Sikandar G. Khan

Protective role of ascorbic acid against asbestos induced toxicity in rat lung: in vitro study.

Asbestos fibers adsorb cytochrome P-450 and P-448 proteins from rat lung micosomal fractions and liberate heme from cytochrome P-448 on prolonged incubation in vitro. further, fibers, decrease the activities of benzo(a)pyrene hydroxylase and glutathione-S-transferase in microsomal and cytosolic fractions respectively. Mineral fibers also stimulate both the enzymatic (NADPH-induced) and non-enzymatic (Fe2(+)-induced) lipid peroxidation in microsomal fractions. Preincubation of microsomal and cytosolic fractions with a physiological concentration of ascorbic acid ameliorates, to a large extent, the changes induced by asbestos fibers.

Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung.

The in vitro and in vivo effect of a carcinogenic variety of asbestos, chrysotile, both on xenobiotic metabolizing enzymes such as benzo[a]pyrene hydroxylase, epoxide hydrolase as well as glutathione-S-transferase activities and microsomal lipid peroxidation in rat lung were examined. The in vitro incubation of chrysotile with microsomes significantly adsorbed heme proteins, cytochrome P-450 and P-448 with the concomitant decrease in the dependent monooxygenase activities. The prolonged incubation of this mineral fibre with microsomes also resulted in the release of heme. It also led to the depletion in the activities of epoxide hydrolase and glutathione-S-transferase. However, it induced lipid peroxidation. When these in vitro effects were validated in vivo, the exposure to early stages produced similar alterations as observed in in vitro studies. However, reverse pattern in the alterations was observed after 90 days of exposure except in the case of lipid peroxidation which remained induced.

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.

Strand breakage in DNA by silicic acid

The alkaline unwinding assay has been used to demonstrate the formation of single-strand breaks in DNA on treatment with silicic acid. Double-stranded DNA, containing no single-strand breaks, when incubated with increasing concentrations of silicic acid, showed the formation of an increasing number of strand breaks per molecule. Experiments on reduction of silicic acid-treated DNA with NaBH4 suggested the possibility of creation of apurinic or apyrimidinic sites. The significance of silicic acid interaction with cellular DNA during asbestos exposure is discussed.

Early biochemical changes in kerosene exposed rat lungs

Abstract The activities of enzymes, which detoxify oxygen free radical species directly or indirectly were studied in lungs of kerosene-treated rats after 1,4,8 and 16 days of exposure. In the kerosene-exposed animals, activities of glutathione peroxidase (GP), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD) and glutathione-s-transferase (GST) were significantly increased; thiobarbituric acid (TBA) - reacting products of lipid peroxidation and reduced glutathione (GSH) content were also significantly increased in the lungs. The increase in reduced glutathione content and elevations in the activities of enzymes and products of lipid peroxidation are suggestive of oxidative stress in the lungs of kerosene exposed animals.

Interaction of mineral fibres with lung cytochrome P-450 system: Impairment of drug metabolizing enzyme activities

Abstract In the present study, in vitro effects of carcinogenic (chrysotile, crocidolite, amosite) and non-carcinogenic (anthophyllite) varieties of asbestos and three varieties of Indian wollastonite (kemolit A-60, Kemolit-N, Kemolit ASB-3) boTh on phase I and phase Ii drug metabolizing enzymes and microsomal lipid peroxidatin (LPO) in rat lung were investigated. All the mineral fibres when incubated with lung microsomes adsorbed cytochrome P-450 to different degrees, while heme was released only by chrysotile and crocidolite. Chrysotile, crocidolite, amosite and kemolit A-60 treatments only led to significant depletion in the activities of benzo(a)pyrene hydroxylase, and epoxide hydratase. The carcinogenic varieties of asbestos also decreased the activity of glutathione-S-transferase, while kemolit-N significantly increased the activity. However, kemolit A-60 and kemolit ASB-3 did not alter the activity of this enzyme. All the dusts which impaired the activities of drug metabolizing enzymes also significantly induced LPO in the microsomes. These data indicate the differential behaviour of asbestos and wollastonite, both on the drug metabolizing enzymes and induction of LPO in rat lung and also suggest that these effects may be related to their toxic potentials.

