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Biomedical subjects

B Ali

Publications and source records attributed to B Ali.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of environmental pollutants on hepatocellular function in rats: 3-methylcholanthrene and Aroclor-1254.

Environmental pollutants, Aroclor-1254 (PCB) and 3-methylcholanthrene (MC), were employed in this study to investigate some aspects of the induction of hepatic drug metabolism in rats. PCB and MC treatments increased 7-ethoxyresorufin and 7-ethoxycoumarin O-deethylase activities related to cytochrome P-448. Cytochrome P-450 reductase activity was increased by PCB while no effect was observed by MC treatment. Pretreatment with PCB resulted in approximately 50% increase in the phospholipid content of the microsomes whereas MC caused no change. Liver microsomal cholesterol content was decreased while triglycerides were increased by PCB. The ratio between saturated and unsaturated fatty acids (saturation index) decreased in the total microsomes and phospholipids with PCB treatment, whereas MC did not alter the ratio, except that the major effect of MC was observed in the acyl derivatives of microsomal phosphatidylethanolamine. It is proposed that the uniaxial rotation and mobility of hemoproteins may be restricted by an increase in the saturation index of the membrane, while a decreased index may facilitate contact with reductases for electron transfer by enhanced membrane fluidity. The decreased saturation index after treatment with MC may play a role in carcinogenicity by triggering induction of free radicals.

Animals↗
PubMed1993

Effect of mancozeb on hepatic glutathione S-transferase in rat.

Oral administration of mancozeb (100 or 200 mg/kg body weight) for 7 consecutive days caused an increase in glutathione S-transferase (GST) activity in the liver of newborn, weanling and adult rats. This observed increase in GST activity was higher in weanling than in newborn and adult rats. Evaluation of acute effects at 4 and 20 h following oral administration of 200 mg mancozeb/kg showed a marginal increase in the levels of GST in adult rat liver. However, there was competitive inhibition of GST by the fungicide in vitro.

Animals↗
PubMed1993

Psychiatric morbidity: prevalence, associated factors and significance.

A cross-sectional observational systematic study was carried out on ambulatory patients at a tertiary care hospital to determine the probable prevalence, associated factors and significance of psychiatric morbidity by using an Urdu translation of the hospital anxiety and depression (HAD) scale over a period of 6 days in a week. Results showed a prevalence of 38.4% which is slightly higher than what has been generally reported (30%). Two variables, i.e., female sex and being a housewife were significantly related with the outcome. An attempt has been made to identify the probable reasons for this and some suggestions laid down for further work.

Adult↗
PubMed1993

Age-related effects in the inhibition of oxidative metabolism of xenobiotics by mancozeb.

The effect of po administration of 100 or 200 mg mancozeb/kg body weight for 7 consecutive days on microsomal mixed-function oxidase catalyzed xenobiotic metabolism was investigated in the livers of newborn weanling and adults rats. Mancozeb caused a dose-dependent inhibition in the activities of p-nitroanisole O-dealkylase and aniline hydroxylase, while the activities of aminopyrine N-demethylase and benzo(a)pyrene hydroxylase were unaffected in all the age groups. The inhibition of p-nitroanisole O-dealkylase and aniline hydroxylase, was remarkably higher in adult than in newborn and weanling rats. There was a concentration-dependent decrease in cytochrome P-450 and microsomal protein contents. This study indicates selective age-independent inhibition of hepatic monooxygenases following repeated mancozeb dosing.

Age Factors↗
PubMed1992

Characteristics of a cytosolic arylacylamidase metabolizing thiacetazone.

The N-deacetylation of thiacetazone, an antitubercular drug possessing hepatotoxic side effects, by an exclusively cytosolic arylacylamidase has been identified in the liver and kidney of rat by monitoring the appearance of its metabolite p-aminobenzaldehydethiosemicarbazone spectrophotometrically. Studies toward its characterization in liver cytosol revealed that the hydrolase possesses a broad pH optimum ranging from 6.0 to 9.0. The Km and Vmax values for the N-deacetylation of thiacetazone are 5.7 x 10(-4) M and 0.123 nmol of p-aminobenzaldehydethiosemicarbazone formed/min/mg cytosolic protein, respectively. The ability to metabolize thiacetazone was the same in the livers of cat, mouse and human, but lagged significantly in that of rat. Among the biodegradable esters examined as potential rivals of thiacetazone, only aspirin competitively inhibited thiacetazone hydrolysis (Ki = 2.1 x 10(-4) M). Discrimination of cytosolic thiacetazone N-deacetylase from nonspecific p-nitrophenylacetate esterase on the basis of their differential reactivity toward various inhibitors and activators disclosed that low concentrations of p-chloromercuribenzoate, AgNO3 and CuSO4 selectively undermine the activity of thiacetazone N-deacetylase, whereas SKF 525-A, ZnSO4 and FeCl3 are effective inhibitors of p-nitrophenylacetate esterase. However, divalent ions (Ca++ and Mg++) and EDTA failed to alter the activity of the enzyme. Besides, thiacetazone metabolism was significantly retarded upon exposure to malathion. Notably, Nal/Kl stimulated the N-deacetylase activity as a function of iodide concentration. The hydrolysis of thiacetazone in the liver and kidney remained uninduced by phenobarbital, 3-methylcholanthrene or benzo(a)pyrene (80 mg/kg, p.o., 8 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗
PubMed1991

Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic metabolism of xenobiotics in rat.

Dietary intake of petroleum ether extract of cannabis leaves by rats in doses of 158, 250 and 500 mg/kg in the first, second and third week, respectively, caused selective induction of hepatic microsomal carboxylesterases/amidases without affecting the renal hydrolytic activity. Acetanilide N-deacetylase, p-nitrophenylacetate (NPA) esterase and acetylsalicylic acid (ASA) esterase I and II (active at pH 5.5 and 7.4) were stimulated 125, 64, 82 and 60%, respectively, whereas the activities of procaine esterase and acetylaminofluorene (AAF) N-deacetylase remained unaltered. The hydrolysis of acetylcholine was also unchanged. Upon withdrawal of treatment microsomal hydrolytic activity receded to basal levels within 7 days. Curiously though, the two-fold induction of thiacetazone N-deacetylase (118%), a cytosolic hydrolase, remained largely undiminished (62%). An appraisal of the hepatic cytochrome P450 mediated oxidative metabolism revealed approximately three-fold induction of aromatic hydrocarbon hydroxylase (AHH) metabolizing benzo(a)pyrene whereas the N-demethylation of aminopyrene was unaffected. These activities were restored to normal when resin administration was discontinued.

Amidohydrolases↗
PubMed1991

Heterogeneous effects of ethylenebisdithiocarbamate (EBDC) pesticides on oxidative metabolism of xenobiotics.

Comparative evaluation of the acute effects of ethylenebisdithiocarbamate (EBDC) fungicides, mancozeb and zineb on microsomal mixed function oxidases (MFO) revealed marked substrate-dependent inhibition of oxidative metabolism of aminopyrine, p-nitroanisole and aniline in rats sacrificed 4 hr after oral administration of 100 mg mancozeb or zineb/kg body weight. Mancozeb inhibited p-nitroanisole O-dealkylase and aniline hydroxylase to a greater degree than zineb, whereas the inhibition of aminopyrine N-demethylase by the two fungicides was quantitatively comparable. Interestingly, aryl hydrocarbon hydroxylase (AHH) which exhibited maximum inhibition with mancozeb, remained unaffected following zineb administration. The time-course and dose-dependence of MFO inhibition examined 1 and 4 hr after a single oral dose of 100 mg or 250 mg zineb/kg was expressed as a dose-dependent decline in the rate of xenobiotic biotransformation at 4 hr. In vitro interaction of zineb with MFO resulted in slightly greater inhibition of aminopyrine, p-nitroanisole and aniline while AHH exhibited more pronounced decrease with mancozeb. The magnitude of inhibition of aminopyrine N-demethylase and AHH was independent of the time of preincubation of fungicides with the enzyme. Kinetic studies indicated the non-competitive nature of AHH inhibition. Chronic oral treatment with mancozeb and zineb at a dose of 250 mg/kg for 4 weeks did not modify xenobiotic biotransformations except for a slight induction of aminopyrine N-demethylase by mancozeb.

Animals↗
PubMed1990

[Mediastinal tuberculous adenopathies in Djibouti. Report of 159 cases].

One hundred and fifty-nine cases of confirmed mediastinal tuberculous adenopathy were analysed retrospectively. This series, which is the first reported in French-speaking Africa, shows that the disease is not uncommon there, and not restricted to black Africans living in Europe. The clinical symptoms are not specific. Radiography is more interesting, and the extreme scarcity of bacillys-containing expectoration encourages endoscopy. The finding of a fistula at fibroscopy confirms the diagnosis. This easy examination is particularly useful since M. tuberculosis can be grown in cultures from ground bronchial fistula biopsies in 86% of the cases. Associated tuberculous lesions in other sites are very frequent (45%), as is extension of the disease from lymph nodes to lung tissue (79%). This clinical form of tuberculosis can be treated with modern short course chemotherapy which is remarkably effective.

Adolescent↗
PubMed1990

Effect of mancozeb on hydrolytic metabolism of xenobiotics.

The present investigation reports the effect of chronic oral administration of mancozeb, a fungicide, on hepatic microsomal carboxylesterases/amidases or B-esterases responsible for hydrolytic metabolism of aspirin (acetylsalicylic acid or ASA) at pH 5.5 and 7.4, 2-acetylaminofluorene (AAF), acetanilide and p-nitrophenylacetate (NPA) and cholinesterase in rat. Oral administration of mancozeb (250 mg/kg/day) for 30 days caused significant stimulation of ASA esterase I (pH 5.5), ASA esterase II (pH 7.4), AAF N-deacetylase and acetanilide N-deacetylase in liver. However, the activities of NPA esterase and cholinesterase remained unaffected. Evaluation of induction kinetics demonstrated that the pattern and magnitude of responses of these microsomal hydrolases to mancozeb treatment for 7 days were comparable to those obtained after treatment for 30 days. The activities of hydrolases were not altered in animals killed 4 hr after an oral dose of mancozeb. Mancozeb did not affect these hydrolases in vitro.

2-Acetylaminofluorene↗
PubMed1989

Cyclic-AMP in human lung preparations.

Cyclic-AMP levels in unaffected and affected cancerous portions of human lung preparations were determined by measuring displaced 3H-cyclic-AMP from the specific binding protein by unlabeled ligand. The levels of cyclic-AMP in unaffected portions of human lungs ranged between 52-116 pmoles/g protein. Significantly higher levels of cyclic-AMP were found in lung samples affected with squamous cell carcinoma, adenocarcinoma and malignant melanoma with the mean values being 251, 290, and 509 pmoles/g protein, respectively. On the other hand, a decrease in the level of cyclic-AMP to 39 pmoles/g protein was observed in portions of lungs affected with granuloma. These results suggest that the level of cyclic-AMP in lung tissue may reflect the malignant or benign nature of the pulmonary disease.

Adenocarcinoma↗
PubMed1985

Influence of aging and poly IC treatment on xenobiotic metabolism in mice.

Cytochrome P-450-dependent and independent metabolism of xenobiotics in the liver of C57BL/10ScSn male mice was investigated in relation to age and the age-related differences in response to treatment with polyriboinosinic-polyribocytidylic acid (poly IC), an interferon inducing agent. Young (3 months), middle-aged (15 months) and old (27 months) animals were studied. Mean survival time of males of this strain is 30-33 months. Age-related changes in the metabolism of xenobiotics included significant decreases between middle and old age in activities of the microsomal P-450-dependent mixed function oxidases (MFO), aryl hydrocarbon hydroxylase (AHH) and p-nitroanisole (p-NA) O-demethylase, but not 7-ethoxycoumarin (7-Ec) O-deethylase. Analysis of P-450-independent enzymes revealed a significant decrease in the epoxide hydrolase activity in the microsomes and cytosol from old compared to middle-aged or young mice. Glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was lower in cytosols of middle-aged and old than young mice. Carboxylesterase activity was not altered by age. Hepatic microsomal protein content was significantly higher in middle-aged and old than in young mice. Intraperitoneal treatment with a single dose of 5 mg/kg poly IC 24 hours before sacrifice resulted, for mice of all age groups, in a marked inhibition of activities of all 3 microsomal cytochrome P-450-dependent enzymes, without any changes in activities of the P-450-independent enzymes. The inhibition of AHH by poly IC was much higher in old and middle-aged than in young mice, averaging 87.1%, 74.5%, and 41.9%, respectively, in the 3 age groups. Poly IC treatment increased lipid peroxidation in liver homogenates of all groups of mice. Body and liver weights were not altered in animals of the 3 age groups by poly IC treatment, but hepatic microsomal protein contents were significantly decreased.

Aging↗
PubMed1985

Identification and characterization of hepatic carboxylesterases hydrolyzing hydrocortisone esters.

The present study has provided evidence for the existence of three distinct carboxylesterases involved in the hydrolysis of steroid esters, where two enzymes are possibly responsible for the metabolism of hydrocortisone hemisuccinate (HCHS) at pH 5.5 and 8.0, and a third enzyme for the metabolism of hydrocortisone acetate (HCAC) at pH 8.0, in isolated rat liver microsomes. The activity of all three enzymes in rat liver was induced significantly by the administration of phenobarbital while no such function in enzyme activity was observed in animals receiving 3-methylcholanthrene or benzo[a] pyrene under similar experimental conditions. The increase in the activity of HCHS esterase I (HCHS-E1) active at pH 5.5, HCHS esterase II (HCHS-E2) active at pH 8.0, and HCAC esterase (HCAC-E) was approximately 7 to 8, 3- and 3-fold respectively. On the other hand, the degree of induction of nonspecific microsomal carboxylesterase acting on p-nitrophenylacetate (PNPA) was significantly less. The Km values for the hydrolysis of HCHS at pH 5.5 and 8.0 and HCAC by rat liver microsomes obtained from control rats were 2.45, 2.02 and 1.6 mM, respectively, and these Km values were not changed significantly in preparations obtained from rats treated with phenobarbital. The distinct in vitro responses displayed by hepatic microsomal steroid esterases to various inhibitors were able to distinguish three different enzymes which also differed from nonspecific carboxylesterases. The activity of HCAC-E was inhibited by NaAsO2 and AgNO3 while that of HCHS-E1 and HCHS-E2 remained unaffected. Selective inhibition of HCHS-E1 by NaF, HgCl2 and p-chloromercuribenzoate and that of HCHS-E2 by NiSO4 indicated the possible existence of different enzymes or isozymes of a carboxylesterase catalyzing HCHS hydrolysis. The effects elicited by the inhibitors on the activity of PNPA esterase were different from those observed with steroid esterases. Furthermore, the present study has also indicated species variations in the distribution of steroid esterases in the livers of rat, mouse, dog and cat.

Animals↗