In the present study, we investigated whether erythropoietin (Epo) has a protective effect against cytotoxicity induced by interferon-gamma (IFN-
γ) and lipopolysaccharide (LPS) in primary rat oligodendrocyte cultures. The possible modulatory effect of erythropoietin on inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production were also analyzed. Erythropoietin exerted a significant protective effect against IFN-γ and LPS-induced oligodendrocyte injury as determined by lactate dehydrogenase assay. Treatment with erythropoietin inhibited the expression of iNOS mRNA and nitrite production resulting from proinflammatory stimulation by IFN-γ and LPS. These results suggest that erythropoietin has protective effects against inflammatory oligodendrocyte injury in vitro and may play a protective role in neurological disorders characterized by oligodendrocyte death, such as multiple sclerosis.
The present study evaluated the impact of neonatal administration of capsaicin (neurotoxin from red hot pepper used for sensory denervation) on postnatal development of the heart rate and ventricular contractility. In the rats subjected to capsaicin administration (100mg/kg) on postnatal days 2 and 3 and their vehicle-treated controls at the ages of 10 to 90
days, function of the sympathetic innervation of the developing heart
was characterized by evaluation of chronotropic responses to
metipranolol and atropine, norepinephrine concentrations in the heart, and norepinephrine release from the heart atria. Sensory denervation was verified by determination of calcitonin gene-related peptide levels in the heart. Direct cytotoxic effects of capsaicin were assessed on cultured neonatal cardiomyocytes. Capsaicin-treated rats displayed higher resting heart rates, lower atropine effect, but no difference in the effect of metipranolol. Norepinephrine tissue levels and release did not differ from controls. Contraction force of the right ventricular papillary
muscle was lower till the age of 60 days. Significantly reduced viability of neonatal cardiomyocytes was demonstrated at capsaicin concentration 100 μmol/l. Our study suggests that neonatal capsaicin treatment leads to impaired maturation of the developing cardiomyocytes. This effect cannot be attributed exclusively to sensory denervation of the rat heart since capsaicin acts also directly on the cardiac cells.