calpain and Hyperlipidemias

Lung fibrosis is a common side effect of the chemotherapeutic agent bleomycin and current evidence suggests that reactive oxygen species play a key role in the development of lung injury. We examined whether grape seed and skin extract (GSSE), a polyphenolic mixture exhibiting antioxidant properties, is able to protect against bleomycin-induced lung oxidative stress and injury.. Rats were pre-treated during three weeks either with vehicle (ethanol 10% control) or GSSE (4g/kg), then administered with a single high dose bleomycin (15mg/kg) at the 7th day.. Bleomycin increased lung lipoperoxidation, carbonylation and decreased antioxidant enzyme activities as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Bleomycin also induced copper depletion from the lung and iron accumulation within the lung, but had no effect on either zinc nor manganese. Correlatively bleomycin decreased the copper associated enzyme tyrosinase, increased the zinc dependent lactate dehydrogenase (LDH) and did not affect the manganese dependent glutamine synthetase. GSSE efficiently counteracted almost all bleomycin-induced oxidative stress, biochemical and morphological changes of lung tissue.. Data suggest that GSSE exerts potent antioxidant properties that could find potential application in the protection against bleomycin-induced lung fibrosis.

Topics: Animals; Antioxidants; Bleomycin; Body Weight; Calpain; Chromatography, Liquid; Grape Seed Extract; Hyperlipidemias; Intracellular Space; Lipid Peroxidation; Lung; Male; Metals; Organ Size; Oxidative Stress; Protective Agents; Protein Carbonylation; Rats, Wistar; Tandem Mass Spectrometry

Hyperlipidemia is a highly prevalent risk factor for ischemic stroke. Its impact on brain injury and blood-brain barrier permeability, so far, has not been assessed in animal models of ischemic stroke.. Wild-type and apolipoprotein E(-/-) mice, fed with normal or cholesterol-rich high-fat food, were subjected to 30 minutes of middle cerebral artery occlusion. Ischemic injury, brain edema, IgG extravasation, lipid peroxidation, calpain-1/2, matrix metalloproteinase-2/9, and RhoA activation, and occludin expression were evaluated 24 hours after reperfusion.. Cholesterol-rich food, but not apolipoprotein E deficiency, increased IgG extravasation and brain edema without influencing infarct area and the density of DNA fragmented cells. Increased lipid peroxidation and low-density lipoprotein oxidation were noticed in the brain of hyperlipidemic mice and were associated with increased activation of calpain-1/2 and matrix metalloproteinase-2/9, overactivation of RhoA and its guanine exchange factor leukemia-associated guanine exchange factor , and downregulation of the tight junction protein occludin in cerebral microvessels.. That postischemic blood-brain barrier permeability and brain edema are increased during hyperlipidemia points toward the importance of the recognition and adequate treatment of this highly prevalent condition. Translational studies should more adequately mimic risk factors prevalent in human stroke.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Calpain; Capillary Permeability; Enzyme Activation; Hyperlipidemias; Lipid Peroxidation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Knockout; rho GTP-Binding Proteins; rhoA GTP-Binding Protein