Showing papers by "Central Drug Research Institute published in 1995"

Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart

Abstract: Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti-thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart.

Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats.

Abstract: Hexane extract of the seeds of Nigella sativa L. prevented pregnancy in Sprague-Dawley rats treated orally at 2 g/kg daily dose on days 1-10 post-coitum. Significant antifertility activity was also observed in its column fractions and subfractions. At contraceptive dose, the active hexane extract exhibited only mild uterotrophic activity comparable almost to 0.002 mg/kg dose of 17 varies; is directly proportional to-Ethinylestradiol, but was devoid of any estrogenicity in the immature rat bioassay.

Antihepatotoxic Activity of Diterpenes of Andrographis Paniculata (Kal-Megh) Against Plasmodium Berghei-Induced Hepatic Damage in Mastomys Natalensis

Abstract: Administration of an alcohol extract of Andrographis paniculata (25 mg/kg) and two of its constituent diterpenes, andrographolide and neoandrographolide (6 mg/kg/day for two weeks) showed significant antihepatotoxic action in P. berghei K173- induced hepatic damage in M. natalensis. The increased levels of serum lipoprotein-X, alkaline phosphatase, GOT, GPT and bilirubin were markedly reduced by A. paniculata and its diterpenes. In the liver, these preparations decreased the levels of lipid peroxidation products and facilitated the recovery of superoxide dismutase and glycogen. The protective effects of andrographolide were comparable to those of neoandrographolide.

Nitric oxide modulates blood-brain barrier permeability during infections with an inactivated bacterium.

Abstract: The objective of the present investigation was to study the involvement of NO in regulating the permeability of the blood-brain barrier (BBB) during infections, since NOS is known to be induced following infections. The administration of inactivated Escherichia coli (a source of lipopolysaccharide) or poly (I:C), an interferon inducer, to rats increased the permeability of BBB significantly. This increase was found to be potentiated in the presence of L-arginine, a substrate for NOS, while D-arginine had no such effect. N-nitro L-arginine methyl ester, an inhibitor of NOS, and dexamethasone, an inhibitor of NOS induction, blocked the E. coli-induced effects. These results suggest that during infections, NOS inductions causes the release of large quantities of NO, resulting in increased BBB permeability.

Oxidation and reduction of cytochrome c by mitochondrial enzymes of Setaria cervi.

Abstract: A mitochondria-rich fraction isolated from the cuticle-hypodermis-muscle system of Setaria cervi, a bovine filarial parasite, possessed substrate-coupled cytochrome c reductases and cytochrome c oxidase in appreciable activities. All these activities were located predominantly in the membranes. NADH-coupled cytochrome c reductase was more prominent than NADPH- and succinate-coupled reductases. All the three reductases exhibited marked sensitivity to rotenone and antimycin A. Salicylhydroxamic acid strongly inhibited succinate requiring reductase and cytochrome c oxidase, but the other two reductases only mildly. Sodium azide activated the reductases but substantially inhibited the oxidase activity. Potassium cyanide activated the succinate requiring reductase but did not cause any noticeable change in the activities of pyridine nucleotide linked reductases. Anthelmintics also influenced these activities but no definite correlation could be drawn regarding their mode of action.

Genetic toxicology of vinyl chloride--a review.

Abstract: Vinyl chloride (VC) is a colorless gas with a mild, sweet odor. It is extensively used in the production of vinyl chloride polymer, copolymer resin, packaging materials, wire and cable coatings as well as in industrial and laboratory intermediates. It is toxic and also carcinogenic in experimental animals. The wide human exposure to this compound in different industries throughout the world causes great concern for human health. In the present review an attempt has been made to evaluate and update the genotoxic effects of vinyl chloride based on the available literature.

Antiallergic Activity of Arbortristosides from Nyctanthus Arbortristis

Abstract: Alcohol extracts of different parts of the traditionally used Indian medicinal plant Nyctanthus arbortristist are reported to possess antiallergic activity. Arbortristoside A and C were isolated from this plant and tested for anti-passive cutaneous anaphylaxis (PCA) and mast cell stabilizing activity. Both compounds demonstrated significant anti-PCA and mast cell stabilizing activity in rats, which is comparable with that of disodium cromoglycate.

