General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid.Report as inadecuate




General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 LNC - Lipides - Nutrition - Cancer U866 2 CHU Dijon

Abstract : To evaluate the effects of alpha-lipoic acid AL in a model of doxorubicin DOX-induced cardiotoxicity, male Wistar rats were treated with DOX 1 mg-kg-d; 10 d in combination or not with AL 50 mg-kg-d; 15 d. Plasma oxidative stress was determined by hydroperoxides ROOH and the ascorbyl radical-ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde MDA and O₂*⁻ dihydroethidium fluorescence content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX +16%, but this was due to ascites. Histological liver alterations were observed in both the DOX and DOX-AL groups. Plasma ROOH concentrations decreased after 10 days of AL treatment, but were greater in both the DOX and DOX-AL groups. After two months, a decrease in the cardiac contractility index -27% and -29%, respectively and cardiac hypertrophy were observed in DOX and DOX-AL. These dysfunctions were associated with 1 a reduction in plasma ascorbate levels and an increase in the ascorbyl-ascorbate ratio and 2 an increase MDA and O₂*⁻ content in cardiac tissue. In conclusion, a cumulative dose of 10 mg-kg doxorubicin induced functional alterations in the heart associated with plasma and cardiac oxidative stress. The co-administration of the antioxidant compound AL had no beneficial effects in this situation.





Author: Steliana Ghibu - Stéphanie Delemasure - Carole Richard - Jean-Claude Guilland - Laurent Martin - Ségolène Gambert - Luc Rochet

Source: https://hal.archives-ouvertes.fr/



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