Regular articleRenal cysteine conjugate β-lyase-mediated toxicity studied with primary cultures of human proximal tubular cells☆
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Toxicity assessments of selected trichloroethylene and perchloroethylene metabolites in three in vitro human placental models
2022, Reproductive ToxicologyCitation Excerpt :Despite inherent differences in cell lines, the results in this study highlight potential specific vulnerabilities in normal cells to DCVC and/or TCVC insult in the placenta, which is consistent with DCVC and TCVC toxicity in other tissue types such as kidney [6]. It has been well-documented that DCVC [57–60] and TCVC [33,61,62] cause cell-specific toxicity to renal proximal tubular cells because of proximity to circulation, proximal tubular reabsorption and transport, and expression of cysteine conjugate beta-lyase, the enzyme compulsory for DCVC and TCVC bioactivation to reactive metabolites [63,64]. Regarding the placenta, cell-specific vulnerability to DCVC and TCVC is entirely plausible because of high perfusion, mRNA expression [19] and enzymatic activity of cysteine conjugate beta-lyase [24], and metabolic activity [20,65].
Metabolism of Glutathione S-Conjugates: Multiple Pathways
2018, Comprehensive Toxicology: Third EditionIn vitro systems to study nephropharmacology: 2D versus 3D models
2016, European Journal of PharmacologyCitation Excerpt :These new technologies are expected to revolutionize our ability to understand and predict clinically relevant renal responses for their application in kidney disease. To study nephropharmacology the models currently applied include animal models (Gautier et al., 2010) and PTC monolayers (2D) (Chen et al., 1990). Drug testing studies and toxicological screenings use different animal species like mice, rats, hamsters, rabbits, fishes (zebrafish, trout), birds (mainly chicken), guinea pigs, amphibians (xenopus frogs), primates, dogs, cats, etc.
Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene
2013, Toxicology and Applied PharmacologyCitation Excerpt :The nephrotoxicity induced by DCVC is well documented in rats and primary cultures of human kidney cells (Elfarra, 1997; Terracini and Parker, 1965) and has been shown to be mediated through a number of metabolic pathways that result in the formation of reactive electrophiles (Fig. 1). DCVC can be bioactivated by cysteine S-conjugate β-lyases to form chlorothioketene (CTK) and 2-chlorothionoacetyl chloride (2-CTA) (Dekant et al., 1994; Elfarra et al., 1986; Lash and Anders, 1986; Lock and Reed, 2006); two reactive electrophiles (Chen et al., 1990; Elfarra et al., 1987; Lash et al., 1986) that can be hydrolyzed to chloroketene (CK) and 2-chloroacetyl chloride (2-CA). This bioactivation process is widely considered to be primarily responsible for the nephrotoxicity of TCE.
Energy Coupled Na<sup>+</sup> Cotransport
2013, In Vitro Toxicity IndicatorsEnzymes Involved in Processing Glutathione Conjugates
2010, Comprehensive Toxicology, Second Edition
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This work was supported by grants from the American Cancer Society, BC570 (T.W.J.), as well as the National Institutes of Health, AI24179 (A.L.T.), DK38925, and CA48197 (J.L.S.).