Effectiveness of α, β-arteether in acute falciparum malaria

Abstract: With the emergence of widespread chloroquine resistance and a world-wide scarcity of quinine, a search for newer antimalarial drugs has become imperative. Different derivatives of qinghaosu have been successfully tried, α, β-Arteether, an ethyl derivative of qinghaosu, was administered to 51 patients with Plasmodium falciparum malaria, in a dose of 150 mg intramuscularly once a day on 3 consecutive days. Complete parasite clearance from the peripheral blood was observed in 80% of the patients at 48 h and in 98% at 72 h. The median parasite clearance time was 2 d (range 1–4 d). 65% of the patients became afebrile within 48 h and 81% by 72 h. The mean fever clearance time was 52·04 h (standard deviation 27·09). No side effect was seen. Patients were followed-up for 4 weeks; 7 were readmitted with P. falciparum infection but it could not be ascertained definitely whether these cases were reinfections or recrudescences, α-β Arteether was a safe, effective and convenient drug for treating P. falciparum malaria. This is the first clinical study with arteether in falciparum malaria.

Antiviral Evaluation of Some Marine Plants Against Semliki Forest Virus

Abstract: Extracts of Seaweeds, seagrasses, and mangroves were screened in vitro against Semliki forest virus (SFV) on Vero cells. Anti-SFV activity was determined on the basis of inhibition of cytopathic effect (CPE). Of the 50 extracts tested, nine were found effective by inhibiting CPE from 55 to 95%. Ceriops decandra (Griff.) W. Theobald leaf showed the higher activity in vitro. The extracts effective in the in vitro assay were tested in vivo and their activity was determined on the basis of mortality and average survival time. Two extracts, Cheilosporum spectabile and Rhizophora mucronata Lam. (Rhizophoraceae), were found to be effective in protecting mice from lethal SFV infection.

Immunomodulatory Effect of Plant Extracts and Iridoid Glucosides from Nyctanthes arbortristis Against Systemic Candidiasis in Mice

Abstract: Prophylactic treatment with the ethanol (50%) extracts of the seed and root of the Nyctanthes arbortristis L. (p.o. once daily) provided significant (p < 0.05) protection of Swiss mice against Candida albicans systemic infection. Arbortristoside A and C (iridoid glucosides isolated from seed) at 5 mg/kg (p.o. once daily) enhanced protection. Arbortristoside C was, however, more protective (77.7%) and curative than arbortristoside A based upon increased MST (17 days) and reduced (3-log) CFU of C. albicans from kidney homogenates of treated mice compared to control. The prophylactic (-7 to -1 day) and therapeutic (+1 to +7 days post-infection) regimens (5 mg/kg) of arbortristoside A enhanced protection (71.4%), whereas, arbortristoside C was detrimental to mice. The protective effect of these extracts or fractions may possibly be because of the strong stimulatory activity of arbortristoside A and C elicited by significant (p < 0.001) increase in humoral and delayed type hypersensitivity (DTH) respon...

Activities and androgenic regulation of lysosomal enzymes in the epididymis of rhesus monkey

Abstract: The activities and androgenic regulation of seven lysosomal enzymes viz. acid phosphatase, N-acetyl hexosaminidase, α-mannosidase, β-glucuronidase, DNase II, RNase II and phospholipase A was established in caput, corpus and cauda segments of monkey epididymis. Estimation of enzyme activities in the epididymis of control, castrated and castrated-androgen replaced monkeys revealed that all the enzymes except RNase II showed higher activity in caput and corpus as compared to cauda. The enzymes were reduced markedly after castration and on subsequent androgen replacement there was a significant stimulation of the repressed activities, but the control levels were not restored. RNase II showed highest activity in cauda which was further elevated after castration. The possible role of these enzymes in sperm maturation and disposal is discussed.

