Anand P. Sahu

Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

Genotoxic effects of arsenic: Prevention by functional food-jaggery

Arsenic contamination in groundwater is global human health hazard. There is no effective remedial action of chronic arsenicosis, however, a well-nourished diet can modulate the onset of adverse health effects and the delayed effect of arsenic in drinking water. In the present work, genotoxic effects induced by arsenic through parenteral administration and ameliorate by jaggery. Chromosomal aberrations were more pronounced in arsenic treated mice, while supplementation of jaggery with arsenic reduced the incidence of the aberrations. The outcome of study showed that Jaggery the natural functional food has the efficiency to encounter the genotoxic effects induced by arsenic.

Proinflammatory and Anti-Inflammatory Cytokine Balance in Gasoline Exhaust Induced Pulmonary Injury in Mice

Proinflammatory and anti-inflammatory cytokine balance and associated changes in pulmonary bronchoalveolar lavage fluid (BALF) of unleaded gasoline exhaust (GE) exposed mice were investigated. Animals were exposed to GE (1 L/min of GE mixed with 14 L/min of compressed air) using a flow-past, nose-only, dynamic inhalation exposure chamber for different durations (7, 14, and 21 days). The particulate content of the GE was found to be 0.635, ± 0.10 mg PM/m3. Elevated levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were observed in BALF of GE-exposed mice, but interleukin 1wβ (IL-1β) and the anti-inflammatory cytokine interleukin-10 (IL-10) remained unaffected. GE induced higher activities of alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), and lactate dehydrogenase (LDH) in the BALF, indicating Type II alveolar epithelial cell injury, Clara-cell injury, and general toxicity, respectively. Total protein in the BALF increased after 14 and 21 days of exposure, indicating enhanced alveolar-capillary permeability. However, the difference in the mean was found statistically insignificant in comparison to the compressed air control. Total cell count in the BALF of GE-exposed mice ranged between 0.898 and 0.813 × 106 cells/ml, whereas the compressed air control showed 0.65 × 106 cells/mL. The histopathological changes in GE-exposed lung includes perivascular, and peribronchiolar cuffing of mononuclear cells, migration of polymorphonuclear cells in the alveolar septa, alveolar thickening, and mild alveolar edematous changes indicating inflammation. The shift in pro- and anti-inflammatory cytokine balance and elevation of the pulmonary marker enzymes indicate toxic insult of GE. This study will help in our understanding of the mechanism of pulmonary injury by GE in the light of cytokine profiles, pulmonary marker enzymes, and lung architecture.

Effect of intratracheal injection of mica dust on the lymph nodes of guinea pigs

Histopathological changes in the tracheo-bronchial lymph nodes were studied up to 365 days in guinea pigs following intratracheal injection of a suspension of mica dust. In general, the cytotoxic effect provoked by dust was not pronounced as the majority of the swollen dust-laden macrophages retained their normal structure at the termination of the experiment and fibrotic lesions were limited to the formation of thick reticulin fibers. The poor fibrogenic response of mica dust has been attributed to its low cytotoxicity.

Fibrogenic response in murine lungs to asbestos.

Pulmonary fibrogenic response was investigated in mice following intratracheal inoculation of amosite, anthophylite and tremolite varieties of Indian asbestos and studies were made over a period of 150 days. At early periods all the varieties produced acute inflammatory reaction in the lungs. Thick reticulum fibers were encountered at later periods with amosite, while only thin reticulum fibers developed with anthophyllite or tremolite variety. The formation of asbestos bodies did not take place with any of the asbestos varieties even at 150 days. The deviation in the pulmonary fibrogenic response in mice has been attributed to species difference.

Effect of quartz dust on the lungs of mice

Intratracheal inoculations of quartz dust (250 mg/kg body weight) of a particle size less than 5 mum were given in mice and pulmonary tissue reactions studied over a period of 210 days. Acute inflammatory reaction in the lung parenchyma was observed at early periods and later the aggregates of dust laden macrophages encountered around bronchi and blood vessels. Towards the termination of the experiment at 210 days the fibrotic reaction comprised chiefly of thick compactly arranged reticulin fibers with few collagen fibers which remained restricted to the peribronchial and perivascular areas. There was no silicotic nodule formation in the parenchyma of the lung. The atypical pulmonary tissue response to quartz dust in mice has been attributed to different tissue reactivity.

