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Biomedical subjects

D Parmar

Publications and source records attributed to D Parmar.

32 records · Page 2Linked to original sources
PubMed1990

Cytochrome P-450 dependent monooxygenases in neuronal and glial cells: inducibility and specificity.

Distribution of the mixed function oxidases (MFO's) catalyzed by presence of multiple forms of cytochrome P-450 (P-450) was investigated in the neuronal and glial cells of the brain. The neuronal cells exhibited 2-3 fold higher activity of P-450 dependent arylhydrocarbon hydroxylase (AHH), 7-ethoxycoumarin-o-deethylase (ECOD) and 7-ethoxy-resorufn-o-deethylase (EROD) than the glial cells. Pretreatment with phenobarbital (PB) significantly increased (60-85%) the activity of ECOD in neuronal and glial cells, while a 140% increase was observed in neuronal AHH activity. Exposure to 3-methylcholanthrene (MC) resulted in a significant induction of the activity of AHH (102-345%), ECOD (115-150%) and EROD (75-120%) in the neuronal and glial cell preparations. The neurons, in general, exhibited greater sensitivity towards PB and MC induction. The present data indicate the differential sensitivity of these enzymes in neuronal and glial cells which could be used as a model to understand the selective action of certain neurotoxic agents.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1990

Search for chromosomal variations among gas-exposed persons in Bhopal.

A chromosomal survey using standard lymphocyte cultures employing different media and G-banding techniques was initiated in 1984. This study became particularly important following the tragic gaseous exposure of the population in Bhopal at midnight on 2 December 1984. We have been able to formulate a chromosomal profile for each person whom we have studied; during 1986-1988, 154 persons were examined twice. Among seemingly normal individuals, as many as 20% might possess some chromosomal abnormality; of these, 50% may develop, at a later date, some kind of pathological complication (such as tumours, recurrent abortion or transmission of defects to their offspring). The people exposed to methyl isocyanate have repeatedly shown Robertsonian translocations, mostly in acrocentric chromosomes 13 and 21. Other types of translocations have been studied among all exposed (53) and normal (101) persons; the involvement of chromosomes 5, 9, 11, 14 and 16 is statistically significant (P = less than 0.001). One of the major clinical symptoms is dyspnoea; we have estimated that almost all seriously dyspnoeic patients have developed at least two categories of chromosomal aberrations, one of which is Robertsonian translocation, in at least 10% metaphases. Our chromosomal survey will be of significance because we are able to identify people with chromosomal aberrations that might be correlated with future pathological consequences of the accident. The "chromosomal load" that can be sustained with an apparently normal phenotype can also be measured.

Accidents, Occupational↗
PubMed1989

Characterization of cerebral 7-ethoxycoumarin-O-deethylase: evidence for multiplicity of cytochrome P450 in brain.

Characterization of 7-ECOD regulated by a number of cytochrome P450 species in liver has been undertaken in brain to understand whether it can metabolize a wide variety of substrates. Maximum activity of the enzyme was recorded when 0.8 to 2.0 mg of brain microsomal protein was added to the assay mixture at pH 7.4 and incubated for 30 min. The enzyme activity was found to be localized in the microsomal fraction with the maximum activity being in the olfactory lobes and the minimum in the pons medulla region. Kinetic studies revealed that rat brain microsomes exhibited a monophasic pattern of enzyme activity with a Km value of 2 mM. Rats pretreated with phenobarbital exhibited no change in enzyme activity whereas 3-methylcholanthrene preferentially stimulated enzyme activity (two- to threefold). The differential induction of enzyme activity after MC pretreatment and the differential response of alpha-naphthoflavone and metyrapone in vitro on 7-ECOD activity in control and MC-induced microsomes of rats, mice, guinea pigs, and rabbits do suggest the possibility of the presence of multiple forms of cytochrome P450 in the brain. Significant age, sex, and species-related differences observed in the activity of ECOD have also indicated that different forms of cytochrome P450 may be regulating the enzyme activity in the brain.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

Effect of di(2-ethylhexyl)phthalate (DEHP) on hepatic mixed function oxidases in different animal species.

Administration of 2000 mg/kg of di(2-ethylhexyl)phthalate (DEHP) for a period of 7 or 15 days in rats, mice, guinea pigs and rabbits produced a differential effect as judged by alterations in body weight gain, liver weight and activities of mixed function oxidases. DEHP exposure for 7 days caused an increase in the activity of aniline hydroxylase, arylhydrocarbon hydroxylase and ethylmorphine N-demethylase in rats, mice and guinea pigs, but a decrease in that of rabbits. However, exposure for 15 days produced a smaller degree of increase in the activity of these enzymes in rats and mice and even produced a decrease in the activity of these enzymes in guinea pigs. This differential response of DEHP in various animal species suggests a species difference in the toxicity of the plasticizer.

Animals↗
PubMed1987

Studies on gamma-glutamyl transpeptidase (GGT) after di(2-ethylhexyl) phthalate (DEHP) exposure.

Administration of Di(2-ethylhexyl)phthalate (DEHP) at doses of 250, 500, 1000 and 2000 mg/kg to adult rats was found to significantly increase the activity of gamma-glutamyl transpeptidase (GGT) in liver and serum in a dose-dependent manner. The data indicate that DEHP can be hepatotoxic since an increase in serum GGT levels are indicative of hepatobiliary dysfunction and liver malignancy. An assay of GGT in serum of the individuals exposed to DEHP could be helpful in early detection of liver disorders due to this widely used plasticizer.

Animals↗
PubMed1987

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↗
PubMed1986

Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats.

Oral administration of di(2-ethylhexyl)phthalate (DEHP) in doses of 250, 500, 1000 and 2000 mg/kg to adult rats for 15 days caused a significant dose dependent decrease in the sperm count of the epididymal spermatozoa. The activity of gamma-glutamyl transpeptidase (gamma GT) and lactate dehydrogenase (LDH) was significantly increased in the animals of the treated groups. An increase in the activity of beta-glucuronidase and decrease in the activity of acid phosphatase was also observed at the highest dose of DEHP. The activity of sorbitol dehydrogenase (SDH) was found to be decreased in the animals exposed to 1000 and 2000 mg/kg of DEHP. These results suggest that DEHP can affect spermatogenesis by altering the activities of the enzymes responsible for the maturation of sperms. The reduced number of sperms may be responsible for the antifertilic effects of DEHP.

Acid Phosphatase↗
PubMed1978

Inhibition of growth of mouse ehrlich ascites by normal tissue extracts.

A dialyzable component from the aqueous extracts of mouse skeletal muscle and liver inhibited in vitro growth of a mouse Ehrlich ascites. A similar component was not detected in extracts of spleen, kidney, lung, skin, serum or small intestine. The muscle component appeared to be different from that of the liver in its resistance to heat and its stability in the culture medium. Both components however were stable on storage at 4, 23 and 37 degrees C for 72 h. Intraperitoneal injection of the muscle and liver component into mice previously innoculated with Ehrlich ascites significantly decreased tumor incidence in these animals as compared with the control.

Animals↗
PubMedDate not supplied

Aflatoxin induces depletion of activities of phase I biotransformation enzymes in growing rats.

Aflatoxins are suspected human carcinogens and are also known to possess diverse toxicological activities. In the present communication an attempt has been made to evaluate the effects of aflatoxin B1 (AFB1) on hepatic microsomal drug metabolizing enzymes in growing rats. The weanling rats were exposed to 60, 300 or 600 micrograms AFB1/kg body weight, per os, on alternate days for 4 weeks, in 0.2 ml corn oil. A significant depression in the activities of aryl hydrocarbon hydroxylase (AHH), aniline hydroxylase (AH) and aminopyrene-N-demethylase (AND) was observed at 300 micrograms and 600 micrograms doses of AFB1. However, no significant change was recorded in glutathione-S-transferase (GST) activity and total sulphydryl (SH) content upon AFB1 exposure in weanling rats. Thus, AFB1 appears to have more pronounced effect on the phase I, rather than phase II, biotransformation enzyme system in weanling rats. The depression of drug metabolizing enzymes together with suppression of immunity by AFB1, as reported earlier by us, may increase the susceptibility of the host to toxic chemicals, drugs and infectious agents, particularly during the post-natal period.

Aflatoxin B1↗
PubMedDate not supplied

Age related effects of di(2-ethylhexyl)phthalate on hepatic cytochrome P450 monooxygenases in Wistar rats.

Age related response of di(2-ethylhexyl)phthalate (DEHP) was studied by administering the plasticizer (2000 mg/kg, orally) to 3, 6 and 10 week old wistar rats for 1, 7 or 15 days and determining the activity of hepatic P450 monooxygenases. Single administration of DEHP decreased the cytochrome P450 contents and activity of arylhydrocarbon hydroxylase, aniline hydroxylase and ethylmorphine N-demethylase at all the age groups while repeated exposure induced them with maximum alterations occurring in 3 week old rats. Repeated administration for 15 days, on the other hand, caused a decrease in the cytochrome P450 content and the activity of arylhydrocarbon hydroxylase, aniline hydroxylase and ethylmorphine N-demethylase only in the 3 week old rats. The 6 and 10 week old rats exposed to the same schedule of DEHP showed an inhibition in the activity of arylhydrocarbon hydroxylase and an increase in the activity of aniline hydroxylase and ethylmorphine N-demethylase, which was however lower than that seen after 7 days of exposure to DEHP in the respective age group of animals. Our data have indicated the differences in the sensitivity of the P450 monooxygenases towards DEHP and its metabolites amongst 3, 6 and 10 week old animals.

Administration, Oral↗
PubMedDate not supplied

Technique to improve lateral cervico-thoracic radiographs.

Lateral radiographs taken during radiotherapy simulation of the upper thoracic and lower cervical region are often of poor quality because of the difference in separation seen by the incident beam. A simple method of compensating for this is the application of a thin foil of lead on the simulator that obscures the light field in the superior portion of the field. This technique has the advantage of being simple, fast and easily reproducible.

Humans↗
PubMedDate not supplied

Metabolism and disposition of cyclohexanone oxime in male F-344 rats.

Cyclohexanone oxime (CHOX), an intermediate used in the synthesis of Polycaprolactam/Nylon, was found to be rapidly absorbed and cleared from the body within 24 hours after a single oral administration of 1, 10 and 30 mg/kg of [14C]-CHOX to the adult male Fischer rats. The majority of the CHOX derived radioactivity (65-90% of the dose) was excreted in the urine. Elimination in the feces accounted for 5-10% of the dose and very low levels of radioactivity (2-3%) were retained in the tissues 24 hours after exposure. After iv administration of 1 mg/kg of [14C]-CHOX, the oxime was rapidly cleared from plasma with half-lives of 1.6 (alpha phase) and 18.2 min (beta phase). However, when CHOX was applied dermally (30 mg/kg), only about 4-5% of the dose was recovered in urine, feces and the tissues. The majority of the dose volatilized from the skin surface. However, the absorbed oxime was readily distributed and excreted, and its metabolic fate was no different than observed after oral administrations. HPLC analysis of urine showed that the majority of the radioactivity excreted was in the form of three metabolites, cyclohexylglucuronide and the monoglucuronides of cis- and trans-cyclohexane-1,2-diol. In vitro studies showed that these metabolites arise primarily by hydrolysis of the oxime to cyclohexanone which is then reduced to cyclohexanol and eliminated as the glucuronide conjugate. The cyclohexanol, in turn could be metabolized to cis- and trans-cyclohexane-1,2-diols, which excreted as their monoglucuronides.

Administration, Oral↗
PubMedDate not supplied

Hepatic mixed function oxidases and cytochrome P-450 contents in rat pups exposed to di-(2-ethylhexyl)phthalate through mother's milk.

Effects of di-(2-ethylhexyl)phthalate (DEHP) on the detoxification mechanisms of xenobiotics were investigated in neonatal rat pups of mothers receiving 2000 mg phthalate/kg daily from day 1 of birth. The nursing rat pups of mothers exposed to DEHP showed decreases in body weight gain and activities of aniline hydroxylase, ethylmorphine N-demethylase, and arylhydrocarbon hydroxylase and decreased levels of cytochrome P-450 at 21 days of age. Significant quantities of DEHP were also detected in the liver of pups in this interval. These results suggest that the livers of developing animals could be affected by the lactational transfer of DEHP, a commonly used plasticizer.

Animals↗