Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Catalysis & Leishmania donovani. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

Ascorbic acid--a naturally occurring mediator of lipid peroxide formation in rat brain.

Abstract: Male albino rats (body wt. 3G50g) drawn from the CDRI Stock Colony were fasted overnight. They were decapitated and their whole brains were excised and washed with cold 150 mM-potassium chloride. Homogenates (10% w/v) were prepared in chilled 150 mwpotassium chloride and centrifuged at 80Oy for IOmin. The supernatant fluid was centrifuged at 18,000g for 15 min and the resultant supernatant fluid was centrifuged at 106,000 for 1 h to recover the organelle-free cytosol fraction. The pellet sedimenting at 18,OOOy was suspended in 150 mM-potassium chloride and washed by centrifugation and finally suspended in 150 mM-potassium chloride to a final protein concentration of 6 mg/ml. This was referred to as 'mitochondrial fraction'. Assay of lipid peroxides. Samples of 0.5 ml of the source of pro-oxidant were mixed with 0.25 ml of the mitochondrial fraction. The flasks containing the mixture were shaken in a metabolic shaker (120 strokes/min) for 3 h a t 37°C. One millilitre of 10% w/v trichloroacetic acid was added and after thorough mixing, the reaction mixture was centrifuged at 800 y for 10 min. Samples (1 ml) of the clear supernatant fluids were mixed with 1 ml 0.67% w/v 2-thiobarbituric acid and held in a boiling water bath for 10 min, cooled and diluted with 1 ml distilled water. The absorbance of the solution was read at 535nm and results expressed as malonyldialdehyde using 1.56 x lo5 as extinction coefficient (UTLEY et a/., 1967). Chemical esfimutions. Protein was estimated according to LOWRY et al. (1951), sulphydryl groups according to ELLMAN (1959), ascorbic acid according to ROE & KUENTHEK (1943) (bromine as oxidizing agent), ACh according to HESTRIN (1949) and amino acids according to MOORE & STEIN (1948). Preparation and assay of ascorbic acid oxidase (EC 1.10.3.3). The enzyme was prepared from the bottle gourd (Lagenaria siceraria) and assayed by the procedure Of LOVETT-JAMISON & NELSON (1940).

Role of ethnic variations in TNF-α and TNF-β polymorphisms and risk of breast cancer in India.

Abstract: TNF-α and -β, the multi-functional pro-inflammatory cytokines, are known to play important roles in both tumor progression and destruction based on their concentrations. Growth factors and various stimuli such as cytokines regulate proliferation of the breast epithelial cells. Therefore, the polymorphisms in the genes encoding these signaling molecules could affect the risk of breast cancer. We have investigated selected genetic polymorphisms in TNF-α promoter (rs1800629, −308 G>A and rs361525, −238 G>A) and TNF-β intron 1 (rs909253, +252 A>G) in ethnically two different case–control groups from India. The study included 200 cases and 200 controls from an Indo-European (North Indian) group, and 265 cases and 237 controls from a Dravidian (South Indian) group. Genotyping of a total of 902 individuals was done by direct DNA sequencing. None of the polymorphisms showed significant association with breast cancer in the Indo-European group; however, all the three polymorphisms showed strong association with breast cancer in the Dravidian group. Further, sub-group analysis in the Indo-European group showed no significant difference between pre-menopausal cases and controls or between post-menopausal cases and controls at any of the loci analyzed. However, all the polymorphisms in the Dravidian group were significantly associated with pre-menopausal but not with post-menopausal breast cancer. In conclusion, TNF-α and -β polymorphisms are strongly associated with breast cancer in the Dravidian but not in the Indo-European group.

Desmodium gangeticum: a potent anti-ulcer agent.

Abstract: The present study was designed to investigate anti-ulcerogenic property of ethanolic extract of Desmodium gangeticum (DG) against cold restraint (CRU, 2 hr cold restraint stress), aspirin (ASP, 150 mg/kg orally), alcohol (AL, absolute alcohol 1 ml/200gm) and pyloric ligation (PL, 4 hr pylorus ligation) induced gastric ulcer models in Sprague Dawley rats, and histamine (HST, 0.25 mg/kg) induced duodenal ulcer in guinea pigs. We found that DG at a dose of 200mg/kg, (orally), markedly decreased the incidence of ulcers in all the above models. DG showed significant protection against CRU (68.37%), AL (88.87%), ASP (38.2%), PL (40.63%) and HST (63.15%) induced ulcer models, whereas standard drug omeprazole (OMZ) showed protection index of 83.86, 56.35, 70.31 and 84.21%, respectively in CRU, ASP, PL and HST models. Sucralfate as standard drug showed 92.64% protection in AL model. DG significantly reduced acid secretion 41.61%, whereas OMZ produced 43.13% reduction. Treatment with DG showed increase in mucin secretion by 56.17%, whereas OMZ showed 12.45% increase. Anti-ulcer effect of DG may be due to its cytoprotective effect along with antisecretory activity and could act as a potent therapeutic agent against peptic ulcer disease.

Antileishmanial activity mediated by apoptosis and structure-based target study of peganine hydrochloride dihydrate: an approach for rational drug design

Abstract: Objectives: The aim of this study was to resolve the putative pathway responsible for death induced by peganine hydrochloride dihydrate isolated from Peganum harmala seeds at cellular, structural and molecular level in Leishmania donovani, a causative agent of fatal visceral leishmaniasis. Methods: The mode of action was assessed using various biochemical approaches including phosphatidylserine exposure, estimation of mitochondrial transmembrane potential and in situ dUTP nick end labelling staining of nicked DNA in the parasite. Molecular modelling and molecular dynamics studies were conducted with DNA topoisomerase I to identify the target of peganine hydrochloride dihydrate mediating apoptosis. Further, DNA topoisomerase I inhibition by peganine hydrochloride dihydrate was also assessed using an L. donovani topoisomerase I relaxation assay. Results: Peganine hydrochloride dihydrate, besides being safe, was found to induce apoptosis in both the stages of L. donovani via loss of mitochondrial transmembrane potential. Molecular docking studies suggest that a binding interaction with DNA topoisomerase I of L. donovani (binding energy of 279 kcal/mol) forms a stable complex, indicating a possible role in apoptosis. The compound also inhibits L. donovani topoisomerase I. Conclusions: The compound induces apoptosis in L. donovani and inhibits DNA topoisomerase I.