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In vitro methods of assessing renal damage

L H Lash1

  • 1Department of Pharmacology, Wayne State University, School of Medicine, Detroit, Michigan 48201-1928, USA.

Toxicologic Pathology
|March 21, 1998
PubMed
Summary

Rat kidney proximal tubular and distal tubular cells serve as valuable in vitro models for toxicology. Distal tubular cells show higher sensitivity to oxidative stress, alkylating agents, and oxygen deprivation compared to proximal tubular cells.

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Area of Science:

  • Nephrology
  • Toxicology
  • Cell Biology

Background:

  • Primary cultures of rat kidney cells from specific nephron segments offer in vitro models.
  • These models are useful for studying drug metabolism, membrane transport, and chemical toxicity.
  • Understanding differential cell responses is crucial for toxicological assessments.

Purpose of the Study:

  • To investigate the differential susceptibility of rat proximal tubular (PT) and distal tubular (DT) cells to chemical toxicants.
  • To establish and optimize primary cell cultures for studying short-term and long-term toxicant responses.
  • To evaluate the utility of these cell models in toxicological research.

Main Methods:

  • Isolation of rat renal PT and DT cells via collagenase perfusion and Percoll density-gradient centrifugation.
  • Optimization of serum-free, hormonally defined conditions for primary cell culture.
  • Assessment of cytotoxicity using oxidants, alkylating agents, oxygen deprivation, and ATP depletion agents.

Main Results:

  • Distal tubular (DT) cells were significantly more sensitive to oxidants and alkylating agents targeting soft nucleophiles than proximal tubular (PT) cells.
  • DT cells exhibited greater sensitivity to oxygen deprivation and ATP depletion.
  • Primary cultures maintained differentiated functions and showed similar toxicant susceptibilities as freshly isolated cells, expressing cytochrome P-450 isoforms.

Conclusions:

  • Freshly isolated and primary cultured rat renal PT and DT cells are effective in vitro models for studying chemical toxicity.
  • DT cells display a heightened vulnerability to specific chemical insults and environmental stressors compared to PT cells.
  • These cellular models facilitate the investigation of both acute and chronic toxicological effects of chemicals on kidney cells.

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