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

Abstract

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.

Kerosene: A Review of Household Uses and their Hazards in Low- and Middle-Income Countries

“…Arif et al (1994) reported that rats given a single intratracheal dose of kerosene soot (5 mg) and chrysotile asbestos (5 mg) showed inhibition of drug-metabolizing enzymes critical in the clearance mechanism of the lung. The joint effect was greater than that measured for exposures to soot or asbestos alone.…”

Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

“…For a decade, several investigators hypothesized that the process of disease development due to asbestos exposure in humans as well as in animals may be enhanced due to coexposure to poly aromatic hydrocarbons (PAHs) [5,6]. Moreover, the continuous derangement in the pulmonary drug metabolizing enzymes by asbestos affects the metabolism and clearance of a variety of environmental pollutants reaching the lung [7]. Earlier studies from our laboratory have suggested that chrysotile, a carcinogenic variety of asbestos, alters the activities of phase I and phase II drug metabolizing enzymes [8].…”

Effect of Kerosene and Its Soot on the Chrysotile-Mediated Toxicity to the Rat Alveolar Macrophages

“…Epidemiological and experimental studies clearly indicated a multiplicative effect of asbestos and cigarette smoke on the initiation of bronchogenic carcinoma (Selikoff et al, 1980). Besides smoking, several other factors including kerosene oil can also influence the process of disease development in asbestos-exposed subjects (Arif et al, 1992(Arif et al, , 1994.…”

“…The mechanism of soot toxicity is not fully understood at present; however, in a recent report we have shown that soot particles can cause cytotoxicity to the rat pulmonary alveolar macrophages, and reactive oxygen metabolites could play a primary role in the cytotoxic process . While large number of studies have been conducted on asbestos and cigarette smoke, only a few reports are available on the combined effect of asbestos and kerosene/soot on pulmonary system (Arif et al, 1992(Arif et al, , 1994). …”