Trichloroaniline effects on renal function in vivo and in vitro

Lo, Herng-Hsiang; Brown, Patrick I.; Rankin, Gary O.

doi:10.1016/0378-4274(91)90206-l

Cited by 6 publications

(7 citation statements)

References 18 publications

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“…20 In vitro, all of the trichloroaniline isomers reduced organic ion accumulation (p-aminohippurate (PAH) and tetraethylammonium (TEA) ) by renal cortical slices when the trichloroaniline was present in the bath at a concentration of 1 mM.Zo Thus, increasing the number of chloro groups on aniline to three produced derivatives with the ability to directly alter renal function in v i m , but not to induce overt nephrotoxicity in vivo.…”

Section: Introductionmentioning

confidence: 98%

“…Interestingly, when four trichloroaniline isomers (2,3,4-, 2,4,5-, 2,4,6-and 3,4,5-trichloroaniline) were evaluated for nephrotoxic potential in vivo and in vitro, none of the isomers markedly altered renal function in vivo at doses up to 1.5 mmol kg-1. 20 In vitro, all of the trichloroaniline isomers reduced organic ion accumulation (p-aminohippurate (PAH) and tetraethylammonium (TEA) ) by renal cortical slices when the trichloroaniline was present in the bath at a concentration of 1 mM.Zo Thus, increasing the number of chloro groups on aniline to three produced derivatives with the ability to directly alter renal function in v i m , but not to induce overt nephrotoxicity in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat

et al. 1994

J of Applied Toxicology

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Chloroanilines are widely used chemical intermediates for the manufacture of dyes, agricultural chemicals and industrial compounds. Nephrotoxicity occurs as one toxicity following intraperitoneal (i.p.) administration of chloroaniline hydrochlorides to rats. The purpose of this study was to examine the effect of chemical form, route of administration and vehicle on 3,5-dichloroaniline-induced nephrotoxicity. In one set of studies, male Fischer 344 rats (four to eight per group) were administered a single i.p. injection of 3,5-dichloroaniline free base or hydrochloride salt, cysteine hydrochloride or ornithine hydrochloride (0.8, 1.0 or 1.5 mmol kg-1) or an appropriate vehicle and renal function monitored for 48 h. Only 3,5-dichloroaniline hydrochloride induced nephrotoxicity that was characterized as acute renal failure. When 3,5-dichloroaniline free base (0.8 mmol kg-1) was administered in dimethyl sulfoxide (DMSO), all rats died within 24 h. In a second experiment, the free base or hydrochloride form of 3,5-dichloroaniline (1.5 mmol kg-1) or vehicle (0.9% saline or sesame oil, respectively) were administered orally and renal function monitored for 48 h. No evidence of nephrotoxicity was observed following either treatment. However, when the hydrochloride salt was given in 25% DMSO in 0.9% saline, all rats died within 24 h, with two rats demonstrating increased proteinuria, glucosuria and hematuria within the first 6 h after treatment. These results demonstrate that 3,5-dichloroaniline nephrotoxicity is potentiated by the administration of systemic acid, but that acid alone has no effect on renal function at the dose tested. Also, 3,5-dichloroaniline (hydrochloride or free base form) is less toxic orally than when administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat

et al. 1994

J of Applied Toxicology

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“…The formation of mercapturate metabolites from a chloronitrobenzene is considered a biomarker of chloronitrobenzene exposure [20]. While chloroanilines are nephrotoxicants in vivo and in vitro [21,22,23,24,25], it is not clear if these metabolites contribute to chloronitrobenzene nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro

Rankin¹,

Tyree²,

Pope³

et al. 2017

IJMS

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This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15–120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

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“…While the potential adverse health effects of mono- and dichloroanilines have been studied in some detail, little information is available about the toxicity induced by trichloroanilines, including the nephrotoxic potential of trichloroanilines or their mechanisms of inducing nephrotoxicity. Lo et al examined the in vivo and in vitro effects of four trichloroanilines (2,3,4-, 2,4,5-, 2,4,6- and 3,4,5-trichloroaniline) on the renal function of male Fischer 344 rats [ 27 ]. They noted that of the four trichloroanilines tested, 3,4,5-trichloroaniline (TCA) had the greatest nephrotoxic potential in vivo as evidenced by oliguria, increased kidney weight, elevated blood urea nitrogen concentration and altered renal organic ion accumulation.…”

Section: Introductionmentioning

confidence: 99%

“…They noted that of the four trichloroanilines tested, 3,4,5-trichloroaniline (TCA) had the greatest nephrotoxic potential in vivo as evidenced by oliguria, increased kidney weight, elevated blood urea nitrogen concentration and altered renal organic ion accumulation. In vitro , TCA was also the most potent nephrotoxicant of the four trichloroanilines tested, decreasing tetraethylammonium accumulation by renal cortical slices at 1.0 µM concentration [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation

Racine

Ward

Anestis

et al. 2014

IJMS

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Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.

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Trichloroaniline effects on renal function in vivo and in vitro

Cited by 6 publications

References 18 publications

Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat

Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro

3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation

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