title: Protective effect of quercetin on chloroquine-induced oxidative stress and hepatotoxicity in mice.
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.
authors.affiliation: Genotoxicity Laboratory, Toxicology Division, CSIR-Central Drug Research Institute (CDRI), Lucknow 226 001, India.
authors.forename: Shrawan
authors.initials: S
authors.lastname: Kumar Mishra
authors.forename: Prabhat
authors.initials: P
authors.lastname: Singh
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath