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Biomedical subjects

G B Singh

Publications and source records attributed to G B Singh.

At least 37 records · Page 2Linked to original sources

Effect of extraneous supplementation of ascorbic acid on the bio-disposition of benzanthrone in guinea pigs.

The bio-elimination and organ retention of orally administered [14C]benzanthrone, an anthraquinone dye intermediate, were determined in control and ascorbic acid-supplemented guinea pigs. Urinary excretion of benzanthrone in control and ascorbic acid-treated animals during 96 hr was 27.9 and 30.5%, respectively, with peak elimination at 48 hr. Faecal elimination in control and supplemented animals during 96 hr was 24.5 and 38.8%, respectively, with a peak at 48 hr. The organ retention of radiolabelled benzanthrone at the end of 96 hr was of the order of 39% in control animals (gastro-intestinal tract 16%; liver 22%; testis 1.2%); ascorbic acid supplementation reduced benzanthrone retention to 19.5% (gastro-intestinal tract 12.7%; liver 6.8%). Overall, pretreatment of guinea pigs with ascorbic acid caused a 32% enhancement in the clearance of radiolabelled benzanthrone through the urine and faeces, while organ retention was reduced by about 50%. A prophylactic dose of ascorbic acid may prevent benzanthrone-induced toxic symptoms in exposed workers.

Animals↗

Anti-inflammatory activity of oleanolic acid in rats and mice.

Oleanolic acid displayed anti-inflammatory activity in carrageenan and dextran-induced oedema in rats. It elicited marked anti-arthritic action in adjuvant-induced polyarthritis in rats and mice and in formaldehyde-induced arthritis in rats. Oleanolic acid checked the inflammation-induced increased serum transaminase levels. It reduced exudate volume and inhibited leucocyte infiltration in carrageenan-induced pleurisy in rats. It is devoid of any analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the parturition time in pregnant rats or castor oil-induced diarrhoea in rats. Oral LD50 was found to be greater than 2 g kg-1 in mice and rats.

Adrenalectomy↗

The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate.

Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.

Administration, Oral↗

P-aminodiphenylamine induced biochemical changes in sex organs of male albino rats.

Intraperitoneal administration of p-aminodiphenylamine (p-ADPA), an aromatic amine of wide industrial applications, / 42.5 mg/kg body weight for 180 days significantly decreased the activities of testicular lactate dehydrogenase and hyaluronidase and lactic acid content indicating arrest of spermatogenesis. Patchy necrosis of the testis was confirmed histopathologically. No change in testicular cholesterol, fructose content of coagulating glands and dorso-lateral prostate and activities of alkaline phosphatase in seminal vesicle and acid phosphatase in ventral prostate support normal androgenic status.

Animals↗

Bio-elimination and organ retention profile of benzanthrone in scorbutic and non-scorbutic guinea pigs.

The retention and bio-elimination of benzanthrone (BA) in scorbutic and non-scorbutic guinea pigs was investigated to understand the protective role of ascorbic acid. Oral intubation of 14C-BA to scorbutic and non-scorbutic guinea pigs showed a total recovery of around 91% radioactivity through urine, faeces and tissues. Recovery of radiolabelled BA through urine (28%) and faeces (22%) up to 96 hrs averaged 50%, whereas residual radioactivity in liver and testis experienced a recovery of 29% in scorbutic animals. In non-scorbutic animals there was an increased recovery of radioactivity through urine (37%) and faeces (31%) with a decrease in retention (10%) in liver and testis. These results suggest that ascorbic acid facilitates the mobilization and bio-elimination of BA and thereby can decrease the toxicity of the compound.

Animals↗

Interaction of benzanthrone with cytochrome P450: altered patterns of hepatic xenobiotic metabolism in rats.

Benzanthrone, an anthraquinone dye intermediate, is commonly used for the synthesis of a number of polycyclic vat and disperse dyes. Our prior studies have shown that benzanthrone can be metabolized by rat hepatic microsomal cytochrome P450 (P450) (Biochem. Int., 18, 1989, 1237). In this study, the interaction of benzanthrone with rat hepatic microsomal P-450 and its effect on xenobiotic metabolism have been investigated. Parenteral administration of benzanthrone (40 mg/kg body weight) for 3, 7, or 21 days caused no change in the relative body weight or organ weight of rats. The levels of P450 were found to be reduced (33%-50%) in all the benzanthrone-exposed animals at all the time periods. In vitro addition of benzanthrone caused a spectral change with oxidized P450 and concentration-dependent reduction in the carbon monoxide spectrum of dithionite-reduced P450. The addition of benzanthrone to hepatic microsomes prepared from phenobarbital-treated rats resulted in spectral changes characterized by an absorbance maximum at 397 nm indicative of type I binding. In vitro addition of benzanthrone showed a concentration-dependent inhibition of hepatic aminopyrine N-demethylase (APD) and ethoxyresorufin-O-deethylase (ERD) activities with respective I50 values of 9.5 x 10(-4) and 8.0 x 10(-5) M. However, the inhibition of aryl hydrocarbon hydroxylase (AHH) even at the highest concentration of benzanthrone (10(-2) M), was of the order of only 29%. In vivo administration of benzanthrone also led to the inhibition of APD, AHH, and ERD activities at all treatment times although the magnitude of inhibition was of a lower order.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata.

