Tissue lesions kidney damage

The mechanism is believed to involve metabolic activation in the kidney itself. Thus, when radiolabeled chloroform was given to mice, in the kidney, the radiolabel was localized in 

A variety of halogenated alkanes and alkenes such as hexachlorobutadiene, chlorotrifluoro-ethylene, tetrafluoroethylene, and trichloroethylene (Fig. 7.28) are nephrotoxic. Studies have shown that metabolic activation is necessary for toxicity, but this does not involve cytochromes P-450. Thus, hexachlorobutadiene (HCBD) is a potent nephrotoxin in a variety of mammalian species, and the kidney is the major target. 

The compound damages the pars recta portion of the proximal tubule with the loss of the brush border. The result is renal failure detected as glycosuria, proteinuria, loss of concentrating ability, and reduction in the clearance of inulin, p-aminohippuric acid, and tetraethylammonium ion. 

The mechanism seems to involve first the formation of a GSH conjugate in the liver, catalyzed by the microsomal GSH S-transferase. The hepatic metabolite is then secreted into 

An alternative fate for the GSH conjugate is transportation via the blood to the kidney, filtration out of the blood and in the brush border of the tubular cells glutamyltransferase, and cleavage of the conjugate by a dipeptidase to yield the cysteine conjugate. The cysteine conjugate is then taken up by the amino acid transporter system into the proximal tubular cell where toxicity occurs. The result of this is then basically the same as the other scenario. 

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Cardiovascular Effects. Inhalation and oral studies in humans and animals have not revealed any treatment-related histopathological lesions of heart tissue, or impairment of cardiac functions, even at dose levels causing severe liver and kidney damage (Adams et al. 1952 Stewart et al. 1961 Umiker and Pearce 1953). It is possible that high-level carbon tetrachloride exposure may produce cardiac arrhythmias by sensitization of the heart to catecholamines (Reinhardt et al. 1971). Accordingly, there is some concern for cardiovascular toxicity following substantial exposure to carbon tetrachloride. 

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