In vitro nephrotoxicity induced by chloronitrobenzenes in renal cortical slices from Fischer 344 rats.
Chloronitrobenzenes are important chemical intermediates in the manufacture of industrial, agricultural and pharmaceutical agents. Toxicity induced by the various chloronitrobenzene isomers in vivo includes hematotoxicity, immunotoxicity, hepatotoxicity and nephrotoxicity. The purpose of the study was to determine the direct nephrotoxic effects of nitrobenzene and ten chlorinated nitrobenzene derivatives using renal cortical slices as the in vitro model. Renal cortical slices were prepared from kidneys of untreated, male Fischer 344 rats and incubated with nitrobenzene (1.0-5.0 mM), a chloronitrobenzene (0.5-5.0 mM) or vehicle for 2 h. At the end of the 2 h incubation, tissue gluconeogenesis capacity (pyruvate-stimulated gluconeogenesis) and lactate dehydrogenase (LDH) release were determined as measures of cellular function and cytotoxicity. Based on decreased pyruvate-stimulated gluconeogenesis and increased LDH release, the order of decreasing nephrotoxic potential was trichloronitrobenzenes>dichloronitrobenzenes>monochloronitrobenzenes>nitrobenzene. Among the mono- and dichloronitrobenzenes, 1-chloro-3-nitrobenzene and 3,4-dichloronitrobenzene were the most potent nephrotoxicants, while the two trichloronitrobenzenes tested exhibited similar nephrotoxic potentials. These results demonstrate that chloronitrobenzenes are directly nephrotoxic in vitro and that increasing the number of chloro groups increases the nephrotoxic potential of the resulting chloronitrobenzene derivative.
Hong
Suk K
SK
Department of Pharmacology, Joan C. Edwards School of Medicine, Marshall University, 1542 Spring Valley Drive, Huntington, WV 25704-9388, USA.
Anestis
Dianne K
DK
Ball
John G
JG
Valentovic
Monica A
MA
Rankin
Gary O
GO
D000818:Animals; D001711:Biotransformation; D005943:Gluconeogenesis / Q000187:drug effects; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009578:Nitrobenzenes / Q000633:toxicity*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D006843:Hydrocarbons, Chlorinated; D009578:Nitrobenzenes; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase