Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma

Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On the 9(th) day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and hepatic antioxidative parameters. The rest were kept for assessment of survival parameters. TDA exhibited dose dependent and significant increase in tumor weight, tumor volume, packed cell volume and viable cells and reduced non-viable cells and life span of EAC bearing animals. Hematological parameters were significantly worsened in TDA-treated mice. TDA treatment significantly aggravated the hepatic antioxidative parameters. The present study demonstrated that T. dioica root possessed tumor promoting activity in EAC bearing albino mice, plausibly mediated by attenuation of endogenous antioxidant systems.     

Novel antimalarial drug targets: hope for new antimalarial drugs

Malaria is a major global threat, that results in more than 2 million deaths each year. The treatment of malaria is becoming extremely difficult due to the emergence of drug-resistant parasites, the absence of an effective vaccine, and the spread of insecticide-resistant vectors. Thus, malarial therapy needs new chemotherapeutic approaches leading to the search for new drug targets. Here, we discuss different approaches to identifying novel antimalarial drug targets. We have also given due attention to the existing validated targets with a view to develop novel, rationally designed lead molecules. Some of the important parasite proteins are claimed to be the targets; however, further in vitro or in vivo structure-function studies of such proteins are crucial to validate these proteins as suitable targets. The interactome analysis among apicoplast, mitochondrion and genomic DNA will also be useful in identifying vital pathways or proteins regulating critical pathways for parasite growth and survival, and could be attractive targets. Molecules responsible for parasite invasion to host erythrocytes and ion channels of infected erythrocytes, essential for intra-erythrocyte survival and stage progression of parasites are also becoming attractive targets. This review will discuss and highlight the current understanding regarding the potential antimalarial drug targets, which could be utilized to develop novel antimalarials.     

Antiplasmodial activity of [(aryl)arylsulfanylmethyl]Pyridine

A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H(2)O(2), and hydroxyl radical (.OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (DeltaPsim) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of .OH may be mainly responsible for the antimalarial effect of AASMP since .OH scavengers such as mannitol, as well as spin trap alpha-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.     

Sporotrichosis in north-east India

Reports on the occurrence of sporotrichosis in some parts of north-east India are scarce. We report here five cases of lymphocutaneous sporotrichosis from north-east India, including one from Sikkim State and four from distant places in the north-eastern part of West Bengal. All patients were full or part-time farmers or gardeners. Diagnosis of sporotrichosis was confirmed by isolation of Sporothrix schenckii in culture and in vitro conversion of the isolates to yeast form. The cases were treated with 50% solution of potassium iodide.     

Toxicity of the quinalphos metabolite 2-hydroxyquinoxaline: growth inhibition, induction of oxidative stress, and genotoxicity in test organisms

The quinalphos metabolite 2-hydroxyquinoxaline (HQO), previously shown to photocatalytically destroy antioxidant vitamins and biogenic amines in vitro, was tested for toxicity in several small aquatic organisms and for mutagenicity in Salmonella typhimurium. In the rotifer Philodina acuticornis, HQO caused the disappearance of large individuals and increased hydroperoxide concentration. The latter effect was not only observed in animals kept in a light/dark cycle, but also in constant darkness, indicating that HQO can assume a reactive state and/or form reactive intermediates under the influence of either light or redox-active metabolites, in particular, free radicals. Cell proliferation was inhibited in the ciliate Paramecium bursaria. In the dinoflagellate Lingulodinium polyedrum, which allows early detection of cellular stress on the basis of bioluminescence measurements, strong rises in light emission became apparent on the 2nd day of exposure to HQO and continued until cells died between 12 and 18 days of treatment. Oxidative damage of protein by HQO was demonstrated by measuring protein carbonyl in L. polyedrumin vivo as well as in light-exposed bovine serum albumin in vitro. In an Ames test of mutagenicity, HQO proved to be genotoxic in both light- and dark-exposed bacteria. HQO appears as a source of secondary quinalphos toxicity, which deserves further attention.     

Effect of Bauhinia racemosa stem bark on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats

The aim of this study is to investigate the antioxidant defense system induced by the methanol extract of Bauhinia racemosa L.(MEBR) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in Wister albino rats. The effects of MEBR on surface visible macroscopic (Morphometry) liver lesions (neoplastic nodules) and the levels of serum enzymes, lipid peroxidation and antioxidants were evaluated in NDEA-induced hepatocarcinogenesis in rats. In rats treated, with NDEA, significantly elevated levels of serum enzymes (SGOT, SGPT and ALP), bilirubin and decreased levels of protein and uric acid were observed. Significantly elevated amount of malondialdehyde (MDA), the end product of lipidperoxidation, indicated higher levels of lipid peroxidation, which was accompanied by significantly decreased levels of antioxidants like vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Administration of MEBR was able to suppress nodule development/hepatocellular lesion formation in rats. The extract treatment increases in antioxidant levels and dramatic decreases in lipid peroxidation levels. MEBR also produced a protective effect by decreasing the level of serum enzymes, bilirubin and increased the protein and uric acid levels. The results suggest that MEBR exert chemopreventive effects by suppressing nodule development and decreasing lipid peroxidation and enhancing the levels of antioxidants in NDEA carcinogenesis by reducing the formation of free radicals.