The Effects of Chloroquine-Resistant and Chloroquine-Sensitive Strains of Berghei on Rodent Hepatic Drug-Metabolizing Enzymes
Uniformed Services University Of The Health Sciences Bethesda United States
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Malaria is one of the most important health problems in the world. The emergence and rapid spread of chloroquine resistance in malaria parasites is a major contributing factor to the failure of malaria control programs and to the diseases recent worldwide resurgence . The mechanisms for chloroquine resistance have not been fully elucidated, although several hypotheses have been proposed in the last 30 years. The present study determined the effect of infection with chloroquine-resistant RC strain or chloroquine-sensitive N strain P. berghei on cytochrome P450-dependent enzyme activities, growth rate, and virulence. Mean patent period of infection with the N strain was 7.28 days, and with the RC strain was 18.67 days. Mortality caused by the N strain was 100 and that by the RC strain only 2.50. The chloroquine-resistant parasites grew more slowly and were less virulent than the chloroquine-sensitive parasites. Infection with the N strain decreased total hepatic cytochrome P450 content and benzoapyrene hydroxylase activity of the uninfected controls by 37 and 40, respectively P0.01. There were no significant differences in these measures between mice infected with the RC strain and uninfected mice. In contrast, infection with the RC strain increased total activity of benzphetamine N-demethylase by 83 over infection with the N strain and by 68 over uninfected controls P0.01. However, there was no significant difference in the N-demethylase activity between livers of mice infected with the N strain and uninfected mice.