Pulmonary response to kaolin, mica and talc in mice

Following intratracheal inoculation the pulmonary fibrogenic response of kaolin, mica and talc was investigated in mice over a period of 210 days. All the three dusts incited acute inflammatory reaction at early periods but with mica dust the acute reaction persisted longer. Subsequently there was gradual increase in the fibroblastic activity in the focal areas and mica produced, in addition, many cholesterol cleft-like structures together with marked fibroblastic activity and lymphocytic infiltration. Towards the termination of experiment at 210 days the fibrosis, in general, remained restricted to grade II with kaolin and mica while talc produced thickened interalveolar septa. The transport of dust from lungs to lymph nodes occurred earlier with mica than with kaolin or talc dust accompanied with little fibrotic reaction. The significance of the findings has been discussed.

Experimental manganese lymphadenopathy in guinea pigs.

Experimental manganese lymphadenopathy was produced in guinea pigs by intratracheal inoculation of manganese dioxide (50 mg/300 g body weight) and histopathologic changes in the tracheobronchial lymph nodes were studied up to 180 days. There was slow extracellular transport of manganese dust into the nodes, which did not provoke any significant reaction at early periods. However, at later periods the nodes exhibited a significant increase in the density of dust particles and the reaction consisted of phagocytosis, degeneration of dust laden macrophages, slight proliferation of fibroblasts, together with some reticulinosis corresponding to deposits of dust particles. The significance of these findings have been discussed from the chronic toxicity viewpoint.ZusammenfassungDurch intratracheale Applikation von Mangandioxid (50 mg/300 g Körpergewicht) wurde bei Meerschweinchen eine experimentelle Lymphadenopathie erzeugt und die histopathologischen Veränderungen in den tracheobronchialen Lymphknoten bis zu 180 Tagen beobachtet. Es wurde ein langsamer extrazellulärer Transport des Manganstaubes in die Lymphknoten gefunden, der in der Anfangsphase zu keinerlei signifikanten Reaktionen führte. In einer späteren Phase zeigten die Lymphknoten jedoch eine signifikante Zunahme in der Verteilungsdichte der Staubpartikel und Reaktionen wie Phagozytose, Degeneration staubbeladener Makrophagen, geringfügige Proliferation von Fibroblasten mit einer der Ablagerung von Staubpartikeln entsprechenden Reticulinose. Die Bedeutung dieser Beobachtungen wird unter dem Gesichtspunkt der chronischen Toxizität diskutiert.

Pleural Lesions Induced by Mineral Dusts, Fibers and Chemicals

Pleural fibrosis (PF), Pulmonary Interstitial Fibrosis (PIF), lung cancer and malignant mesothelioma are well documented changes due to asbestosrelated exposure. PF is increasingly more common than PIF in many asbestos-exposed populations. This was found especially true in populations with less intense exposure (Miller and Miller, 1993). India is a developing country, rapidly industrializing and demand for asbestos and its production has, therefore, greatly increased mainly for construction activity such as cement-asbestos industries. The asbestos exposure, mechanism for the development of disease and prevention needs greater attention to safeguard the exposed workers.

Effect of chronic choline availability on lung and lymph nodes of rat

Male albino rats were given intraperitoneal injections of choline chloride (0. 1,0.33 or 0.5 × lethal dose 50) for a total period of one month and then killed at the end of 30,90 and 240 days for the study of pathotoxicokinetics of choline. Chronic choline administration in rats caused a decrease in growth rate, a dose dependent modulating effect on the somatic tissue indices of lung and lymph nodes, as well as cellularity of lymph nodes. In another experiment, the effect of choline on mica induced pulmonary lesions was studied. The combined effect of choline and mica caused adenocarcinoma of bronchiolar epithelium and marked lymphadenopathy with abnormal cells in the lymph nodes at the termination of experiment (330 days). The results of the present investigation suggest that excess choline availability not only produces pulmonary pathological lesions by itself but it also further enhances the lung lesions in altered pulmonary conditions