Ameliorative effect of curcumin on hepatotoxicity induced by chloroquine phosphate.
ABSTRACT India is one of the most endemic areas, where malaria predominates and its control has become a formidable task. Chloroquine phosphate (CQ) on account of its rapid action on blood schizontocide of all the malarial parasite strains has become the most widely prescribed drug for prophylaxis and treatment of malaria. Toxicity of CQ is most commonly encountered at therapeutic and higher doses of treatment. Thus, the present study was undertaken to evaluate the protective effect of Curcumin, a herbal antioxidant obtained from Curcuma longa, on hepatic biochemical and histopathological status of CQ induced male mice. Swiss albino male mice were administered oral doses of CQ (100mg/kg body wt., 200mg/kg body wt. and 300mg/kg body wt.) and CQ+curcumin (300mg/kg body wt.+80mg/kg body wt.) for 45 days. A withdrawal of high dose treatment for 45 days was also studied. Administration of CQ brought about a significant decrease in Protein content with a decline in SDH, ATPase and ALKase activities, whereas ACPase activity was found to be significantly increased following CQ treatment. Antioxidant enzyme SOD registered a significant reduction as opposed to TBARS which was found to be elevated in a significant manner in the CQ treated groups as compared to control. Gravimetric indices (body weight and organ weight) declined significantly following CQ treatment. Administration of curcumin exhibited significant reversal of CQ induced toxicity in hepatic tissue. Protein content, SDH, ATPase, ALKase, ACPase, SOD, TBARS, body weight and organ weight were found to be comparable to that of control group after curcumin administration. Thus, obtained results led us to conclude the curative potential of curcumin against CQ induced hepatotoxicity.
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ABSTRACT: Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets.Journal of Biological Chemistry 07/2012; 287(40):33198-214. · 4.65 Impact Factor
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ABSTRACT: Occupational or environmental exposures to heavy metals produce several adverse health effects. The common mechanism determining their toxicity and carcinogenicity is the generation of oxidative stress that leads to hepatic damage. In addition, oxidative stress induced by metal exposure leads to the activation of the nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH-associated protein 1/antioxidant response elements (Nrf2/Keap1/ARE) pathway. Since antioxidant and chelating agents are generally used for the treatment of heavy metals poisoning, this review is focused on the protective role of curcumin against heavy metals liver injury. Curcumin has shown, in clinical and preclinical studies, numerous biological activities including therapeutic efficacy against various human diseases and anti-hepatotoxic effects against environmental or occupational toxins. Curcumin reduces the hepatotoxicity induced by arsenic, cadmium, chromium, copper, lead and mercury, prevents histological injury, lipid peroxidation and glutathione (GSH) depletion, maintains the liver antioxidant enzyme status and protects against mitochondrial dysfunction. The preventive effect of curcumin on the noxious effects induced by heavy metals has been attributed to its scavenging and chelating properties, and/or to the ability to induce the Nrf2/Keap1/ARE pathway. However, additional research is needed in order to propose curcumin as a potential protective agent against liver damage induced by heavy metals.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2014; · 2.99 Impact Factor
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ABSTRACT: To evaluate the alleviating effects of melatonin on oxidative changes in the testes and pituitary gland induced by subacute chlopyrifos (CPF) exposure in rats. Forty adult male Wistar rats divided into 4 groups of 10 animals were used for the study. Group I received soya oil (2 mL/kg) while group II was administered with melatonin (0.5 mg/kg). Group III was administered CPF only (8.5 mg/kg ∼ 1/10th of the LD50) while group IV was pretreated with melatonin (0.5 mg/kg) and then exposed to CPF (8.5 mg/kg), 10 min later. The regimens were administered by gavage once daily for a period of 28 d. At the end of the exposure period, the rats were sacrificed and the testicular tissues and pituitary glands were evaluated for the malonaldehyde (MDA) concentration and activities of superoxide dismutase (SOD) and catalase (CAT). CPF increased MDA concentrations and reduced the activities of SOD and CAT in the testes and pituitary gland. Melatonin pretreatment reduced the testicular and pituitary MDA concentrations and improves the SOD and CAT activities. the study showed that subacute CPF-induced oxidative stress in the testes and pituitary glands were alleviated by melatonin due to its antioxidant property.Asian Pacific Journal of Tropical Biomedicine 08/2012; 2(8):645-50.