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Biomedical subjects

M Chatterjee

Publications and source records attributed to M Chatterjee.

At least 109 records · Page 6Linked to original sources

Lipid peroxidation, glutathione levels and changes in glutathione-related enzyme activities in streptozotocin-induced diabetic rats.

Levels of lipid peroxidation in liver, kidney, brain and blood, liver glutathione (GSH) and several enzymes in liver tissue associated with antioxidant defence mechanism, namely Catalase (EC: 1.11.1.6), GSH reductase (EC:1.6.4.2) and GSH-S-transferase (EC: 2.5.1.18), were investigated in streptozotocin-induced diabetic rats. The single intraperitoneal injection of streptozotocin (65 mg/kg) caused a four-, eight- and seven-fold increase in lipid peroxidation in brain, liver and kidney, respectively. A decline in GSH levels both in blood (two-fold) and liver (16%) compared with normal counterparts was also observed. A marginal increase in catalase activity, a 20% decrease in GSH reductase and an increase of GSH-S-transferase activity was also found in this experimental diabetic condition. These results suggest experimental diabetes, induced by streptozotocin, can produce biochemical changes not only in pancreas but also in liver, kidney and brain tissue.

Animals↗

Protective effects of Mikania cordata root extract against physical and chemical factors-induced gastric erosions in experimental animals.

The effect of the methanolic fraction of Mikania cordata (Burm., B. L. Robinson) root extract was investigated for its possible ulceroprotective activity in male Sprague-Dawley rats. Oral administration of this extract (50, 100, or 150 mg/kg) significantly prevented the occurrence of water immersion stress-induced gastric ulcers in a dose-responsive manner. The extract also dose-dependently inhibited gastric ulcers induced by ethanol, aspirin, and phenylbutazone. The ED50 values of the extract in the above four ulcer models were found to be 95.1, 109.7, 125.5, and 136.2 mg/kg, respectively. The volume, acidity, and peptic activity of the gastric juice in pylorous-ligated rats were not altered upon administration of the extract (100 or 150 mg/kg) but it significantly and dose-dependently promoted the gastric mucus secretion in normal as well as stress- and ethanol-induced ulcerated animals. Based on these results, we conclude that M. cordata root extract possesses antiulcer activity and that the observed activity may be due to the modulation of defensive factors through an improvement of gastric cytoprotection.

Animals↗

Inhibitory effect of beta-carotene on chronic 2-acetylaminofluorene induced hepatocarcinogenesis in rat: reflection in hepatic drug metabolism.

The dietary administration of beta-carotene (BC; 100 mg/kg food) daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetyl-aminofluorene (0.05% in food). BC treatment either before initiation, during initiation and selection/promotion phases of hepatocarcinogenesis have been found to be effective in elevating hepatic microsomal cytochrome b5 (24-50%), P-450 (18-38.5%), NADPH cytochrome c reductase (17.5-43.25%) and cytosolic aryl hydrocarbon hydroxylase (60.5-63.5%) activity to a statistically significant level measured either in the hyperplastic nodule (HN) or in the non nodular surrounding liver parenchyma (NNSP) compared to carcinogen control. Moreover, BC treatment throughout the study decrease the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione S-transferase (38.9-51.22%) and microsomal UDP-glucuronyl transferase (37.3-59.1%) activities to a significant level when compared to carcinogen control rats. A decrease in the number of hyperplastic nodules and their total liver parenchyma occupied were also observed in BC treated groups. Furthermore, a direct correlation between HNs and NNSP liver areas were observed with the hepatic BC and vitamin A contents and also with the rates and patterns of hepatic drug metabolism. Our results confirm the fact that BC is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.

2-Acetylaminofluorene↗

Comparison of acetylcholine-dependent relaxation in large and small arteries of rat mesenteric vascular bed.

The relative contributions of nitric oxide (NO) to in vitro relaxation responses elicited by acetylcholine (ACh) were compared in vessels of different sizes from the rat mesenteric vascular bed. ACh elicited an endothelium-dependent relaxation in phenylephrine-contracted superior mesenteric arteries (SMA, unstretched luminal diam 650 microns), which was blocked by compounds that inhibited NO, such as hemoglobin (10 microM), methylene blue (10 microM), and NG-monomethyl-L-arginine (1 mM). In contrast, the endothelium-dependent relaxation induced by ACh in phenylephrine-contracted mesenteric resistance arteries (MRA, unstretched luminal diam 200 microns) was not blocked by hemoglobin, methylene blue, or NG-monomethyl-L-arginine. KCl (25 mM) partially inhibited the ACh-dependent relaxation in MRA. Furthermore, the ACh-dependent relaxation in MRA was selectively inhibited by the Ca(2+)-activated K+ channel blocker charybdotoxin (0.1 microM). In contrast, the ATP-sensitive K+ channel blocker glibenclamide (50 microM) did not block the ACh-dependent relaxation in MRA. We conclude that 1) NO is a major component of the ACh-dependent relaxation in SMA and 2) the ACh-dependent relaxation of MRA is resistant to NO inhibitors but sensitive to a Ca(2+)-activated K+ channel blocker. This suggests that an endothelium-derived hyperpolarization factor may be involved in the relaxation of MRA.

Acetylcholine↗

Comparative patterns of hepatic drug metabolizing enzymes and their possible correlation with chromosomal aberrations in transplantable murine lymphoma: a time course study.

The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT), cytosolic glutathione-S-transferase (GSHT) activities, and major chromosomal aberrations were evaluated over various periods of time, following tumor transplantation in male Swiss Albino mice. Changes in the above markers were studied (1) to monitor the entire carcinogenic process and (2) to test the suitability of chemopreventive exposures in terms of phase and duration of tumor growth. The microsomal cyt. P-450 content and the UDPGT activity were significantly elevated (p < 0.01-0.001) from the early stages of tumor growth while the cytosolic GSHT activity reached its highest level (p < 0.01-0.001) only 10 days after tumor transplantation. During the later stages of tumor growth all the biotransforming enzyme activities showed a downhill trend, which was significantly lower than that of their normal counterparts (p < 0.01-0.001). The frequency of different chromosomal aberrations, which were of major structural, numerical, and physiological types, increased steadily throughout the entire length of the carcinogenic process (30 +/- 2 days).

Animals↗

A novel effect of selenium on streptozotocin-induced diabetic mice.

The effect of oral administration of sodium selenite on glucose homoeostasis was studied in male Swiss albino mice 6 weeks after they were made diabetic with streptozotocin. Diabetes caused hyperglycaemia (2.5-fold), a marked decrease (4.5-fold) in liver glycogen, a 4-fold increase in the glucose-6-phosphatase activity and significant decrease in plasma insulin levels and protein kinase activity. Although selenium administration in control animals showed no significant effect on various parameters measured, selenite treatment of diabetic mice restored these parameters to near control values. Thus the results show insulin-like in vivo action of selenium in diabetic mice.

Animals↗

Enhanced erythropoietin and suppression of gamma-glutamyl transpeptidase (GGT) activity in murine lymphoma following administration of vanadium.

Administration of vanadium as ammonium monovanadate (0.005 microgram/0.1 ml/mouse/day) was found to reduce the tumor cell proliferation in the host mice bearing Dalton's lymphoma. The high activity of gamma-glutamyl transpeptidase (GGT), a neoplastic marker, was seen in the host cells bearing lymphoma. Vanadium effectively prevented an increase in activity of gamma-glutamyl transpeptidase and maintained a sustained low activity of this enzyme. In addition, an improvement of the hematological aspects of the mice and almost fourfold elevation of erythropoietin (Epo) was obtained following vanadium treatment. This increase in Epo activity may play a vital role in regulating the growth of cellular neoplasia. The present study further confirms the antitumorigenic potential of vanadium in the control of tumor progression in lymphoma via modulating several factors involving erythropoiesis and may emerge as a new chemopreventive agent for the future.

Animals↗

Mechanism of action of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and an eIF-2 kinase (dsI).

Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.

Aminopeptidases↗

Role of human placental extract on succinic dehydrogenase activity in carrageenin-induced edema in rats in vivo and its effect on erythrocyte lysis, platelet aggregation and trypsin activity in vitro.