Status of antioxidants in brain microvessels of monkey and rat.

Abstract: Levels of certain antioxidants namely reduced glutathione (GSH), ascorbic acid (Vit C), α-tocopherol (Vit E) and antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were compared in monkey and rat brain microvessels which constitute the blood-brain barrier (BBB). The BBB of both the species contains appreciable amounts of the antioxidants to protect against oxidative damage. The level of protection in rat seems to be more efficient than monkey since rat microvessels contain higher concentrations of some of the bio-antioxidants. The comparative status of enzymatic and non-enzymatic protective system against oxidation in the brain microvessels has been discussed.

Physicochemical Significance of Topological Parameters: Molecular Connectivity Index and Information Content: Part 2. Correlation Studies With Molar Refractivity and Lipophylicity†

Abstract: The studies on physicochemical significance of molecular connectivity index (1χ, 2χv) have shown that connectivity indices correlate to a greater extent with MR than with hydrophobicity (π). In order to verify these results, a set of 183 compounds of different chemical classes viz. alcohols, amines, esters, hydrocarbons, ethers, carboxylic acids etc. was chosen. In the earlier studies on this set of compounds, molecular connectivity (1χ) had been found to correlate with Log P. The correlation of valence molecular connectivity (1χ) with MR and Log P has been studied where MR showed better correlation with 2χv than Log P. The comparative correlation studies of 1χ with Log P and MR has also been carried out where 1χ shows better correlation with MR than with Log P for the total set of 183 compounds.

Effect of picroliv on antioxidant‐system in liver of rats, after partial hepatectomy

Abstract: Levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in the serum of rats increased maximally at 12 h and bilirubin at 24 h, while total proteins decreased maximally at 48 h after partial hepatectomy. The levels of total lipids, reduced glutathione, glutathione peroxidase and glutathione reductase in liver increased maximally at 12 h and catalase at 24 h, but the activities of peroxidase, glutathione-S-transferase and superoxide dismutase decreased maximally at 12 h. After the period of maximal initial increase/decrease, the changes in these parameters in liver and serum started recovering towards their prehepatectomy levels. When a similar study was performed in rats fed 12 mg/kg body wt picroliv (an iridoid glycoside fraction of Picrorhiza kurroa) once daily for 7 days, the rate of recovery of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in serum and total lipids, reduced glutathione, peroxidase, catalase and glutathione-S-transferase in liver was faster.

In vivo study of artemisinin and its derivatives against primary amebic meningoencephalitis caused by Naegleria fowleri.

Abstract: Artemisinin and its derivatives, #-arteether and sodium artesunic acid, have been evaluated for activity against experimental primary amebic meningoencephalitis and the efficacy of these com- pounds has been compared with that of the standard drug amphotericin B. In vivo experiments in Swiss mice have shown that amphotericin B at a dose of 2.5 mg/kg for 5 days produced 100% protection in the mice infected intranasally with Naegleria fowleri. Artemisinin, f-arteether, and sodium artesunic acid, even when tested at high doses (60-180 mg/ kg x 5 days), were not curative and showed only slight protection as indicated by extension of mean survival time. Naegleria fowleri is a free-living ameba known to cause a fulminating and rapidly fatal primary amebic meningoenceph- alitis (PAME) in humans (Carter, 1972). Because of the fatal outcome of most of PAME cases, efforts are continuing to de- velop new chemotherapeutic agents effective against pathogenic strains of Naegleria. Amphotericin B when administered during early infection with Naegleria fowleri, has been found to be effective in some PAME cases (Seidal et al., 1982). Recently, a claim was made that qinghaosu (QHS, artemisinin) as well as dihydroqinghaosu possess in vitro amebicidal action against N. fowleri (Cooke et al., 1987), but there are no reports on the in vivo evaluation of these compounds against experimental PAME infection. QHS and its derivatives are also fast-acting antima- larial compounds (Anonymous, 1982; Brossi et al., 1988) and have been tested for their amebicidal activity against experi- mental PAME in Swiss mice. The results are presented in this communication.