Bromobenzene nephrotoxicity

Isolated proximal tubules have been utilized to study the mechanisms of nephrotoxicity induced by antibiotics (Sina et al., 1985, 1986), radiocontrast dyes (Humes et al., 1987), metals (Rylander et al., 1985), anoxia (Weinberg, 1985 Weinberg et al., 1987), cellular oxidants (Messana et al., 1988), cysteine conjugates (Rylander et al., 1985 Schnellman et al., 1987 Zhang and Stevens, 1989), and a variety of nephrotoxic bromobenzene metabolites (Schnellman and Mandel, 1986 Schnellman et al., 1987). 

Another example of a glutathione conjugate responsible for toxicity is the industrial chemical hexachlorobutadiene discussed in chapter 7. The diglutathione conjugate of bromobenzene is believed to be involved in the nephrotoxicity after further metabolic activation (chap. 7, Fig. 7.31). 

The nephrotoxicity of bromobenzene (see chap. 7) and possibly 4-aminophenol is also believed to be due to the cysteine conjugates of the quinone or quinoneimine, respectively. Biliary excretion and reabsorption from the gut and delivery to the kidney is a crucial part of this process as it is with hexachlorobutadiene (chap. 7). 

Bromobenzene is also nephrotoxic but because of different mechanisms. This toxicity is due to the production of reactive GSH conjugates. This is discussed in more detail later in this chapter. 

In addition to being hepatotoxic, bromobenzene is also nephrotoxic because of the production of reactive polyphenolic GSH conjugates, covalent binding to protein, and the production of ROS. 2-Bromophenol and 2-bromohydroquinone are both nephrotoxic metabolites of bromobenzene. Quinones are both oxidants and electrophiles, undergoing both one and two electron reduction and reaction with sulfydryl groups such as GSH and... 

Facilitated Accumulation of Nephrotoxicants Bromobenzene, a chemical intermediate, is both a heptotoxicant and a nephrotoxicant. Bromoben-zene-induced nephrotoxicity is characterized by... 

Bromobenzene is also nephrotoxic, possibly due to the production of a reactive metabolite and covalent binding to protein. It has been suggested that the reactive metabolite is formed in the liver and then transported to the kidney. 2-Bromophenol and 2-bromohydroquinone are both nephrotoxic. It seems that the ultimate toxic metabolite is a diglutathionyl conjugate formed from 2-bromohydroquinone (figure 7,14) as this will cause the same lesions in the kidney as bromobenzene, 2-bromophenol and 2-bromohydroquinone when administered to animals. 

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