Suspensions of rat peritoneal polymorphonuclear leukocytes (PMNL) elicited with glycogen were stimulated by calcium and ionophore to produce leukotrienes and 5-HETE from endogenous arachidonic acid (AA). We investigated the effect of ethanolic extracts of the gum resin exudate of Boswellia serrata. A concentration-dependent inhibition of LTB4 and 5-HETE production by different charges of exudate extracts were found. All products of the 5-lipoxygenase (5-LOx) from endogenous arachidonic acid (AA) in PMNL were reduced to the same extent by the extracts tested. The ethanolic extract of the gum resin also decreased 5-LOx mediated metabolisation of exogenously added AA to LTB4 and 5-HETE. Since steroidal-type anti-inflammatory drugs do not exert an immediate effect in the test system used, we conclude that the activity of the 5-LOx itself represents the side of inhibition by the gum resin extract. Therefore, an inhibition of 5-LOx catalysed mediator synthesis might be involved in the previously reported anti-inflammatory activity in vivo.

Animals↗

Metabolic disposition of 14C-metanil yellow in guinea pigs.

The absorption, metabolism and excretion of 14C-metanil yellow was studied in guinea pigs. Following administration of a single po dose of 5 mg dye (7.6 mu Ci)/kg body weight, 83.4% was excreted through urine and feces within 96 h with the majority accounted for in feces. Liver, kidney and spleen did not have marked accumulation of counts, whereas testes and gastrointestinal tract retained 1.9 and 9.7% of the radioactivity, respectively. Analysis of urine and feces detected 2 azo-reduction metabolites of metanil yellow which were characterized by TLC and IR, NMR and mass spectroscopic studies as metanilic acid and p-aminodiphenylamine.

Animals↗

Hypotensive action of a Coscinium fenestratum stem extract.

A 50% ethanol extract of Coscinium fenestratum stem material (AECF) has been found to possess hypotensive action in anaesthetised dogs, rats and guinea pigs in a dose-related pattern. The fall in blood pressure was not modified by alpha and beta adrenergic blockers, cholinergic and histaminergic antagonists or by ganglion blocking agents. The effect was more pronounced in spinal-transected animals. AECF non-specifically inhibited the pressor responses to epinephrine, norepinephrine, DMPP and depressor responses to acetylcholine and histamine. AECF failed to exhibit any hypotension when administered via cannula into the lateral cerebral ventricle. Given orally to mice, AECF did not exhibit grossly observable central nervous effects up to doses of 800 mg/kg. The oral LD50 was estimated to be 1200 mg/kg in mice.

Animals↗

Testicular toxicity of di-n-butyl phthalate in adult rats: effect on marker enzymes of spermatogenesis.

Di-n-butyl phthalate (DBP) was administered to adult male rats by gavage at the doses of 250, 500 and 1000 mg/kg body weight/day for 15 days. A significant decrease in epididymal spermatozoa counts was observed at 500 and 1000 mg/kg doses of DBP. The activity of sorbitol dehydrogenase was found to be significantly decreased while that of lactate dehydrogenase, gamma-glutamyl transpeptidase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase, significantly increased in the animals exposed to 500 and 1000 mg/kg of DBP. Decrease in the activity of acid phosphatase was also observed at all dose levels. Histopathological studies revealed marked degeneration of seminiferous tubules, further confirming testicular toxicity of DBP. The results suggest that testicular atrophy caused by DBP is associated with an alteration in the activities of enzymes related with specific events of spermatogenesis.

Animals↗

Biochemical toxicology of argemone oil. IV. Short-term oral feeding response in rats.

Consumption of edible oils contaminated with Argemone mexicana seed oil is known to cause various clinical manifestations. In the present study, the effect of dietary intake of argemone oil on histopathological changes, haematological indices and selected marker parameters of toxicity was investigated to observe the exact sites and mode of action of argemone oil in rats. Histopathological changes in the liver showed increased fibrosis, hyperplasia of bile ducts and congestion in a few portal tracts. Lungs of argemone oil-fed animals indicated congestion and thickening of interalveolar septa. Alveolar spaces were disorganised and irregular. Kidneys showed vascular and glomerular congestion and patchy tubular lesions. At 30 days only mild congestion was noted in the myocardium. Cardiac muscle fibres showed degenerative changes at 60 days which were more marked in the auricular wall. Haematological examination showed appearance of anaemia in experimental animals. Hepatic alkaline phosphatase, alanine transaminase and aspartate transaminase activities were inhibited by 30, 29 and 29% after 30 days of argemone intake along with concomitant enhancement in serum by 27, 29 and 66%, respectively. Liver showed decrease in glutathione (32-63%) content along with significant stimulation of lipid peroxidation (49-105%) in argemone-intoxicated animals. These results suggest that liver, lungs, heart and kidneys are the target tissues of argemone oil toxicity and that membrane destruction may be a possible mode of action.

