Induction and uncoupling of rat liver mitochondria by oral administered coartemether

Induction and uncoupling of rat liver mitochondria by oral administered coartemether

Author by Dr. Godswill Anyasor

Journal/Publisher: American Journal Of Biochemistry And Molecular Biology

Volume/Edition: 3

Language: English

Pages: 110 - 118

Abstract

This study investigated the cytotoxic effect of varying doses of antimalarial coartemether (2.0, 4.0, 8.0 and 10.0 mg kg-1) in the presence of ferrous sulphate (2800 mg kg-1) for 3 days on normal rat liver mitochondrial membrane permeability transition pore opening and F1F0 ATPase activity. Swelling was estimated spectrophotometrically under succinate energized condition. Calcium ion treated mitochondria preloaded with coartemether induced swelling in a concentration dependent manner in vitro. Swelling was amplified in the presence of ferrous. Coartemether alone and combined coartemether-ferrous also induced mitochondrial swelling in the presence of spermine. In vivo study further showed that 10.0 mg kg-1 coartemether induced swelling in the presence of ferrous. Coartemether stimulated an increased activity of mitochondrial F1F0 ATPase in a concentration dependent manner. Thus, these findings indicate that coartemether at high dose in the presence of ferrous sulphate could be an inducer of mitochondrial mega pore opening and an uncoupler of oxidative phosphorylation initiating apoptosis.


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