TEMPOL, a membrane-permeable radical scavenger, ameliorates lipopolysaccharide-induced acute lung injury in mice: a key role for superoxide anion

Acute lung injury [ALl] or acute respiratory distress syndrome is a serious clinical problem with high mortality. Oxidative stress was found to play a major role in mediating lung injury and antioxidants have been shown to be effective in attenuating ALI. In this study, we determine the effects of tempol, a membrane-permeable radical scavenger, in lipopolysaccharide [LPS] induced ALl and the underlying mechanism. ALl was induced by intraperitoneal injection of LPS [lmglkg] and mice were treated with tempol 30 mm before injection of LPS. One hour later, bronchoalveolar lavage fluid [BALF] was collected and subjected to estimation of total and differential cell counts as svell as the proinflammatory cytokines; tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta [IL-1beta] and interferon-gamma [IFN-gamma]. Lung tissue damage was confirmed by histopathological changes and by immunohistochemical analysis of myeloperoxidase [MPO]. Moreover, lipid peroxidation, reduced glutathione [GSH] and nitric oxide [NO] were investigated in the lung tissue. Pretreatment with tempol produced significant attenuation of LPS-induced lung injury as well as inhibition of LPS mediated increase in MPO immunostaining, MDA and NO levels in lung tissue. Elevated cytokines levels in both BALF and lung tissue homogenates of ALl mice were significantly decreased after administration of tempol. These findings confirmed significant protection by tempol against LPS-induced acute lung injury and that superoxide anion scavenging appears to be a potential target for new potential therapy in pulmonary disorders

Effect of coenzyme Q - 10 and alpha - tocopherol on the hepatotoxicity induced by carbon tetrachloride

This work aimed to compare the in vivo protective effect of coenzyme Q- 10 and vitamin E against the hepatotoxicity induced by carbon tetrachloride in rats. Pretreatment was carried out for 14 days with either coenzyme Q-10 or vitamin E before CC14 was administrated. Serum AST, ALT and ALP were measured as well as liver LDH, cytochrome oxidase, MDA, GSH and GSH-Px. It was shown that CC14 administration induced many toxic effects on liver functions which was apparent from the increased serum AST, ALT and ALP activities; the severe increase in LDH activity and MDA level; the reduction of cytochrome oxidase and GSHPx activities and the depletion of GSH in liver tissue of CCl4-administered rats. Pretreatment with coenzyme Q-10 or vitamin E succeeded to protect the liver from the hepatotoxic effect of CC14. This was evident from the normalized serum ALT and ALP activities; the decrease in MDA content; LDH and cytochrome oxidase activities and the increased value of GSH and GSH-Px activity in liver tissue of rats pretreated with either coenzyme Q-10 or vitamin-E. This study proved that coenzyme Q-10 showed similar protective effect to vitamin E as a potent antioxidant and could be suggested as a hepatoprotective agent

Contribution of nitric oxide, monoaminergic and opioidergic systems to the antinociceptive effects of tramadol and clonidine in rats and mice

In this study, thermal and chemical stimuli using hot plate and acetic acid tests were used. Tramadol hydrochloride produced antinociception in both hot plate test in rats and acetic acid analysis in mouse. The antinociceptive activity of tramadol was abolished by naloxone. Administration of yohimbine also reduced antinociception produced by administration of tramadol. These results suggested that tramadol- induced antinociception might be mediated by opioid and non-opioid mechanisms. Clonidine produced dose dependent antinociception using hot plate test. It was concluded that opioid receptors, alpha 2-adrenergic receptors and nitric oxide might play a role in pain transmission