Cystatin C has a dual role in post-traumatic brain injury recovery.

Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles) increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles) decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury.

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia-reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI-associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre-ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event-caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.

Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity.

Adrenal chromaffin cell (ACC) transplants, alone or combined with levodopa treatment, were used in attempted therapy for Parkinson's disease (PD). In a previous study, we demonstrated that levodopa caused chromaffin cell death either by necrosis or by apoptosis in cell culture. Here we report the beneficial effect of a water-soluble derivative of fullerene C(60) (a novel molecule with potent antioxidant properties) and of ascorbic acid when applied to chromaffin cell cultures exposed to levodopa. Both antioxidants remarkably increase the ACC survival and prevent cell death, including apoptosis. Although ACC transplants are not currently considered as an option for PD treatment, these observations should help in exploring the possibilities of preventing the neurotoxicity generated by levodopa and in envisaging new strategies for PD treatment by combining the clinical use of levodopa and potent antioxidants. Chemical properties of fullerene related to biological uses are discussed.