Leishmaniasis: current status of available drugs and new potential drug targets

The control of Leishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericin B, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

In vivo antioxidant and hepatoprotective activity of methanolic extracts of Daucus carota seeds in experimental animals

Objective: To assess the In vivo antioxidFant and hepatoprotective activity of methanolic extract of Daucus carota (D. carota) seeds in experimental animals. Methods: Methanolic extracts of D. carota seeds is used for hepatoprotection assessment. Oxidative stress were induced in rats by thioacetamide 100 mg/kg s.c, in four groups of rats (two test, standard and toxic control). Two test groups received D. carota seeds extract (DCSE) at doses of 200 mg/kg and 400 mg/kg. Standard group received silymarin (25 mg/kg) and toxic control received only thioacetamide. Control group received only vehicle. On the 8th day animals were sacrificed and liver enzyme like serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) were estimated in blood serum and antioxidant enzyme like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and lipid peroxidation (LPO) were estimated in liver homogenate. Results: A significant decrease in SGPT, SGOT and ALP levels was observed in all drug treated groups as compared to thioacetamide group (P < 0.001) and in case of antioxidant enzyme a significant (P < 0.001) increase in SOD, CAT, GRD, GPX and GST was observed in all drug treated groups as compared with thioacetamide group. But in case of LPO a significant (P< 0.001) reduction was observed as compared to toxic control group. Conclusions: DCSE has contributed to the reduction of oxidative stress and the protection of liver in experimental rats.