Immunohistochemical studies on early stage of hepatic damage induced by subacute inhalation of toluene vapor in rats

Abstract

Toluene is one of the most widely used organic solvents and is commonly recognized as a noxious substance inducing chronically toxic damage to neural, hepatic and renal functions in the workers engaged in printing and painting. Although hepatic cells are generally considered to be vulnerable and susceptible to various organic solvents, particularly chloroform and other halogenated hydrocarbons, the hepatotoxic effects of aromatic hydrocarbons including toluene have not yet been sufficiently characterized. In particular, it still seems unclear whether toluene itself can directly act on hepatic cells, inducing toxic damage to their metabolism and function. To assess the toxic effect of toluene inhalation on rat liver, immunohistochemical analyses of the histological markers for hepatic damage were carried out in animals exposed subacutely to toluene vapor. The immunoreactivities of heat shock proteins (HSP-70 and HSP-90) and cytochrome P4502E1 (CYP2E1) in the liver were analyzed to assess the hepatotoxic damage induced by toluene inhalation, and the expression of these histological markers was shown to be substantially enhanced by the subacute exposure to toluene vapor. Toluene inhalation was furthermore shown to enhance the immunoreactivities of alpha-smooth muscle actin (alpha-SMA), collagen, glucocorticoid receptors (GR) and leptin receptors (Ob-R) in the liver. Additional studies using human hepatoma HepG2 cells showed that toluene can directly induce toxic damage to cells. These findings suggest that toluene inhalation may primarily induce hepatic damage, which may be secondarily exacerbated by the activation of systemic processes possibly connected with glucocorticoids and leptin.

Effects of Acute Toluene Toxicity on Different Regions of Rabbit Brain

“…Toluene is also suggested to affect the GABAergic, glutamatergic, serotonergic, and dopaminergic pathways in high doses [10, 11]. Nevertheless, the latest studies indicated that toluene increases the apoptotic activity in the tissue [17, 28]. In this study, Bax and C3 immunoreactivity was reviewed in order to the find out the presence of apoptosis.…”

Chronic intermittent toluene inhalation initiated during adolescence in rats does not alter voluntary consumption of ethanol in adulthood

“…Toluene inhalation can induce hepatotoxicity under various exposure paradigms (Gotohda, Nishimura, & Morita, 2009;Tas et al, 2011), as like ethanol, toluene is metabolized in the liver via the hepatic microsomal system, involving the cytochrome P450 enzymes as well as ADH and ALDH, ultimately being excreted as hippuric acid in the urine (Nakajima et al, 1991). Thus, tolueneinduced hepatic metabolic dysfunction may alter subsequent ethanol consumption and/or the interpretation of ethanol consumption data.…”

Acute cardiotoxic effects of high dose toluene: an experimental study

“…Toluene has been shown to increase apoptotic activity (24)(25)(26). Past studies have demonstrated that Bax and caspase-3 activity increases in liver tissues damaged by organic solvents (12,25,27). El-Nabi Kamel and Shehata et al (28) reported that caspase-3 activity significantly increased in toluene-exposed tissues.…”

“…Although it is reported that damage could occur in the nervous system, liver, kidney, and heart as a result of chronic exposure (10)(11)(12), no explanation has been found for sudden deaths as a result of acute exposure. Some researchers have surmised that deaths could be due to ventricular arrhythmia (13).…”