Gianluigi Vendemiale

Background The reason why some hepatitis C virus carriers with normal aminotransferase activity present, during time, an activation of the disease, is unknown. The aim of this study was to assess th...

Oxidative damage to lens proteins is a major factor leading to cataract formation. It is of pathogenic importance to determine a threshold of protein oxidation over which opacification of the lens takes place. Sixty-two lenses extracted from patients affected by idiopathic senile, diabetic, or myopic cataract were studied. Clear lenses were obtained from subjects undergoing enucleation (n = 10) or vitrectomy for giant retinal tears (n = 9), and were age- and sex-matched to those with cataract. The content of carbonyls and sulfhydryls (P-SH) in proteins in the lens was assessed using spectrophotometric assay. An age-associated inverse relation (P < 0.01) was noted in the content of P-SH, the concentrations of which were also inversely related (P < 0.03) to the content of protein carbonyls. These changes were more pronounced in cataracts than in clear lenses and in diabetic and myopic cataracts when compared with senile cataracts. The drop of P-SH concentration occurred earlier in diabetic and in myopic cataracts than in senile cataracts. The accumulation of protein carbonyls > 2 nmol/mg protein and the decrease of P-SH below 12 to 10 nmol/mg protein were always accompanied by lens opacification. Idiopathic senile, diabetic, and myopic cataractogenesis appear to be dependent on oxidative damage to lens proteins. This damage occurs earlier in myopic and diabetic patients. Values of P-SH below and protein carbonyls above their specific threshold were found to be predictive for the presence of cataract. Because increased oxidation was observed in clear lenses removed from myopic and diabetic subjects, oxidation may be involved in the pathogenesis of these forms of human cataract.

This study investigated the dose- and time-dependent effect of ethanol on gastric and intestinal glutathione and protein oxidative state in the rat. Rats received 1 or 4 g/kg of 25% ethanol solution orally or isocaloric glucose. Some rats received diethylmaleate, cimetidine or cyanamide before ethanol (1 g/kg). Glutathione, carbonyl proteins and histological damage were evaluated in the gastric and intestinal mucosa 6 hours after treatment. An increase in glutathione was observed 2 to 6 hours after 1 g/kg of ethanol both in the gastric and intestinal mucosa, whereas 4 g/kg decreased glutathione. The rise in glutathione after ethanol was associated with increased levels of its oxidized form; however, the total/oxidized ratio was significantly decreased only in the intestinal tract. Diethylmaleate depleted mucosal glutathione, while the subsequent ingestion of ethanol increased it. Unlike stomach, intestine showed a significant increase in carbonyl proteins and marked histological lesions after ethanol ingestion. Cimetidine and cyanamide inhibited by 50% the activity of alcohol dehydrogenase and by 80% aldehyde dehydrogenase, respectively, in the gastric and intestinal mucosa. Cyanamide significantly enhanced ethanol-induced protein oxidation and mucosal injury in the stomach. No such effect was observed in the intestine. The increase of glutathione after ingestion of low amounts of ethanol appears to be an adaptive mechanism against ethanol toxicity. Depletion of glutathione increased protein oxidation and the extent of histological damage in ethanol-treated rats. At gastric level, the effects of ethanol are exaggerated by the inhibition of acetaldehyde metabolism; while intestinal damages appear to be ascribed to ethanol itself.