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Biomedical subjects

Q Rahman

Publications and source records attributed to Q Rahman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Evidence that exposure of particulate air pollutants to human and rat alveolar macrophages leads to differential oxidative response.

Macrophages and inflammatory cells generate active oxygen species in the process of killing and degrading microorganisms. Air pollutant particles may be ingested by macrophages and stimulate the same mechanisms to produce a long term oxidative burden to the lung if particles are not degraded. In the present study human and rat alveolar macrophages (AM) were compared in their response to inhaled particles using luminol dependent chemiluminescence (CL) and peroxide dependent CL assays. Cytotoxicity was measured by the release of lactate dehydrogenase (LDH) activity in the supernatant. Human AM produced more oxidants than rat AM whether, unstimulated, after addition of particles or addition of particles then peroxidase. Human AM also had a different spectrum of response to the same particles. Our results suggest that human macrophages produce more reactive oxygen species in respond to particles than rat AM.

Adolescent↗
PubMed1997

Effect of kerosene and its soot on the chrysotile-mediated toxicity to the rat alveolar macrophages.

In order to examine the pulmonary toxicity of kerosene oil and its combustion product (soot) in asbestos-exposed rats, various biochemical and chemical parameters were assayed. Treatment of rats with a single intratracheal dose of chrysotile asbestos (5 mg) and kerosene (50 microliters) or its soot (5 mg) in combination led to an increased number of pulmonary alveolar macrophages (PAM), elevated levels of hydrogen peroxide, and thiobarbituric acid-reacting substances, alterations in the activities of primary (glutathione peroxidase and catalase) and secondary (glutathione reductase and glucose-6-phosphate dehydrogenase) endogenous antioxidant enzymes, and depletion in the levels of glutathione in PAM compared to the chrysotile, kerosene, or soot alone. These changes may indicate the generation of oxidative stress in the macrophages. The resulting oxidative stress may be subsequently critical in collapsing the cellular membrane, which may change the cell membrane permeability and may also damage the phagolysosomal membrane, thereby releasing the membrane bound enzymes as indicated by an increased leakage of intracellular acid phosphatase and lactate dehydrogenase. The injury to macrophages may trigger events that lead to lung fibrosis and/or malignancies in the exposed animals. This study may be helpful in understanding the etiology of certain clinical and pathological disorders in the population exposed simultaneously to both asbestos and kerosene or its combustion products.

Animals↗
PubMed1997

Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins.

Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides.

Animals↗
PubMed1996

Chrysotile inhibits glutathione-dependent protection against the onset of lipid peroxidation in rat lung microsomes.

The glutathione and vitamin E dependent protection of lipid peroxidation in an NADPH (0.4 mM) and chrysotile (500 micrograms/ml) containing system were investigated in vitro in rat lung microsomes. Addition of 1 mM glutathione to the above reaction system containing microsomes supplemented with vitamin E (1 nmol/mg protein) reduced lipid peroxidation. Similar protection by glutathione could be observed in normal unsupplemented microsomes though the degree of protection was less pronounced. Addition of free radical scavengers such as, superoxide dismutase (100 units/ml), catalase (150 units/ml), mannitol (1 mM) and beta-carotene (0.5 mM) to the reaction system showed an insignificant effect on lipid peroxidation. When the reaction was carried out in absence of glutathione, vitamin E content of peroxidizing microsomes decreased rapidly. In this system a concomitant increase in the activity of microsomal glutathione-S-transferase was observed which may serve as an alternative pathway to detoxify lipid peroxides. Addition of glutathione alone to the reaction system prevented both against the loss in vitamin E content and increase in the activity of glutathione-S-transferase. Supplementation of both vitamin E and glutathione was found to be effective in lowering glutathione-S-transferase activity to that of normal basal level. Our results suggest that chrysotile-mediated stimulation of NADPH-dependent lipid peroxidation may be due to hampering of glutathione-dependent protection which may ultimately exhaust membrane bound vitamin E. Our data further suggest that the lung tissue may have an inbuilt mechanism whereby glutathione-S-transferase may be triggered to cope with the excessive production of lipid peroxides.

Animals↗
PubMed1995

Augmentation of chrysotile-induced oxidative stress by BHA in mice lungs.

Asbestos is known to induce oxidative stress in the lung. The consumption of butylated hydroxyanisole (BHA) in preserved food and soft drinks is increasing in the general population, which includes workers in asbestos factories. Because there is no information on the effect of co-exposure to chrysotile and BHA, the time-dependent effects of a single intratracheal dose of chrysotile (1 mg per mouse) and a single ip dose of BHA (350 mg/kg body weight) on various indices of oxidative stress such as lipid peroxidation, hydrogen peroxide generation, glutathione peroxidase (GPX), glutathione reductase (GR), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione (GSH) were followed for up to 14 days. Microsomal lipid peroxidation (as well as that induced by NADPH) was significantly enhanced by BHA in the chrysotile-exposed group. GPX and GR activities in the same group were gradually decreased by BHA. Non-significant modulation of catalase activity by BHA was also noted. BHA induces GSH to a significant extent in lungs exposed with chrysotile. An increase in the G6PDH activity was maximal (19%; P < 0.05) at day 3. The results clearly demonstrate that BHA enhances chrysotile-induced oxidative stress in the lung.

Animals↗
PubMed1994

Differential role of hydrogen peroxide and organic peroxides in augmenting asbestos-mediated DNA damage: implications for asbestos induced carcinogenesis.

