The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices

Shana Azri-Meehan, H. P. Mata, A Jay Gandolfi, Klaus Brendel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. Azri-Meehan, S., Mata, H. P., Gandolfi, A. J., and Brendel, K. (1994). Fundam. Appl. Toxicol. 22, 172-177. The interactive toxicity of two nontoxic concentrations of chloroform (CHCI3) and bromotrichloromethane (BrCCI3) was examined in precision-cut rat liver slices. Liver slices were prepared from male Sprague-Dawley rats (220-250 g) pretreated with phenobarbital for 4 days. Toxicants were administered 1 hr apart. Intracellular K+ levels were similar to untreated controls in slices treated with 0.2 mM CHCI3 or 0.1 125 μl (0.25 mg, 1.26 μmol) BrCCI3 alone, indicating that these concentrations were nontoxic. However, addition of both toxicants, irrespective of order, resulted in a time-dependent loss of intracellular K+ which was significant at 9 hr following administration. This was interpreted as evidence of synergistic toxicity. Cytochrome P450 loss was significant as early as 3 hr following exposure to BrCCI3, alone or when added with CHCI3. This loss may be attributed to BrCCI3-induced suicide inactivation of cytochrome P450. Centrilobular hepatocytes may be more susceptible to the interactive toxicity of CHCI3 and BrCCI3. Activity of enzymes found predominantly in this area was significantly decreased in slices exposed to both toxicants relative to controls. Conversely, activity of enzymes found predominantly in the periportal region was similar to that of untreated and treated controls. Interactive toxicity of BrCCI3 and CHCI3 was not a consequence of increased lipid peroxidation or depletion of slice glutathione content. Further studies need to be conducted to elucidate the mechanisms mediating the interactive toxicity of BrCCI3 and CHCI3.

Original languageEnglish (US)
Pages (from-to)172-177
Number of pages6
JournalFundamental and Applied Toxicology
Volume22
Issue number2
DOIs
StatePublished - Feb 1994

Fingerprint

Liver
Toxicity
Rats
Cytochrome P-450 Enzyme System
Bromotrichloromethane
Enzymes
Phenobarbital
Chloroform
Suicide
Lipid Peroxidation
Glutathione
Sprague Dawley Rats
Hepatocytes
Lipids

ASJC Scopus subject areas

  • Toxicology

Cite this

The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. / Azri-Meehan, Shana; Mata, H. P.; Gandolfi, A Jay; Brendel, Klaus.

In: Fundamental and Applied Toxicology, Vol. 22, No. 2, 02.1994, p. 172-177.

Research output: Contribution to journalArticle

Azri-Meehan, Shana ; Mata, H. P. ; Gandolfi, A Jay ; Brendel, Klaus. / The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. In: Fundamental and Applied Toxicology. 1994 ; Vol. 22, No. 2. pp. 172-177.
@article{7aff3857e69c41168777236d6aeb1743,
title = "The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices",
abstract = "The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. Azri-Meehan, S., Mata, H. P., Gandolfi, A. J., and Brendel, K. (1994). Fundam. Appl. Toxicol. 22, 172-177. The interactive toxicity of two nontoxic concentrations of chloroform (CHCI3) and bromotrichloromethane (BrCCI3) was examined in precision-cut rat liver slices. Liver slices were prepared from male Sprague-Dawley rats (220-250 g) pretreated with phenobarbital for 4 days. Toxicants were administered 1 hr apart. Intracellular K+ levels were similar to untreated controls in slices treated with 0.2 mM CHCI3 or 0.1 125 μl (0.25 mg, 1.26 μmol) BrCCI3 alone, indicating that these concentrations were nontoxic. However, addition of both toxicants, irrespective of order, resulted in a time-dependent loss of intracellular K+ which was significant at 9 hr following administration. This was interpreted as evidence of synergistic toxicity. Cytochrome P450 loss was significant as early as 3 hr following exposure to BrCCI3, alone or when added with CHCI3. This loss may be attributed to BrCCI3-induced suicide inactivation of cytochrome P450. Centrilobular hepatocytes may be more susceptible to the interactive toxicity of CHCI3 and BrCCI3. Activity of enzymes found predominantly in this area was significantly decreased in slices exposed to both toxicants relative to controls. Conversely, activity of enzymes found predominantly in the periportal region was similar to that of untreated and treated controls. Interactive toxicity of BrCCI3 and CHCI3 was not a consequence of increased lipid peroxidation or depletion of slice glutathione content. Further studies need to be conducted to elucidate the mechanisms mediating the interactive toxicity of BrCCI3 and CHCI3.",
author = "Shana Azri-Meehan and Mata, {H. P.} and Gandolfi, {A Jay} and Klaus Brendel",
year = "1994",
month = "2",
doi = "10.1006/faat.1994.1021",
language = "English (US)",
volume = "22",
pages = "172--177",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices

AU - Azri-Meehan, Shana

AU - Mata, H. P.