Concurrent biomineralization of silver ions into Ag0 and AgxO by Leptolyngbya strain JSC-1 and the establishment of its axenic culture

Ionic silver is a potential hazard to aquatic life forms because of the increasing usage of silver based materials. The need for developing a sustainable and ecofriendly process to minimize the toxic effects of the free ions burden is now a scientific consensus. Therefore, we report the latest results in cyanobacterium Leptolyngbya JSC-1 investigating the tolerance towards toxic doses of silver, its extracellular biomineralization and silver nano-deposits formation inside the cells, and speculate about potential environmental impacts. In this study, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) analysis reveal the extracellular biomineralization of soluble silver (1-100u202fμM) into corresponding nanoparticles (50-100u202fnm in diameter) by JSC-1, while X-ray photoelectron spectroscopy (XPS) examination divulged the presence of both Ag+ and Ag0 in extracellularly biomineralized silver, depicting a mixture of both AgxO and elemental Ag. The scanning transmission electron microscopy (STEM), EDS and elemental mapping visualized the formation of intracellular silver nanoparticles. Moreover, this feature of silver tolerance in JSC-1 was further exploited and a novel protocol was developed for isolation and maintenance of axenic culture of this filamentous cyanobacterium. Consequently, this capability of silver biomineralization by JSC-1, both extra- and intra-cellularly might be useful for modeling the Ag resistance mechanism in cyanobacteria and also might be a sustainable alternative for heavy metals bioremediation in aquatic environments.

Augmentation in the Differential Oxidative DNA-Damage by Asbestos in Presence of H2O2 and Organic Peroxide/Hydroperoxide

DNA-damaging effects of asbestos in the presence of hydrogen-peroxide, organic peroxides and hydroperoxides were investigated. The DNA damage was assessed in terms of the destabilization of secondary structure of DNA, damage to deoxyribose sugar and DNA fidelity which were measured respectively by S-1 nuclease hydrolysis, formation of thiobarbituric acid (TBA) — reacting species and melting temperature (Tm) profile using calf thymus DNA. S-1 nuclease hydrolysis and Tm determinations have shown that the presence of hydrogen peroxide (H2O2), benzoyl peroxide (BOOB), Cumene hydroperoxide (COOH) or tertiarybutyl hydroperoxide (t-BOOH) augmented asbestos-mediated DNA damage many folds compared to either asbestos alone or H202/peroxide/hydroperoxide alone. H2O2 also damaged deoxyribose sugar in DNA whereas no formation of TBA-reacting species could be observed in case of any other peroxide/hydroperoxide. The quenchers of reactive oxygen species (ROS) afforded protection against these DNA damage. These results suggest that asbestos in the presence of H2O2/organic peroxides damages DNA which is mediated by the generation of oxygen free radicals. The implications have been made for the significance of these results in relation to the observed development of cancer of respiratory tract among the asbestos-exposed population.

Diminution in Phase I and Phase II Drug Metabolizing Enzymes of Rat Lung by Asbestos: An In Vitro Study

In the present paper studies are presented concerning the effect of three varieties of asbestos namely, chrysotile, crocidolite and amosite, and of titanium dioxide, an inert non-asbestos dust, on the enzymes of phase 1 and phase 2 drug metabolism in isolated rat lung microsomes and post-microsomal fraction. Since 3-methylcholanthrene (3-MC) is known to induce cytochromes P-450 in the IA family and their associated activity, benzo(a)pyrene hydroxylase, therefore, the effect of these mineral fibers on cytochrome P-450 and benzo(a)pyrene hydroxylase in lung microsomes isolated from 3-MC-treated rats was studied.