Significant increase of liver succinic dehydrogenase (SDH, EC 1.3.99.1) activity was produced by carrageenin-induced edema in rats. Pretreatment with human placental extract inhibited the increased liver SDH activity in a dose-dependent manner. Placental extract was found to have little or no effect on the liver SDH activity in normal rats. Furthermore, heat-induced erythrocyte lysis was inhibited to a substantial extent by the extract and was found to be dose-responsive. However, adenosine diphosphate (ADP)-induced platelet aggregation and trypsin activity were not changed by the placental extract in vitro. The study indicates that the membrane stabilization and depletion of adenosine triphosphate (ATP) synthesis may contribute to antiinflammatory effect of the extract.

Animals↗

A fluorescence anisotropy study of stabilizing effect of tri- and tetra- nitrovasodilatory drugs on DPPC liposomal membrane.

Glyceryl trinitrate (GT) and pentaerythritol tetranitrate (PT) are two vasodilatory drugs. The physical properties of the membrane lipid matrix, which determine the structure and function of the membrane-bound proteins, generally control the perturbation mechanism of these drugs. Thus, physical interaction of these drugs with membrane lipids is very crucial for their clinical use, different cellular processes, as well as for targetted drug delivery systems. In the present paper, we have reported for the first time the interaction between these drugs and the lipid molecules in the liposomal system of dipalmitoylphosphatidyl-choline (DPPC), as measured by steady-state fluorescence anisotropy using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescent probe. Our results show that by dissolving in the lipid matrix these two drugs effectively stabilise the liposomal membrane: the effect being more in case of GT than in PT, indicating that the rigidifying effect is independent of the number of nitrate groups of the two drugs. This effect increases with the increase in drug concentration, implying solubilisation of all drug molecules. Though our in vitro study has more physical significance than a physiological one, the results obtained here may be used to interpret the effects that are observed in vivo.

1,2-Dipalmitoylphosphatidylcholine↗

Physiological overshoot and the compound action potential.

The sensitivity of the compound action potential (CAP) of the auditory nerve of the Mongolian gerbil (Meriones unguiculatus) to an added signal was studied as a function of the state of adaptation to a masker. The masker consisted of a train of tone bursts. A signal was added to one of the bursts and the threshold for detecting the signal was determined using a two-interval forced-choice technique. With a signal at the same frequency as the masker, there was little or no change in threshold with increasing adaptation to the masker, i.e., with the signal applied at masker onset or later on in the train. With a signal at a different frequency, considerably higher thresholds were obtained in the unadapted state than in the adapted state, a situation that appeared to resemble psychophysical overshoot phenomena. However, the interpretation of this result was complicated by the observation that the CAP response to a two-frequency stimulus is a sum of two slightly desynchronized waveforms arising from different cochlear regions. Synchronizing the two waveforms reduced the 'overshoot', but still resulted in higher thresholds in the unadapted state. The differences in threshold are accounted for by considering the changing signal-to-noise ratios at different states of adaptation. Possible relationships to psychophysically observed overshoot are discussed.

Acoustic Stimulation↗

Antitumor activity of Parthenium hysterophorus and its effect in the modulation of biotransforming enzymes in transplanted murine leukemia.

The methanolic flower extract of Parthenium hysterophorus has been found to have antitumor effects in host mice bearing transplantable lymphocytic leukemia. The effect was more pronounced in terms of tumor size, tumor spread, and survival of the host. The potentiating effect of the extract was supported by biochemical autopsies relating to markers like glutathione level, cytochrome P-450 content, glutathione transferase, and UDP-glucuronyl transferase in liver tissue of the host cells. These neoplastic markers showed substantial alteration leading to slow development of tumors and increased survival of the host bearing lymphocytic leukemia.

Animals↗

Elevated lipid peroxidation, decreased glutathione levels and changes in glutathione-related enzymes in rats treated with human placental extract.

