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.

The hepatic handling of sulfobromphthalein in aging Fischer-344 rats: in vivo and in vitro studies

1985 ◽  
Vol 4 (1) ◽  
pp. 73-85 ◽  
Author(s):  
S. Kanai ◽  
K. Kitani ◽  
S. Fujita ◽  
H. Kitagawa
Keyword(s):  
In Vitro Studies ◽  
Fischer 344 Rats ◽  
Fischer 344

IN VITRO ANESTHETIC DEPLUORINATION AND IN VIVO LIVER FUNCTION IN FISCHER 344 RATS WITH CHRONIC RENAL FAILURE

1980 ◽  
Vol 53 (3 Suppl) ◽  
pp. S253-S253 ◽  
Author(s):  
S. A. Rice ◽  
T. S. Sievenpiper ◽  
R. I. Mazze
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Liver Function ◽  
Fischer 344 Rats ◽  
Fischer 344

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

Cold- and norepinephrine-induced thermogenesis in younger and older Fischer 344 rats

1988 ◽  
Vol 254 (3) ◽  
pp. R457-R462 ◽  
Author(s):  
R. B. McDonald ◽  
B. A. Horwitz ◽  
J. S. Hamilton ◽  
J. S. Stern
Keyword(s):  
Body Mass ◽  
Mitochondrial Protein ◽  
Brown Fat ◽  
O2 Consumption ◽  
Fischer 344 Rats ◽  
Nonshivering Thermogenesis ◽  
Fischer 344 ◽  
Isolated Mitochondria

Older rats exposed to low environmental temperatures show attenuated thermogenesis. However, the mechanisms responsible for this attenuation are not clear. This investigation evaluated the possibility that reduced nonshivering thermogenic capacity is associated with this attenuation. O2 consumption was measured in male Fischer 344 rats ages 7 and 24 mo at thermoneutrality (26 degrees C), during exposure to cold (6 degrees C) for 2 h, and during norepinephrine (NE) infusion (an in vivo measure of nonshivering thermogenesis). In addition, the binding of GDP to isolated mitochondria of brown fat, an in vitro estimate of nonshivering thermogenesis, was also measured. Resting mass-independent O2 consumption (ml.min-1.g body mass -0.67) was not different between the two age groups. However, mass-independent O2 consumption was significantly greater in the younger vs. older rats during 2 h of cold exposure (younger, 2.86 +/- 0.19 l/kg body mass 0.67; older, 2.39 +/- 0.10 l/kg body mass 0.67) and during 20 min of maximum NE infusion (younger, 410.4 +/- 15.1 ml/kg body mass)] was greater in younger than ml/kg body mass 0.67). Brown fat mass [absolute (g) as well as relative (g tissue/kg body mass)] was greater in younger than in older rats. Furthermore, younger rats had significantly greater binding of GDP to isolated mitochondria of brown fat than did the older rats. This effect was true whether the data were expressed as nanomoles bound per milligram mitochondrial protein (32% lower in older rats), bound nanomoles recovered (57% lower), or bound picogram per kilogram body mass 0.67 (59% lower).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius

1995 ◽  
Vol 268 (2) ◽  
pp. R487-R491 ◽  
Author(s):  
S. Ma ◽  
F. M. Abboud ◽  
R. B. Felder
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Nucleus Tractus Solitarius ◽  
Discharge Rate ◽  
Brain Slices ◽  
Spontaneous Discharge ◽  
Fischer 344 Rats ◽  
Fischer 344

The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L-arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control.

MST3 is involved in ENaC-mediated hypertension

2019 ◽  
Vol 317 (1) ◽  
pp. F30-F42
Author(s):  
Te-Jung Lu ◽  
Wei-Chih Kan ◽  
Sung-Sen Yang ◽  
Si-Tse Jiang ◽  
Sheng-Nan Wu ◽  
...  
Keyword(s):  
Kidney Cells ◽  
Hypertensive Rats ◽  
Madin Darby Canine Kidney ◽  
Spontaneously Hypertensive ◽  
Hypomorphic Mutation ◽  
And Oxidative Stress ◽  
Darby Canine Kidney ◽  
Canine Kidney

