Abstract
The present study was aimed to find out the protective effect of quercetin on hepatotoxicity resulting by commonly used antimalarial drug chloroquine (CQ). Swiss albino mice were administered with different amounts of CQ ranging from human therapeutic equivalent of 360 mg/kg body wt. to as high as 2000 mg/kg body wt. We observed statistically significant generation of reactive oxygen species, liver toxicity, and oxidative stress. Our observation of alterations in biochemical parameters was strongly supported by real-time PCR measurement of mRNA expression of key biochemical enzymes involved in hepatic toxicity and oxidative stress. However, the observed hepatotoxicity and accompanying oxidative stress following CQ administration show dose specific pattern with little or apparently no effect at therapeutic dose while having severe effects at higher dosages. We further tested quercetin, an antioxidant flavanoid, against CQ-induced hepatoxicity and found encouraging results as quercetin was able to drastically reduce the oxidative stress and hepatotoxicity resulting at higher dosages of CQ administration. In conclusion, our study strongly suggests co administration of antioxidant flavonoid like quercetin along with CQ for antimalarial therapy. This is particularly important when CQ is administered as long-term prophylactic treatment for malaria as chronic exposure has shown to be resulting in higher dose level of drug in the body.
Highlights
Chloroquine [7-chloro-4-(4-diethylamino-1-methylbutylamino) quinoline, CQ] is a 4-aminoquinoline derivative antimalarial compound
Peripheral blood mononuclear cells isolated from different groups of animals were labeled with H2DCFDA, and increase in mean fluorescence intensity was analyzed by flow cytometry
An approximate 3.45 fold increase of the oxidized DCF mean peak, indicative of higher H2O2 content, was observed in Group 4 animals treated with 2000 mg/Kg of chloroquine compared with untreated control of Group 1 animals
Summary
Chloroquine [7-chloro-4-(4-diethylamino-1-methylbutylamino) quinoline, CQ] is a 4-aminoquinoline derivative antimalarial compound. Liver being the largest gland and major site for drug metabolism has aroused considerable interest among researchers, and some studies were conducted in the past that have addressed the chloroquine-induced hepatotoxicity [13, 14]. There have been few other reports [16, 17] that consider malaria infection as such a cause for oxidative stress and propose antioxidant action of CQ for its antimalarial property. In contrast to previous two distinct convictions, there are reports [18, 19] that say that CQ has little or no role in oxidative stress in malaria-infected or healthy animals. Quercetin has been applied for clinical therapy because of its multiple pharmacological activities, such as suppression of cell proliferation, protection of LDL oxidation, prevention
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