Enalapril treatment discloses an early role of angiotensin II in inflammation- and oxidative stress-related muscle damage in dystrophic mdx mice

Publication date: November 2011 Source:Pharmacological Research, Volume 64, Issue 5 Author(s): Anna Cozzoli , Beatrice Nico , Valeriana Teresa Sblendorio , Roberta Francesca Capogrosso , Maria Maddalena Dinardo , Vito Longo , Sara Gagliardi , Monica Montagnani , Annamaria De Luca Inhibitors of angiotensin converting enzymes (ACE) are clinically used to control cardiomyopathy in patients of Duchenne muscular dystrophy. Various evidences suggest potential usefulness of long-term treatment with ACE inhibitors to reduce advanced fibrosis of dystrophic muscle in the mdx mouse model. However, angiotensin II is known to exert pro-inflammatory and pro-oxidative actions that might contribute to early events of dystrophic muscle degeneration. The present study has been aimed at evaluating the effects of an early treatment with enalapril on the pathology signs of exercised mdx mouse model. The effects of 1 and 5mg/kg enalapril i.p. for 4–8 weeks have been compared with those of 1mg/kg α-methyl-prednisolone (PDN), as positive control. Enalapril caused a dose-dependent increase in fore limb strength, the highest dose leading to a recovery score similar to that observed with PDN. A dose-dependent reduction of superoxide anion production was observed by dihydroethidium staining in tibialis anterior muscle of enalapril-treated mice, approaching the effect observed with PND. In parallel, a significant reduction of the activated form of the pro-inflammatory Nuclear Factor-kB ha...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research