Animals↗

Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis.

The effect of boswellic acids on bovine serum albumin (BSA)-induced arthritis in rabbits was studied. Oral administration of boswellic acids (25, 50 and 100 mg/kg/day) significantly reduced the population of leucocytes in a BSA-injected knee and changed the electrophoretic pattern of the synovial fluid proteins. The local injection of boswellic acids (5, 10 and 20 mg) into the knee 15 min prior to BSA challenge also significantly reduced the infiltration of leucocytes into the knee joint, reduced the infiltration of leucocytes into the pleural cavity and inhibited the migration of PMN in vitro. The leucocyte-inhibitory activity of boswellic acids was not due to its cytotoxic effect. The boswellic acids did not show any detergent or surfactant properties.

Animals↗

Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol).

8,24-Euphadien-3 beta-ol (euphol) on i.v. administration was found to exhibit a hypotensive activity in normotensive anesthetised dogs and rats which varied from a slight to a marked degree depending upon the dose range. Euphol inhibited various autonomic pressor and depressor responses. The hypotensive effect was not affected in dogs pretreated with atropine, antistine, and beta-blockers and in bilaterally vagotomised and carotid sinus denervated animals. The fall in blood pressure was enhanced in spinal transected and eviscerated dogs and after ganglion blockade with hexamethonium. Localisation of euphol to central cardiovascular loci displayed no effect on blood pressure. The LD50 in mice was found to be 1500 mg/kg i.p. and greater than 2 g/kg by the oral route.

Animals↗

Benzanthrone: a new substrate for hepatic microsomal cytochrome P-450.

The metabolism of benzanthrone, a commonly used dy intermediate, by rat hepatic microsomes was investigated using thin layer chromatography (TLC) analysis. Incubation of benzanthrone with hepatic microsomes in the presence of NADPH generating system produced at least seven fluorescent metabolites on TLC plates. TLC spots numbered II, III, IV, V and VI were the major metabolites obtained from hepatic microsomes with the Rf values of 0.53, 0.45, 0.38, 0.33 and 0.26, respectively. Metabolites VII and VIII were faint bands with Rf values of 0.08 and 0.04, respectively. Preincubation of hepatic microsomes with either 1-benzyl-imidazole (10(-4)M) or SKF-525 A (10(-4)M) or metyrapone (10(-3)M) or flushing with carbon monoxide substantially inhibited the benzanthrone metabolism. alpha-Naphtho-flavone (10(-4)M) did not cause any change in hepatic microsomal metabolism of benzanthrone. Oral administration of benzanthrone to animals yielded at least six urinary metabolites. TLC spots numbered II, III, IV, V and VI in the urine were same as those of hepatic microsomal metabolites. However, one of the urinary metabolite numbered IX which stays at the origin of TLC plate with the Rf value of 0.05 may be a conjugate. Our results suggest that benzanthrone acts as a substrate for hepatic heme protein, cytochrome P-450 and that some of the metabolites are excreted in urine.

Animals↗

Effect of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leucocyte migration.

Effect of alcoholic extract of salai guggal (AESG) was studied on cellular and humoral immune responses in mice and leucocyte migration in rats. Oral administration of AESG strongly inhibited the antibody production and cellular responses to sheep red blood cells in mice. It inhibited the infiltration of polymorphonuclear leucocytes and reduced the volume of pleural exudate in carrageenan induced pleurisy in rats. It showed no cytotoxic effect.

Animals↗

Urinary excretion of connective tissue metabolites under the influence of a new non-steroidal anti-inflammatory agent in adjuvant induced arthritis.

The therapeutic effect of boswellic acids and salai guggal in adjuvant induced arthritic rats in relation to urinary excretion of connective tissue metabolites viz. hydroxyproline, hexosamine and uronic acid was thoroughly investigated. Compared to controls, the arthritic animals showed an increase in the excretion of these metabolites in urine. The elevated levels of urinary hydroxyproline (free, total, nondialysable and dialysable), hexosamine and uronic acid in the arthritic animals were found to be slightly decreased in the acute phase and significantly decreased in the chronic phase of the disease following the administration of boswellic acids or salai guggal. The results of the investigation indicated that both these anti-inflammatory drugs could offer a partial protective action against changes induced by adjuvant induced arthritis.

Animals↗

Effect of testosterone on the testicular atrophy caused by di(2-ethylhexyl)phthalate (DEHP).

The involvement of testosterone in di(2-ethylhexyl)phthalate (DEHP) induced testicular injury has been examined by coadministration of testosterone (1 mg/kg) along with DEHP (2000 mg/kg) daily for 15 days. The coadministration of testosterone and DEHP appears to have prevented the testicular injury as judged by the biochemical and histopathological changes. The sperm count and the activity of the testicular enzymes, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), beta-glucuronidase and acid phosphatase, related with the maturation of sperm, which were significantly altered by DEHP treatment were found to be within normal levels after the combination treatment of DEHP and testosterone. The histopathological studies also showed more or less normal spermatogenic events. The results of this study have suggested the involvement of testosterone in DEHP induced testicular atrophy.

Animals↗