scholarly journals Nephrotoxic Potential of the Three Dichlorobenzene Isomers in Isolated Kidney Cells from Male Fischer 344 Rats

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Gary Rankin ◽  
Alex Torres ◽  
Carley Carter ◽  
David Vidrine ◽  
Amber Sturgill ◽  
...  
Keyword(s):  
Kidney Cells ◽  
Fischer 344 Rats ◽  
Isolated Kidney ◽  
Fischer 344

scholarly journals Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats

2020 ◽  
Vol 22 (1) ◽  
pp. 292
Author(s):  
Gary O. Rankin ◽  
Christopher R. Racine ◽  
Monica A. Valentovic ◽  
Dianne K. Anestis
Keyword(s):  
Reactive Metabolites ◽  
Kidney Cells ◽  
Fischer 344 Rats ◽  
Isolated Kidney ◽  
Renal Metabolism ◽  
Fischer 344 ◽  
Primary Mechanism ◽  
Toxic Metabolites

The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0–1.5 mM; up to 90 min) or vehicle. Of these metabolites, 3,5-DCPHA was the most potent nephrotoxicant, with 3,5-DCNB intermediate in nephrotoxic potential. 2-A-4,6-DCP and 3,5-DCAA were not cytotoxic. In separate experiments, 3,5-DCNB cytotoxicity was reduced by pretreating IKC with antioxidants and cytochrome P450, flavin monooxygenase and peroxidase inhibitors, while 3,5-DCPHA cytotoxicity was attenuated by two nucleophilic antioxidants (glutathione and N-acetyl-L-cysteine). Incubation of IKC with 3,5-DCA (0.5–1.0 mM, 90 min) produced only 3,5-DCAA and 3,5-DCNB as detectable metabolites. These data suggest that 3,5-DCNB and 3,5-DCPHA are potential nephrotoxic metabolites and may contribute to 3,5-DCA induced nephrotoxicity in vivo. In addition, the kidney can bioactivate 3,5-DCNB to toxic metabolites, and 3,5-DCPHA appears to generate reactive metabolites to contribute to 3,5-DCA nephrotoxicity. In vitro, N-oxidation of 3,5-DCA appears to be the primary mechanism of bioactivation of 3,5-DCA to nephrotoxic metabolites.

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

Ultrastructure of rat alveolar macrophages activated in situ by poly:IC

1987 ◽  
Vol 45 ◽  
pp. 768-769
Author(s):  
A. M. Klinkner ◽  
R. A. Weiss ◽  
A. Kelley ◽  
P. J. Bugelski
Keyword(s):  
Venous Blood ◽  
Intratracheal Instillation ◽  
Buffy Coat ◽  
Fischer 344 Rats ◽  
Blood Monocytes ◽  
Fischer 344 ◽  
Polyinosinic:Polycytidylic Acid ◽  
Macrophage Activator ◽  
Endogenous Peroxidase

Polyinosinic:polycytidylic acid is an inducer of interferon and a macrophage activator. We have found that intratracheal instillation of polyI:C (IT-pI:C) activates rat bronchoalveolar lavage cells (BAL) for a variety of functions. Examination of Giemsa stained, cytocentrifuge preparations showed that IT-pI:C induced a population of BAL not seen in resident BAL. The morphology of these cells suggested that they might be derived from blood monocytes. To test this hypothesis we have examined several populations of macrophages that had been stained for endogenous peroxidase activity as a marker of cells derived from the monocyte-macrophage lineage.Macrophages were obtained from Fischer 344 rats. Peritoneal exudate cells (PEC) were collected by lavage 4 days after i.p. injection of 20 ml 3% thioglycolate. Buffy coat monocytes were separated from venous blood from naive rats.

Antagonism by Progesterone of Diethylstilbestrol-lnduced Pituitary Tumorigenesis in Fischer 344 Rats: Effects on Sex Steroid Receptors and Tyrosine Hydroxylase mRNA

1996 ◽  
Vol 63 (6) ◽  
pp. 530-539 ◽  
Author(s):  
Gerardo G. Piroli ◽  
Claudia A. Grillo ◽  
Monica G. Ferrini ◽  
Victoria Lux-Lantos ◽  
Alejandro F. De Nicola
Keyword(s):  
Tyrosine Hydroxylase ◽  
Steroid Receptors ◽  
Sex Steroid ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Sex Steroid Receptors ◽  
Pituitary Tumorigenesis

scholarly journals Effect of methyl isocyanate (MIC) gas on the eyes of Fischer 344 rats.

1987 ◽  
Vol 72 ◽  
pp. 105-108 ◽  
Author(s):  
B N Gupta ◽  
S A Stefanski ◽  
J R Bucher ◽  
L B Hall
Keyword(s):  
Methyl Isocyanate ◽  
Fischer 344 Rats ◽  
Fischer 344

The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats

2007 ◽  
Vol 27 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Shankai Yin ◽  
Zhiping Yu ◽  
Ravi Sockalingam ◽  
Manohar Bance ◽  
Genlou Sun ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Large Deletion ◽  
Fischer 344 Rats ◽  
Fischer 344
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