R.K.S. Dogra

Styrene-induced immunomodulation in mice

Male mice given different oral doses (0.05, 0.03 or 0.02 x LD50/animal/day) of styrene (LD50 = 1 g/kg) daily for 5 days did not incite any overt toxicity in lymphoid organs or on hematologic parameters. At the tested dose levels styrene produced a mild reduction in the organ weight of adrenal and spleen and slight reduction in the cellular viability of lymph nodes. There was a dose-dependent suppression in the humoral immune response (IgM-producing PFCs of spleen and serum anti-SRBC HA titre) to SRBC. The proliferative response to the B-cell mitogen, LPS however revealed a significant increase in the incorporation of 3HT with middle and lowest doses of styrene. The results of cell-mediated immunity appeared somewhat unexpected and more complex as exposure resulted in a dose-dependent enhancement in the cutaneous DTH reaction to SRBC together with increased blastogenic response of splenic lymphocytes to phytohaemagglutinin (PHA). Additionally, there was significant impairment in the functional activity (NBT reduction, attachment and phagocytic indices) of nonadherent and adherent peritoneal exudate cells. Based on the present data the study identifies the immunotoxic potential of styrene and which acts differently on various arms of the rodents immune system.

Experimental infective manganese pneumoconiosis in guinea pigs

Abstract In order to study the role of an infective factor in the course of manganese pneumoconiosis, guinea pigs were intratracheally inoculated only with Candida albicans, a common commensal of upper respiratory tract of miners, manganese dioxide alone or with the combination of C. albicans and manganese dioxide dust. The histopathological studies revealed that at the termination of the experiment (180 days) the combined effect of dust and organism produced thick reticulin and collagen fibrosis in the lungs, manganese dioxide alone produced fibrotic reaction comprised of only thick reticulin fibers while the organisms alone produced slight lymphoid hyperplasia and no fibrosis.

Wood dust toxicity:In vivo andin vitro studies

Abstract The relationship between in vitro cytotoxicity, hemolytic activity, and in vivo fibrogenicity of wood dusts. Dalbergia sissoo (Sheesham) and Mangifera indica (Mango), were examined. It was observed that hemolytic activity may be indicative of the degree of acute toxicity and macrophage cytotoxicity of the fibrogenicity of the dusts. It has been suggested that these two parameters may be useful for assessing a wood dust for its acute toxicity and fibrogenicity.

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.

Experimental infective pneumoconiosis: effect of asbestos dust and Candida albicans infection on the lungs of rhesus monkeys.

Abstract The combined effect of Candida albicans, a facultative pathogen in the normal physiological condition in the throat of miners, and amosite dust produces after intratracheal inoculation extensive collagenous fibrosis at 330 days in rhesus monkeys. The lesions produced by amosite dust alone comprise fine reticulin fibrosis around bronchioles and blood vessels and moderate interstitial fibrosis. The C. albicans infection alone caused acute inflammatory reaction in the early stages while at the termination of experiment (330 days) the only evidence of pulmonary candidiasis was a few small fibrotic foci of compactly arranged reticulin fibers.

Pathobiochemical response of tracheobronchial lymph nodes following intratracheal instillation of polyvinylchloride dust in rats

PVC dust, following a single intratracheal instillation (25 mg/rat), was substantially cleared through the lymphatic circulation and progressively accumulated in the tracheobronchial lymph nodes (TBLN) in a time-dependent manner for up to 1 year. The tissue response in TBLN during 60–270 days post-instillation of PVC dust was characterized by progressive increase in total organ fresh weight, dry weight, DNA, RNA and protein contents, concurrent with the proliferation of macrophages and hyperplasia of reticular cells. Active phagocytosis and enhanced hydrolytic activity in TBLN was evident around 270 days post-instillation by the appearance of PVC-laden macrophages near and within the dust foci, and increased activity of acid phosphatase, DNAse, RNAse and β-glucuronidase. PVC dust caused degeneration of macrophages, and consequent release of hydrolytic enzymes resulted in limited cytotoxicity without inducing reticulination and fibrosis in the TBLN. The histology and clinical biochemistry of liver, kidney, spleen and serum were not altered and there were no detectable PVC particles in these tissues at up to 365 days. It is therefore concluded that lymphatic clearance of intratracheally instilled PVC dust results in its accumulation and mild foreign body reaction in TBLN which is non-fibrogenic at up to 365 days post-instillation.

Host resistance assays as predictive models in styrene immunomodulation

Three infection models namely an oncogenic virus Encephalomyocarditis (EMCV), a rodent strain of malaria, Plasmodium berghei, and a rodent hookworm parasite, Nippostrongylus brasiliensis, were used to confirm the in vivo immunotoxic potential of styrene reported in our previous communication. The altered host resistance to these challenge infections was evaluated in rodents pre-treated with 0, 0.02, 0.03 or 0.05 x LD50 dose of styrene (5 days/week) for 4 weeks. Significantly increased mortality in mice was observed at the various tested dose levels of styrene when challenged with EMCV. Similarly the results obtained in the malaria infection model indicated increased blood parasitaemia as well as significantly enhanced mortality in styrene-treated animals. Also the rejection of N. brasiliensis was also found to be significantly impaired in animals treated with a higher dose of styrene. These results indicate that the exposure of rodents to styrene can markedly impair host resistance which may have biological significance.

Neutron activation analysis of respirable mica samples and their pathological effects in lungs of rats

Instrumental and radiochemical neutron activation analyses (INAA, RNAA) have been used to quantify the different elements present in mica samples derived from Indian mines and a factory, together with USGS standards using high-resolution gamma-ray spectrometry. Both samples revealed the presence of several toxic elements in appreciable quantities. When tested in a rat model system over a period of 360 days after intratracheal injection of mica samples of respirable size (50 mg/animal), the animals which received the factory sample containing shellac exhibited enhanced dust-induced pulmonary reaction together with characteristic abscess formation at later periods. The significance of these findings is discussed.