The incubation of asbestos with DNA in presence of peroxides augmented DNA damage several fold as compared to the damage caused by individual treatments. Asbestos in presence of hydrogen peroxide causes DNA double strand breaks, damage to its deoxyribose sugar moiety and enhanced DNA fidelity. However, only DNA double strand breaks and enhanced DNA fidelity could be recorded in presence of organic hydroperoxide/peroxide but no DNA sugar damage could be observed. Further, the extent of DNA damage could be correlated to the carcinogenic potential of asbestos fibre. Crocidolite, the most carcinogenic variety of asbestos, produces maximum damage to DNA in presence of both hydrogen peroxide and organic hydroperoxide/peroxide while chrysolite which is only a co-carcinogen produces significantly less DNA damage. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxide/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced respectively from these inorganic and organic peroxides.

Animals↗
PubMed1994

Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system.

This article reports the effect of coexposure to Indian chrysotile asbestos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug-metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 days after a single intratracheal inoculation. Exposure to soot resulted in a significant induction of the pulmonary microsomal cytochrome P450 and the activity of dependent monooxygenase, benzo(a)pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induced at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cytochrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial stages, while all these parameters except GST were induced at later stages. However, coexposure to chrysotile and soot led to a significant inhibition in the cytochrome P450 levels, activities of B[a]P hydroxylase, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hydroxylase, and epoxide hydrase but a decrease in GST was observed. These results clearly show that the intratracheal coexposure to high levels of asbestos and kerosene soot alters the metabolic activity of the lung, which is turn may retain toxins in the system for a longer period, resulting in adverse pathological disorders.

Animals↗
PubMed1993

Modulation of macrophage-mediated cytotoxicity by kerosene soot: possible role of reactive oxygen species.

The involvement of reactive oxygen species (ROS) in the cytotoxicity of soot on rat alveolar macrophages has been postulated. A single intratracheal injection of soot (5 mg) in corn oil significantly induced the macrophage population, hydrogen peroxide (H2O2) generation, thiobarbituric acid (TBA)-reactive substances of lipid peroxidation, and the activities of extracellular acid phosphatase (AP) and lactate dehydrogenase (LDH) at 1, 4, 8, and 16 days of postinoculation. The activities of glutathione peroxidase (GPX) and catalase (CAT) were significantly inhibited at all the stages, while glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) showed a different pattern. These results show that soot is cytotoxic to alveolar macrophages and suggest that ROS may play a primary role in the cytotoxic process.

Animals↗
PubMed1993

Cytotoxic and genotoxic effects of calcium silicates on human lymphocytes in vitro.

Calcium silicate has been considered as a possible replacement for asbestos due to its heat and fire resistance. We describe the cytotoxic and genotoxic potential of calcium silicate using peripheral human blood lymphocytes. Calcium silicates at concentrations of 10 and 100 micrograms/ml significantly increased the frequencies of chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs). The increases in CAs and SCEs were dose-dependent, though not linearly. A significant decrease in the proliferation rate index was observed with increased dose of calcium silicates. The induction of chromatid-type aberrations indicates that the clastogenic activity of calcium silicate is S-phase-dependent.

Adult↗
PubMed1993

Asbestos induced oxidative injury to DNA.

DNA-damaging effects of asbestos in the presence of organic peroxides and hydroperoxides were investigated. The destabilization of the secondary structure of DNA, damage to deoxyribose sugar and DNA fidelity were measured, respectively, by S-1 nuclease hydrolysis, the formation of thiobarbituric acid (TBA)-reacting species and a melting temperature (Tm) profile using calf thymus DNA. S-1 nuclease hydrolysis and Tm determinations have shown that the presence of benzoylperoxide (BOOB), cumene hydroperoxide (COOH) or tertiary-butyl hydroperoxide (t-BOOH) increased asbestos-mediated DNA damage by a large factor compared either to asbestos alone or to peroxide or hydroperoxide alone. However, no formation of TBA-reacting species could be observed in this system. The quenchers of reactive oxygen species (ROS) afforded protection against DNA damage. These results suggest that asbestos in the presence of organic peroxides and hydroperoxides damage the DNA which is mediated by the generation of oxygen free radicals. The significance of these results in relation to the development of cancer of the respiratory tract among the asbestos exposed population is discussed.

Animals↗
PubMed1992

Induction of chromosomal aberrations in bone marrow cells of asbestotic rats.

In the present study, cytogenetic effects of Indian chrysotile asbestos in rat bone marrow cells after 290 days of intratracheal inoculation (5 mg dust/0.5 ml normal saline), when it develops massive pulmonary fibrosis, were investigated. The pulmonary fibrosis was confirmed by both histopathological studies and increased collagen content in the lung of the treated animals. In the asbestotic rats a significant increase in chromosomal aberrations was recorded and a decrease in mitotic index of bone marrow cells. The types of chromosomal aberrations in these cells were chromatid gaps and breaks. The results indicate the significant cytogenetic changes in the bone marrow cells of asbestotic rats and also suggest that these changes directly or indirectly may be one of the biological events involved in eliciting the asbestos-mediated toxic responses.

Animals↗
PubMed1992

Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs.

In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal co-exposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.

Animals↗
PubMed1991

The effect of thyroxine on small intestinal motility in the elderly.

OBJECTIVE: To study the effects of thyroxine on orocaecal transit time in a group of elderly hypothyroid patients on long-term thyroxine replacement therapy. DESIGN: Measurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time. PATIENTS: Fifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60-94 years (median 78 years) receiving initially 50-200 micrograms of oral thyroxine daily (median 100 micrograms). MEASUREMENTS: Serum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy. RESULTS: On withdrawal of therapy, the median transit time increased from 75.0 to 135 minutes (P less than 0.01), the median TSH increased from 1.8 to 2.3 mU/l (P = NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P less than 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P = NS), the median TSH decreased to 1.1 mU/l (P = NS) and the median FT4 increased to 14.1 pmol/l (P less than 0.01). CONCLUSIONS: These findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.

Aged↗
PubMed1991

Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types.

Adult↗