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Biomedical subjects

K Jeevaratnam

Publications and source records attributed to K Jeevaratnam.

At least 19 recordsLinked to original sources
PubMed2005

Adaptations of the antioxidant system in erythrocytes of trained adult rats: impact of intermittent hypobaric-hypoxia at two altitudes.

We have investigated the effects of daily exposure to intermittent hypobaric-hypoxia to two simulated altitudes (5700 m and 6300 m) in adult male rats that had been regularly swim trained in normoxia at sea level prior to exposures. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) along with the oxidative stress (OS) indices, malondialdehyde (MDA) and protein carbonyl content were measured in erythrocytes and their membranes. Hemoglobin increased in the trained animals exposed to 5700 m and in untrained rats exposed to 6300 m. Osmotic fragility in terms of hemolysis increased in altitude exposed animals. SOD increased in those exposed to 6300 m, while CAT increased in trained rats exposed to 5700 m and to 6300 m unlike in untrained rats where CAT increased only at 6300 m. GSH-Px showed varying degrees of elevation in all animals exposed to both altitudes. Erythrocyte membranes showed significant elevations in malondialdehyde (MDA) at 6300 m, while elevated protein carbonyls were noticeable at both altitudes in whole cells and membranes. These results suggest a positively associated elevation in protein oxidation with altitude in trained rats. At 5700 m, animals were less stressed, unlike at 6300 m, as seen from the magnitude of elevations in the OS indices and from the responses of the antioxidant enzymes.

Adaptation, Physiological↗
PubMed2004

Isolation and partial characterization of bacteriocins from Pediococcus species.

Lactic acid bacteria have received increased attention as a potential food preservative due to their strong antagonistic activity against many food-spoilage and pathogenic organisms. Three Pediococcus species, P. acidilactici NCIM 2292 , P. pentosaceous. NCIM 2296 and P. cervisiae NCIM 2171, were evaluated for bacteriocin production. Inhibitory substance were produced during the late growth phase and maximum production occurred at 37 degrees after 36-48 h of incubation. Bacteriocins partially purified from these species by cold-acetone precipitation at 0 degrees C and cell adsorption desorption techniques have a broad inhibitory spectrum against microorganisms, including gram-negative bacteria such as Escherichia coli and Pseudomonas. Proteolytic enzymes inactivated these peptides, but amylase and lipase did not show any effect. The bacteriocins were stable over a wide pH range (3-8) and apparently most active at pH 4.0-5.0. They were heat-stable (1 h at approximately 80 degrees C and autoclaving) at pH 5.0. No loss in activity was observed when stored under refrigeration (4-8 degrees C). Tris-Tricine SDS-PAGE revealed the molecular masses of these peptides to be between 3.5 and 5.0 kDa.

Amylases↗
PubMed2004

Molluscicidal effect of nicotinanilide and its intermediate compounds against a freshwater snail Lymnaea luteola, the vector of animal schistosomiasis.

The molluscicidal effect of nicotinanilide was evaluated and compared with niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature, young mature, and adults. Calculated values of lethal concentrations (LC50 and LC90) showed that both nicotinanilide and niclosamide as toxic against eggs, immature, and adults. The young mature stage of the snails was comparatively more tolerant to both molluscicides than the other stages. The toxicity of the intermediate compounds of nicotinanilide against the young mature stage of the snails showed them as ineffective. The mortality pattern of the snails exposed to LC90 concentration of these molluscicides showed niclosamide to kill faster (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies it may be concluded that both molluscicides are toxic against all the stages of the L. luteola snails.

Animals↗
PubMed2004

Response of antioxidant system in rats to dietary fat and physical activity.

The influence of feeding hydrogenated fat (HF) or refined peanut oil (PO) diet and regular swimming exercise on hepatic and skeletal muscle antioxidant enzymes i.e., catalase ,and glutathione peroxidase (GPX) as well as tissue lipid peroxidation was investigated in male Wistar rats. Two groups of rats were fed diet with HF or PO as the only fat source. Both the groups were further divided into 4 subgroups each according to physical activity: Two each for sedentary (HFS3, POS3) and two for swimming, HFE3 and POE3 [30 minutes a day, 6 days a week, for 3 months or HFS6, POS6, HFE6 and POE6 for 6 months. A mild increase in lipid peroxidation was observed in both liver and muscle tissues of PO-diet fed rats of E1. Swimming augmented further the lipid peroxidation in liver. GSH level was decreased in the liver of exercising rats, in contrast, it was increased in skeletal muscle by 70% in POE6 and 26% in HFE6. Compared to POS3 swimming elevated GPX activity of about 70% in liver from POE3 as well as about 60% in skeletal muscle from POE3 and POE6. The catalase activity was enhanced in muscle of HFE3 and POE3 by 250% while it remained unaltered in rats of 6 months. These data indicate an adaptive-response of antioxidant enzymes in liver and skeletal muscle to reduce oxidative stress induced by unsaturated fat (PO) and exercise.

Animals↗
PubMed1998

Physiological, biochemical and histological changes due to physostigmine in monkeys.

Physostigmine (Phy), a short-acting reversible anticholinesterase agent is considered to be a potent prophylactic antidote for the highly toxic organophosphorous (OP) compounds. The toxic effects, if any, of the probable prophylactic doses of Phy have been evaluated by studying its physiological, biochemical and histological effects in monkeys. Phy only at 100 micrograms/kg resulted in certain cholinergic signs such as salivation, lacrymation and muscular faciculations; physiological changes such as mild tachycardia, tachypnea, higher amplitude in electrical activity of the brain, clinico-chemical effects like fall in PO2, PCO2 and alkalosis and histologically an inflammatory reaction in the lungs. On the other hand, the lower dose, i.e. 50 micrograms/kg appeared to be devoid of cholinergic signs and symptoms. However, we observed a significant inhibition of both plasma and erythrocyte ChE and increase in the rectal temperature in both the Phy treated groups. From this study, Phy at a dose of 50 micrograms/kg could be inferred as a safe, sign free intramuscular dose and may probably be used in pretreatment regimen against nerve agents.

Animals↗
PubMed1995

Effect of methyl isocyanate on rabbit cardiac Na+, K(+)-ATPase.

The present study describes the effect of methyl isocyanate (MIC) on rabbit cardiac microsomal Na+, K(+)-ATPase. Addition of MIC in vitro resulted in dose-dependent inhibition of Na+, K(+)-ATPase, Mg(2+)-ATPase and K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase). Activation of Na+, K(+)-ATPase by ATP in the presence of MIC showed a decrease in Vmax with no change in Km. Similarly, activation of K+ PNPPase by PNPP in the presence of MIC showed a decrease in Vmax with no change in Km. The circular dichroism spectral studies revealed that MIC interaction with Na+, K(+)-ATPase led to a conformation of the protein wherein the substrates Na+ and K+ were no longer able to bind at the Na(+)- and K(+)-activation sites. The data suggest that the inhibition of Na+, K(+)-ATPase was non-competitive and occurred by interference with the dephosphorylation of the enzyme-phosphoryl complex.

4-Nitrophenylphosphatase↗
PubMed1994

Solid-phase extraction and reversed-phase high-performance liquid chromatographic determination of sulphur mustard in blood.

A reversed-phase high-performance liquid chromatographic method is reported for the analysis of sulphur mustard in blood with the aid of solid-phase extraction sample preparation. Sulphur mustard is extracted from blood samples (both in vitro and in vivo) of rats with a solution of 0.05 M sodium dodecyl sulphate and pre-concentrated over Sep-Pak C18 cartridges pre-coated with Tween-20. A Polygosil C18 column is used with acetonitrile-water (52:48, v/v) as mobile phase for separation and sulphur mustard was detected at 200 nm.

Animals↗
PubMed1994

In vitro and in vivo effects of methyl isocyanate on rat brain mitochondrial respiration.

The present study deals with the in vitro and in vivo effects of methyl isocyanate (MIC) on rat brain mitochondrial function. Addition of MIC to tightly coupled brain mitochondria in vitro resulted in a mild stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (fourfold) to the inhibitory action of MIC than succinate while cytochrome oxidase was unaffected. Administration of MIC subcutaneously at a lethal dose affected respiration only with glutamate+malate as the substrate (site I) and caused a 20% decrease in state 3 oxidation leading to a significant decrease in respiratory control index while state 4 respiration and ADP/O ratio remained unaffected. As both the malondialdehyde and iron contents of brain mitochondria were not altered, it may be inferred that the observed in vivo inhibition of state 3 oxidation is induced by MIC through systemic stagnant hypoxia leading to ischemia of brain, which further contributes to the cerebral hypoxia.

Animals↗
PubMed1994

Comparative toxicity of methyl isocyanate and its hydrolytic derivatives in rats. I. Pulmonary histopathology in the acute phase.

The present study describes the acute histopathological changes induced by methyl isocyanate (MIC) in the lungs of rats at 24 h after a single exposure to varied concentrations/doses of MIC by inhalation and subcutaneous (s.c.) routes and also delineates the effects due to the hydrolytic derivatives of MIC, viz., methylamine (MA) and N,N'-dimethyl urea (DMU). MIC, either inhaled or administered s.c., resulted in a wide range and extent of histopathological changes in the lungs, proportional to the exposure concentration/dose. The salient, effects of inhaled MIC are acute necrotizing bronchitis of the entire respiratory tract accompanied by varying degrees of confluent congestion, hyperemia and interstitial and intra-alveolar edema, while MIC administered s.c. led to prominent vascular endothelial damage, congestion and severe interstitial pneumonitis with apparently normal bronchial epithelium; and intra-alveolar edema only with the high dose. The only noteworthy lesion produced by MA and DMU (to some extent) was interstitial pneumonitis, suggesting their possible involvement in the subsequent inflammatory response of MIC. Except, for the endothelial changes, the overall spectrum of the histopathological lesions is quite comparable to those observed in the lungs of Bhopal victims during the acute phase.

Administration, Inhalation↗
PubMed1994

Comparative toxicity of methyl isocyanate and its hydrolytic derivatives in rats. II. Pulmonary histopathology in the subacute and chronic phases.

This paper describes the long-term (subacute and chronic) histopathological effects in the lungs of rats subjected to a single exposure to methyl isocyanate (MIC) by both the inhalation and subcutaneous (s.c.) routes as well as the role of methylamine (MA) and N,N'-dimethyl-urea (DMU), the hydrolytic derivatives of MIC in eliciting the observed changes. At the subacute phase, the intraalveolar and interstitial edema were prominent only in the inhalation group as against the more pronounced inflammatory response in the s.c. route. With the progress of time the evolution of lesions appeared to be similar, culminating in the development of significant interstitial pneumonitis and fibrosis. MA, one of the hydrolytic derivatives of MIC, also caused interstitial pneumonitis progressing to fibrosis, albeit to a lesser extent than MIC, indicating its contribution to the long-term pulmonary damage. The diffuse interstitial pulmonary fibrosis observed at 10 weeks after a single exposure to MIC by either route is of greater significance in the context of the occurrence of pulmonary fibrosis in the late autopsies of Bhopal gas victims and also clinical sequelae in some of the survivors.

Administration, Inhalation↗
PubMed1994

Acute histopathological changes induced by methyl isocyanate in lungs, liver, kidneys & spleen of rats.

Methyl isocyanate (MIC), inhaled or administered subcutaneously (sc) at lethal concentration/dose caused essentially similar histopathological changes in all the viscera except for the lungs. The observed congestion of the viscera, foci of hepatocellular necrosis with widening of Disse's spaces in the liver and tubulo-rhexis with degeneration in the kidneys are attributable mostly to the initial shock. In addition, the lungs revealed more distinct route specific patterns of histopathological lesions. Inhaled MIC caused acute eosinophilic necrosis of the bronchial epithelium and frank alveolar edema, while MIC administered sc led to prominent vascular endothelial damage and severe interstitial pneumonitis with normal bronchial epithelium. The differential loci of damage in the lungs may be attributed to the immediate contact surface available for interaction with MIC.

Animals↗
PubMed1993

Preventive effects of sodium molybdate in lead intoxication in rats.

The role of sodium molybdate (1 mg/kg, intraperitoneally, once daily) supplementation during the course of lead exposure (0.1% lead acetate in drinking water for 4 weeks) in preventing the accumulation of lead in blood and soft tissues and in restoring altered lead-sensitive biochemical variables and the levels of hepatic glutathione, lipid peroxidation, blood Na, blood K, and serum ceruloplasmin was investigated in rats. The data indicate that sodium molybdate significantly protected the uptake of lead in blood, liver, and kidneys and restored the lead-induced inhibited activity of blood delta-aminolevulinic acid dehydratase, elevation of blood zinc protoporphyrin, hepatic lipid peroxidation, and serum ceruloplasmin. The results suggest a significant role of sodium molybdate in preventing plumbism.

Animals↗
PubMed1993

Protection against cyanide poisoning by the co-administration of sodium nitrite and hydroxylamine in rats.

1. The protectiveness of combined treatment with sodium nitrite (SN) and hydroxylamine (HA) in cyanide intoxication was investigated in male rats. 2. Pretreatment with equimolar dose of SN or HA produced a significant protection against cyanide poisoning as shown by the protection index (LD50 of cyanide in protected rats/LD50 of cyanide in saline-treated rats). 3. The co-administration of SN and HA as a split dose produced an optimal and sustained methaemoglobinaemia. 4. Pretreatment with combined SN and HA administration at different time intervals offered sustained protection against cyanide and resultant cytochrome oxidase inhibition. 5. Adjunction of sodium thiosulphate (STS) in the SN+HA regimen further augmented the protection against cyanide poisoning. 6. The results suggest that pretreatment with SN+HA co-administration could significantly reduce the toxic manifestation of cyanide.

Animals↗
PubMed1993

Do the hydrolysis products, methylamine and N,N'-dimethylurea, play any role in the methyl isocyanate-induced haematological and biochemical changes in rabbits?

The subcutaneous administration of methyl isocyanate (MIC) to female rabbits, resulted in significant increases in haemoglobin concentration, erythrocyte volume fraction and leucocyte number in blood, as well as plasma total proteins, and urea. The present study was designed to investigate whether the hydrolytic products of MIC, methylamine (MA) and N,N'-dimethylurea (DMU) play any role in eliciting these changes. Both MA and DMU administered subcutaneously in an equimolar dose to that of 1.0 LD50 MIC, 2.2 mmol kg-1, had no influence on these parameters, although there was a marginal increase in the plasma urea level shortly after the administration of DMU. This study establishes that the observed haematological and biochemical changes induced by MIC intoxication in rabbits are mostly due to MIC.

Animals↗
PubMed1993

Role of lipid peroxidation in impairment of mitochondrial function at complex I by methyl isocyanate treatment of rats in vivo.

The subcutaneous administration of methyl isocyanate (MIC) in 1.0 LD50 dose in rats caused a significant effect on hepatic mitochondrial function only at complex I region of the respiratory chain. MIC administration at 1.0 LD50 dose also resulted in significant increases in malondialdehyde and ferrous ion concentration in liver mitochondria. It is suggested that the augmented lipid peroxidation in hepatic mitochondria, catalyzed by iron, possibly mobilized from intracellular stores leads to the inhibition of enzymes of mitochondrial respiration at complex I region, in vivo, in rats receiving a lethal dose of MIC subcutaneously.

Animals↗
PubMed1992

Acute toxicity of methyl isocyanate in rabbit: in vitro and in vivo effects on rabbit erythrocyte membrane.

Methyl isocyanate (MIC) interaction with the rabbit erythrocyte membrane increased the fluidity of the membrane and decreased the osmotic fragility of erythrocytes both in vitro and in vivo in rabbits intoxicated with MIC subcutaneously. MIC inhibited both acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities of erythrocytes dose-dependently in vitro, while in vivo a decreased trend in ATPase activity with unaltered AChE activity was observed. MIC also caused significant decrease in plasma sodium level with corresponding increase in potassium level in rabbits. The observed effects are due to MIC, per se, as the hydrolysis products of MIC, methylamine and N,N'-dimethylurea did not affect the erythrocyte fluidity and enzymes activities both in vitro and in vivo while they increased the osmotic fragility of erythrocytes in vivo in rabbits administered subcutaneously in equimolar concentration to MIC dosage. Inhibition of Na(+)-K(+)-dependent ATPase with altered permeability to cations and also probably water transport of plasma membrane due to MIC interaction are envisaged.

Acetylcholinesterase↗
PubMed1992

In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration.

Previous work has shown that irrespective of the route of exposure methyl isocyanate (MIC) caused acute lactic acidosis in rats (Jeevaratnam et al., Arch. Environ. Contam. Toxicol. 19, 314-319, 1990) and the hypoxia was of stagnant type due to tissue hypoperfusion resulting from hypovolemic hypotension in rabbits administered MIC subcutaneously (Jeevarathinam et al., Toxicology 51, 223-240, 1988). The present study was designed to investigate whether MIC could induce histotoxic hyperoxia through its effects on mitochondrial respiration. Male Wistar rats were used for liver mitochondrial and submitochondrial particle (SMP) preparation. Addition of MIC to tightly coupled mitochondria in vitro resulted in stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (five- to sixfold) to the inhibitory action of MIC than succinate while cytochrome oxidase remained unaffected. MIC induced twofold delay in the onset of anerobiosis, and cytochrome b reduction in SMP with NADH in vitro confirms inhibition of electron transport at complex I region. MIC also stimulated the ATPase activity in tightly coupled mitochondria while lipid peroxidation remained unaffected. As its hydrolysis products, methylamine and N,N'-dimethylurea failed to elicit any change in vitro; these effects reveal that MIC per se acts as an inhibitor of electron transport and a weak uncoupler. Administration of MIC sc at lethal dose caused a similar change only with NAD(+)-linked substrates, reflecting impairment of mitochondrial respiration at complex I region and thereby induction of histotoxic hypoxia in vivo.

Adenosine Diphosphate↗