Abstract

Increases in tissue oxidative stress levels are associated with alterations in mitochondrial structure/function. We performed a study in 5 heart failure, type 2 diabetes patients where treatment (Tx) with (−)‐epicatechin (Epi) rich cocoa led to the recovery of skeletal muscle (SkM) mitochondrial cristae and increases in markers of biogenesis. In this study we evaluated SkM levels of indicators of tissue oxidative stress before and after 3 months of treatment with Epi‐rich cocoa containing ~100 mg of Epi. Biopsy SkM samples were assayed for changes in total thiols, nytrotyrosine and carbonylation levels and compared to values obtained from SkM of normal subjects. Prior to Tx, there were significant decreases in levels of SkM thiols and increases in nitrotyrosine and carbonylation levels which were restored by the use of Epi‐rich cocoa to levels similar to controls. To understand the mechanisms underlying these changes, a mouse model of diabetes was used (high fat diet; HFD). Similar changes were observed in SkM thiols, nitrotyrosine and carbonylation levels which were restored by Epi Tx for 2 weeks (1 mg/kg BID). SkM levels of molecular regulators of reactive oxygen species metabolism (superoxide dismutase and catalase) were decreased with HFD and restored by Epi. These results indicate that Epi can apparently reverse metabolic alterations in SkM REDUX status by exerting effects on key enzymatic control systems.

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