20, 40, 80, or 100 mg/kg, i.p.), saline, or imipramine was given 30 minutes before the tests. Agmatine decreased immobility time in the FST and increased the time spent in the open arms in the EPM, as compared with the saline group. As an endogenous substance, agmatine have modulatory effect on anxiety and depression.

In order to investigate the possible relationship between atherosclerosis and chronic Pseudomonas aeruginosa infection, 66 Wistar rats were given five separate intratracheal inoculations of either P. aeruginosa or sterile saline at 4-week intervals. The rats were divided into four groups: group 1 was infected with P. aeruginosa and fed a diet containing cholesterol 1% w/v; group 2 was infected with P. aeruginosa and fed a normal diet; group 3 was not infected and was fed a diet containing cholesterol 1% w/v; and group 4 (the control group) was not infected and was fed a normal diet. One month after the final inoculation, the rats were killed humanely; computerised image analysis was used to evaluate sections of the aorta and heart, and the maximal wall thickness of the aorta and coronary artery. The aortic wall thickness was significantly greater for group 1 (329.53 +/- 58.06 microm) compared to groups 2 (190.59 +/- 27.81 microm; p < 0.0001), 3 (262.90 +/- 61.12 microm; p < 0.0004) and 4 (158.00 +/- 30.30 microm; p < 0.0001). Similarly, the coronary artery wall thickness was significantly greater for group 1 (72.96 +/- 10.67 microm) compared to groups 2 (35.07 +/- 8.53 microm; p < 0.0001), 3 (41.45 +/- 10.22 microm; p < 0.0001) and 4 (32.30 +/- 5.27 microm; p < 0.0001). These findings strengthen the hypothesis that chronic infection plays a role in the pathogenesis of atherosclerosis.

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