The inhibition of succinate oxidation in both heart and liver mitochondria by the cardiotoxic anticancer antibiotic adriamycin in vitro was reversed to a large extent by exogenous ubiquinone-45. Inhibition of the oxidation of NAD+-linked substrates in heart and liver mitochondria responded differently to ubiquinone, the inhibition being reversed only in liver organelles. Administration of adriamycin inhibited oxidative phosphorylation in rat heart, kidney and liver mitochondria, the inhibition being highest in the heart organelles (about 50% for both NAD+-linked substrates and succinate). Exogenous addition of ubiquinone to mitochondria isolated from drug-treated animals did not reverse the inhibition. Administration of ubiquinone along with adriamycin did not change effectively the pattern of drug-mediated decrease in oxidative activity of the organelles, particularly in the heart.
Extracts from leaves and stem bark of Piper guineense were evaluated for trypanocidal activity against Trypanosoma brucei brucei in vitro and in vivo. The phytochemical screening of the most active extracts in vitro was carried out. The Petroleum ether extract of stem bark exhibited highest in vitro trypanocidal activity out of the six extracts tested. Thus it was used to treat animals infected with Trypanosoma brucei brucei at a dose range of 50-200 mg/kg body weight, intraperitoneally and orally. The results showed that the group treated with 100 mg/kg body weight intraperitoneally showed significant reduction in parasiteamia with a prolonged life span up to the 18th day post infection. While those that were treated with 200 mg/kg body weight orally, had progressive increase in parasiteamia up to the 7th and 8th day post infection when they all died. However in the prophylactic experiment animals that were treated with 50 mg/kg intraperitoneally and 100 mg/kg orally for five days before challenging them with 10 3 trypanosomes, did not develop parasiteamia up to 28th day post infection when the experiment was terminated. This experiment shows that the petroleum ether of Piper guineense possesses some degree of trypanocidal activity and further purification of the active component should be carried out.
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