The in vivo effects of human placental extract (1-4 ml/kg) on hepatic lipid peroxidation, blood and liver glutathione (GSH) levels and several enzymes associated with the antioxidant defence mechanism; i.e., catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, together with some blood biochemical responses were investigated in rats. At an optimal dose level (4 ml/kg), a single acute intraperitoneal administration of the extract caused a significant enhancement (49.9%; p < 0.001) of lipid peroxidation with a decline in GSH level both in blood (45.1%; p < 0.001) and liver (61.0%; p < 0.001) in comparison to control animals. Activities of catalase, glutathione peroxidase and glutathione reductase were inhibited in a dose-responsive way by the treatment with the extract which also increased the activity of glutathione S-transferase in a dose-dependent manner. The extract was found to be hepatotoxic in terms of elevation of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum lactate dehydrogenase and blood methemoglobin concentration. Results of this study suggest the adverse consequences of the administration of the extract due to its substantial ability to alter normal cellular processes.

Animals↗

Selective enhancement of glutathione S-transferase activity in liver and extrahepatic tissues of rat following oral administration of vanadate.

The effect of oral administration of vanadate (100, 200 and 400 nM for 30 days) on the activity of the detoxifying enzyme system glutathione S-transferase (GST) in rat liver and in several extrahepatic tissues was examined. Vanadate showed a high activity as GST inducer in liver and in small intestine mucosa followed by large intestine mucosa and kidney in a dose-dependent manner. No significant alterations in GST activity were observed in forestomach and lung tissues after vanadate. Vanadate treatment that resulted in an enhancement of GST activity impaired neither hepatic nor renal function as evidenced by serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, urea, and creatinine. Since the ability to induce an increase of detoxifying enzyme activity by anticarcinogenic agents was found to correlate with their activity in the inhibition of tumorigenesis, the trace element vanadium might be considered a potential cancer chemopreventive agent.

Administration, Oral↗

Protective role of vanadium in the survival of hosts during the growth of a transplantable murine lymphoma and its profound effects on the rates and patterns of biotransformation.

Vanadium, as ammonium mononium monovanadate, has been found to have anticarcinogenic effect in host mice bearing a transplantable ascitic lymphoma. The potentiating effect of vanadium was supported by biochemical analysis of autopsies relating to markers like microsomal cytochrome P-450, UDP glucuronyl transferase (UDPGT) and cytosolic glutathione-S-transferase (GSHT) in the hepatic tissue of the hosts, which showed substantial alterations in the extent of tumor regression as compared to their lymphoma and normal counterparts, prolonging the survival of the hosts.

Animals↗

Prenatal diagnosis of atrioventricular canal malformations with up-to-date echocardiographic technology: report of 14 cases.

Fourteen fetuses with atrioventricular canal malformations were examined by two-dimensional echocardiography, pulsed-wave Doppler echocardiography, and color Doppler flow mapping. Eleven fetuses had complete and three fetuses had partial atrioventricular canal malformations. Nonimmune hydrops fetalis was associated with six cases, and fetal arrhythmia was seen in three cases. With two-dimensional echocardiography, the atrioventricular canal malformations could be diagnosed accurately. The inclusion of color Doppler flow mapping, however, provided additional hemodynamic information that was important from the prognostic point of view. Incompetence of atrioventricular valves could be demonstrated in 10 of 14 cases by Doppler echocardiography. In nine cases, detailed Doppler echocardiographic evaluation of the regurgitation jet was possible. The proportion of systolic time during which atrioventricular valve insufficiency was demonstrated was related to the occurrence of nonimmune hydrops fetalis. When insufficiency of atrioventricular valves was associated with hydrops (four cases), a pansystolic insufficiency was always present. In cases without hydrops (five), regurgitation was confined to early systole. Thus a reliable method for semiquantitative evaluation of the degree of insufficiency seems to have been found. Moreover, an association appeared to exist between the occurrence of hydrops fetalis and the proportion of atrial area that was taken up by regurgitant jet area, as determined by planimetry in the four-chamber view. Prenatal diagnosis was confirmed by autopsy or neonatal cardiac evaluation. Only one neonate survived in our series. Two were stillborn, four died during the neonatal period, two died during infancy, and pregnancy was electively terminated prematurely in five cases. Eight fetuses were found to have a karyotypic abnormality.

Adult↗