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Trichloroaniline effects on renal function in vivo and in vitro
H H Lo1, P I Brown, G O Rankin
1Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Abstract:
Previous studies have demonstrated that mono- and dichloroanilines are capable of inducing acute renal failure in vivo and altering organic ion accumulation by renal cortical slices in vitro. The purpose of this study was to determine the nephrotoxic potential of 4 trichloroaniline (TCA) isomers in vivo and to examine their effects on organic ion accumulation in vitro. In the in vivo experiments, male Fischer-344 rats (4 rats/group) were administered a TCA (0.8 or 1.5 mmol/kg) intraperitoneally (i.p.) or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h. None of the TCA isomers induced marked renal effects at either time point. In vitro, all TCA isomers were effective in decreasing tetraethylammonium and p-aminohippurate accumulation by renal cortical slices at bath concentrations of 10(-3) M with 2,3,4- and 3,4,5-TCA inducing the greatest reductions. These results indicate that TCA can have a direct effect on renal function in vitro, but that the isomers tested are less potent nephrotoxicants than the nephrotoxic mono- and dichloroanilines.
Insights
Trichloroaniline (TCA) isomers did not cause significant kidney damage in rats. However, in lab tests, TCA isomers reduced organic ion uptake in kidney slices, indicating potential direct renal effects.
Area of Science:
- Toxicology
- Nephrology
- Environmental Health
Background:
- Mono- and dichloroanilines are known to cause acute renal failure.
- These compounds also alter organic ion accumulation in kidney tissues.
- Understanding the nephrotoxicity of related compounds is crucial for risk assessment.
Purpose of the Study:
- To evaluate the in vivo nephrotoxic potential of four trichloroaniline (TCA) isomers.
- To investigate the in vitro effects of TCA isomers on organic ion accumulation in renal cortical slices.
Main Methods:
- Male Fischer-344 rats were administered TCA isomers (0.8 or 1.5 mmol/kg) or vehicle intraperitoneally.
- Renal function was monitored at 24 and 48 hours post-administration.
- In vitro experiments assessed the impact of TCA isomers on tetraethylammonium and p-aminohippurate accumulation in renal cortical slices.
Main Results:
- None of the tested TCA isomers induced significant renal effects in vivo at the administered doses.
- In vitro, all TCA isomers reduced organic ion accumulation in renal cortical slices at 10(-3) M.
- 2,3,4-TCA and 3,4,5-TCA demonstrated the most significant reductions in ion accumulation.
Conclusions:
- Trichloroaniline isomers exhibit direct effects on renal function in vitro.
- The tested TCA isomers are less potent nephrotoxicants compared to mono- and dichloroanilines.
- Further research may explore the mechanisms of TCA-induced alterations in renal ion transport.