AU - Gandolfi, A Jay

AU - Brendel, Klaus

PY - 1994/2

Y1 - 1994/2

N2 - The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. Azri-Meehan, S., Mata, H. P., Gandolfi, A. J., and Brendel, K. (1994). Fundam. Appl. Toxicol. 22, 172-177. The interactive toxicity of two nontoxic concentrations of chloroform (CHCI3) and bromotrichloromethane (BrCCI3) was examined in precision-cut rat liver slices. Liver slices were prepared from male Sprague-Dawley rats (220-250 g) pretreated with phenobarbital for 4 days. Toxicants were administered 1 hr apart. Intracellular K+ levels were similar to untreated controls in slices treated with 0.2 mM CHCI3 or 0.1 125 μl (0.25 mg, 1.26 μmol) BrCCI3 alone, indicating that these concentrations were nontoxic. However, addition of both toxicants, irrespective of order, resulted in a time-dependent loss of intracellular K+ which was significant at 9 hr following administration. This was interpreted as evidence of synergistic toxicity. Cytochrome P450 loss was significant as early as 3 hr following exposure to BrCCI3, alone or when added with CHCI3. This loss may be attributed to BrCCI3-induced suicide inactivation of cytochrome P450. Centrilobular hepatocytes may be more susceptible to the interactive toxicity of CHCI3 and BrCCI3. Activity of enzymes found predominantly in this area was significantly decreased in slices exposed to both toxicants relative to controls. Conversely, activity of enzymes found predominantly in the periportal region was similar to that of untreated and treated controls. Interactive toxicity of BrCCI3 and CHCI3 was not a consequence of increased lipid peroxidation or depletion of slice glutathione content. Further studies need to be conducted to elucidate the mechanisms mediating the interactive toxicity of BrCCI3 and CHCI3.

AB - The Interactive Toxicity of CHCI3 and BrCCI3 in Precision-Cut Rat Liver Slices. Azri-Meehan, S., Mata, H. P., Gandolfi, A. J., and Brendel, K. (1994). Fundam. Appl. Toxicol. 22, 172-177. The interactive toxicity of two nontoxic concentrations of chloroform (CHCI3) and bromotrichloromethane (BrCCI3) was examined in precision-cut rat liver slices. Liver slices were prepared from male Sprague-Dawley rats (220-250 g) pretreated with phenobarbital for 4 days. Toxicants were administered 1 hr apart. Intracellular K+ levels were similar to untreated controls in slices treated with 0.2 mM CHCI3 or 0.1 125 μl (0.25 mg, 1.26 μmol) BrCCI3 alone, indicating that these concentrations were nontoxic. However, addition of both toxicants, irrespective of order, resulted in a time-dependent loss of intracellular K+ which was significant at 9 hr following administration. This was interpreted as evidence of synergistic toxicity. Cytochrome P450 loss was significant as early as 3 hr following exposure to BrCCI3, alone or when added with CHCI3. This loss may be attributed to BrCCI3-induced suicide inactivation of cytochrome P450. Centrilobular hepatocytes may be more susceptible to the interactive toxicity of CHCI3 and BrCCI3. Activity of enzymes found predominantly in this area was significantly decreased in slices exposed to both toxicants relative to controls. Conversely, activity of enzymes found predominantly in the periportal region was similar to that of untreated and treated controls. Interactive toxicity of BrCCI3 and CHCI3 was not a consequence of increased lipid peroxidation or depletion of slice glutathione content. Further studies need to be conducted to elucidate the mechanisms mediating the interactive toxicity of BrCCI3 and CHCI3.

UR - http://www.scopus.com/inward/record.url?scp=0028182771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028182771&partnerID=8YFLogxK

U2 - 10.1006/faat.1994.1021

DO - 10.1006/faat.1994.1021

M3 - Article

C2 - 8005369

AN - SCOPUS:0028182771

VL - 22

SP - 172

EP - 177

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -