To study the effects of APE on myocardial mitochondrial bioenergetics, Type I diabetes mellitus was induced in male Sprague Dawley rats by a single streptozotocin (STZ) injection (60 mg/kg.bw; i.p). After 3 weeks rats were orally treated (every third day) with distilled water (3ml/kg.bw) or APE (30 mg/kg. bw) for 5 weeks. The vehicle group was given citrate buffer followed by APE treatment. Heart mitochondrial functional parameters were measured using a Clark‐type oxygen electrode and employing a combination of malate (M), palmitoyl‐L‐carnitine (CP), pyruvate (P) and succinate as oxidative substrates. ADP/O ratio was increased in the diabetic group in the presence of MCP and M+P. APE treatment reduced ADP/O ratio and rate of ADP phosphorylation (MCP and succinate as substrates). Treatment of the diabetic group with APE attenuated the ADP/O ratio (for all substrates used) and decreased ADP phosphorylation rate (MCP as substrates), while it increased oligomycin‐insensitive proton leak and state 4 respiration (succinate as substrate). Our results demonstrate that APE inhibits rat heart mitochondrial efficiency and uncouples oxidative phosphorylation in a substrate‐dependent fashion and may help explain observed cardiac dysfunction associated with usage of this medicinal plant. South African Medical Research Council, South African National Research Foundation.
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