Liddle syndrome is an inherited form of human hypertension caused by increasing epithelial Na+ channel (ENaC) expression. Increased Na+ retention through ENaC with subsequent volume expansion causes hypertension. In addition to ENaC, the Na+-K+-Cl− cotransporter (NKCC) and Na+-Cl− symporter (NCC) are responsible for Na+ reabsorption in the kidneys. Several Na+ transporters are evolutionarily regulated by the Ste20 kinase family. Ste20-related proline/alanine-rich kinase and oxidative stress-responsive kinase-1 phosphorylate downstream NKCC2 and NCC to maintain Na+ and blood pressure (BP) homeostasis. Mammalian Ste20 kinase 3 (MST3) is another member of the Ste20 family. We previously reported that reduced MST3 levels were found in the kidneys in spontaneously hypertensive rats and that MST3 was involved in Na+ regulation. To determine whether MST3 is involved in BP stability through Na+ regulation, we generated a MST3 hypomorphic mutation and designated MST3+/− and MST3−/− mice to examine BP and serum Na+ and K+ concentrations. MST3−/− mice exhibited hypernatremia, hypokalemia, and hypertension. The increased ENaC in the kidney played roles in hypernatremia. The reabsorption of more Na+ promoted more K+ secretion in the kidney and caused hypokalemia. The hypernatremia and hypokalemia in MST3−/− mice were significantly reversed by the ENaC inhibitor amiloride, indicating that MST3−/− mice reabsorbed more Na+ through ENaC. Furthermore, Madin-Darby canine kidney cells stably expressing kinase-dead MST3 displayed elevated ENaC currents. Both the in vivo and in vitro results indicated that MST3 maintained Na+ homeostasis through ENaC regulation. We are the first to report that MST3 maintains BP stability through ENaC regulation.

scholarly journals Protective Effect of Hydroxytyrosol Against Oxidative Stress Induced by the Ochratoxin in Kidney Cells: in vitro and in vivo Study

2020 ◽  
Vol 7 ◽  
Author(s):  
Rosalia Crupi ◽  
Ernesto Palma ◽  
Rosalba Siracusa ◽  
Roberta Fusco ◽  
Enrico Gugliandolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
In Vivo Study ◽  
Kidney Cells

Age-related increases in diaphragmatic maximal shortening velocity

1996 ◽  
Vol 80 (2) ◽  
pp. 445-451 ◽  
Author(s):  
S. K. Powers ◽  
D. Criswell ◽  
R. A. Herb ◽  
H. Demirel ◽  
S. Dodd
Keyword(s):  
Force Production ◽  
Specific Force ◽  
Fischer 344 Rats ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
Fischer 344 ◽  
Age Related ◽  
Highly Correlated ◽  
Related Increase

Recent evidence demonstrates that aging results in an increase in fast (type IIB) myosin heavy chain (MHC) in the rat diaphragm. It is unknown whether this age-related change in fast MHC influences the diaphragmatic maximal shortening velocity (Vmax). Therefore, we tested the hypothesis that aging is associated with an increase in the diaphragmatic Vmax and that the increase in the Vmax is highly correlated with the percentage of type IIb MHC. In vitro contractile properties were measured with costal diaphragm strips obtained from young (4 mo old; n = 8) and (old 24 mo old; n = 8) male Fischer-344 rats. Diaphragmatic maximal tetanic specific force production was 14.5% lower in the old compared with the young animals (23.0 +/- 0.4 vs. 19.7 +/- 0.8 N/cm2; P < 0.05). In contrast, the diaphragmatic Vmax was significantly higher in the old compared with the young animals (5.5 +/- 0.1 vs. 4.4 +/- 0.3 lengths/s; P < 0.05). Although the percent type IIb MHC was significantly higher (approximately +14%; P < 0.05) in the old compared with the young animals, the correlation between Vmax and percent type IIb MHC was relatively low (r = 0.50; P = 0.05). These data support the hypothesis that an age-related increase in diaphragmatic Vmax occurs; however, factors in addition to type IIb MHC are involved in regulating diaphragmatic Vmax. Interestingly, although aging resulted in a decrease in diaphragmatic maximal specific force production, power output at all muscle loads was maintained in the old animals due to the increase in diaphragmatic shortening velocity.

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