%0 Journal Article
%T Protective Effect of Quercetin on Chloroquine-Induced Oxidative Stress and Hepatotoxicity in Mice
%A Shrawan Kumar Mishra
%A Prabhat Singh
%A Srikanta Kumar Rath
%J Malaria Research and Treatment
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/141734
%X 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. 1. Introduction Chloroquine [7-chloro-4-(4-diethylamino-1-methylbutylamino) quinoline, CQ] is a 4-aminoquinoline derivative antimalarial compound. Apart from being an established antimalarial, CQ also finds use as an anti-inflammatory drug in the treatment of rheumatoid arthritis [1¨C3], discoid lupus erythematosus [4, 5], and amoebic hepatitis [6]. In spite of reports of chloroquine resistance in many parts of the world, it is still used as first line of therapy against malaria in many developing countries owing to its being readily available and cheaper. However, despite being effective in range of diseases, its use was always under scrutiny as it has narrow safety margin and has shown wide range of side effects including cardiac and neurological disorders, retinopathy, and ototoxicity [7¨C9]. Severe liver injury and hepatitis in the presence or absence of systemic features have also been described in CQ users [10¨C12]. 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
%U http://www.hindawi.com/journals/mrt/2013/141734/