An Insight into the Current Perspective and Potential Drug Targets for Visceral Leishmaniasis (VL)

Leishmaniasis is one of the six entities on the list of most important diseases of the World Health Organization/Tropical Disease Research (WHO/TDR). After Malaria, it is one of the most prevalent and lethal parasitic diseases. VL is the fatal form of this disease, especially if left untreated. The drugs that are currently available for the treatment of VL are expensive, toxic, or no longer effective, especially in endemic regions. Currently, no vaccine has been developed to immunize humans against VL. The major problems with the current drugs are the development of resistance and their adverse effects. Therefore, there is a strong urge to research and design drugs that have better efficacies and low toxicities as compared to current chemotherapeutic drugs. Leishmania has various enzymes involved in its metabolic pathways, which are unique to either the same genus or trypanosomatids, making them a very suitable, attractive and novel target sites for drug development. One of the significant pathways unique to trypanosomatids is the thiol metabolism pathway, which is involved in the maintenance of redox homeostasis as well as protection of the parasite in the macrophage from oxidative stress-induced damage. In this review the several pathways, their essential enzymes as well as the proposed changes in the parasites due to drug resistance have been discussed to help to understand the most suitable drug target. The thiol metabolism pathway is discussed in detail, providing evidence of this pathway being the most favorable choice for drug targeting in VL.

Modulation of ascorbate-glutathione cycle by selenate and sulphate treatments in the seedlings of two rice (Oryza sativa L.) cultivars

The trace element Selenium (Se) has a dual role in the growth and metabolism of plants. Low concentration of selenium (2 ?M selenate) promotes growth and counteracts the detrimental effects of abiotic stress as opposed to higher levels (?10 ?M) where it acts as a pro-oxidant. We focused on both individual and interactive influence of selenate and sulphate on thiol metabolism in seedlings of rice cultivars, satabdi and khitish. Inhibition of ascorbate contents by about 17% on an average, in the test seedlings treated with Se correlated with increased activities of ascorbate peroxidase and ascorbate oxidase in the cultivars. The glutathione levels also increased significantly, on an average by about 102% in roots and 74% in shoots of cv. satabdi compared to a rise, by about 49% in roots and 56% in shoots of cv. khitish. The elevated level of glutathione coincided with the stimulatory influence of Se on its regulatory enzymes. Concomitantly the levels of ?-tocopherol and phytochelatins were also induced in both the test cultivars. Increase in ?-tocopherol activity reached a maximum by about 47% in roots and 80% in shoots of cv. satabdi whereas it increased by about 36% in roots and about 64% in shoots of cv. khitish. Substantive increase in the levels of PC4 followed by PC2 and PC3 was also noted. The effects were found to be less conspicuous in shoots than in roots. Rice seedlings exposed to combined Se and 10mM sulphate treatments showed improved growth and development as a result of better thiol metabolism due to amelioration of the adverse effects caused by selenium alone on all the parameters tested.