Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat

Anna F. Castoldi, Teresa Coccini, Giovanna Randine, Mariluz Hernández-Viadel, Vicente Felipo, Luigi Manzo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and delayed effects of repeated and acute in vivo CO inhalation were investigated on COX activity, cGMP formation and MR binding in rat brain and lymphocytes to assess whether each endpoint was similarly affected both centrally and peripherally. Male Wistar rats either inhaled 500 ppm CO, 6 h/day, 5 days/week, 4 weeks (repeated exposure) or 2400 ppm, 1 h (single exposure). Neither treatment altered brain or lymphocyte COX activity 1 and 7 days post-treatment. Also ineffective were repeated and acute CO treatments towards 3H-quinuclidinyl benzilate (QNB) binding to MRs in cerebral cortex, hippocampus, striatum, cerebellum (respective controls, mean ± S.D.: 171 ± 45, 245 ± 53, 263 ± 14 and 77 ± 7 fmol/mg protein) and lymphocytes (24 ± 10 fmol/million cells) at the same time points. In lymphocytes control cGMP levels averaged 1.98 ± 0.99 pmol/mg protein under basal conditions, and 3.94 ± 0.55 pmol/mg protein after NO-stimulation. One day after chronic treatment cessation, the CO-treated group displayed about a 50% decrease in both basal and NO-stimulated cGMP values, which persisted up to 7 days after, compared to air-exposed rats. Acutely, CO caused a delayed enhancement (+ 140%) of NO-induced activation of soluble guanylate cyclase. The finding that the NO-cGMP pathway is a target for the delayed effects of CO in peripheral blood cells is in accordance with our data in brain [Hernández-Viadel, M., Castoldi, A.F., Coccini, T., Manzo, L., Erceg, S., Felipo, V., 2004. In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum. Journal of Neurochemistry 89, 1157-1165], and supports the use of this peripheral endpoint as a biomarker of CO central effects.

Original languageEnglish
Pages (from-to)1915-1924
Number of pages10
JournalLife Sciences
Volume78
Issue number17
DOIs
Publication statusPublished - Mar 20 2006

Fingerprint

Lymphocytes
Cyclic GMP
Cholinergic Receptors
Muscarinic Receptors
Electron Transport Complex IV
Carbon Monoxide
Cholinergic Agents
Rats
Nitric Oxide
Brain
Guanylate Cyclase
Cerebellum
Chemical activation
Quinuclidinyl Benzilate
Neurochemistry
Proteins
Withholding Treatment
Biomarkers
Cerebral Cortex
Inhalation

Keywords

  • Central nervous system
  • CO
  • Delayed neurotoxicity
  • Nitric oxide-cGMP pathway
  • Peripheral biomarkers

ASJC Scopus subject areas

  • Pharmacology

Cite this

Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat. / Castoldi, Anna F.; Coccini, Teresa; Randine, Giovanna; Hernández-Viadel, Mariluz; Felipo, Vicente; Manzo, Luigi.

In: Life Sciences, Vol. 78, No. 17, 20.03.2006, p. 1915-1924.

Research output: Contribution to journalArticle

Castoldi, Anna F. ; Coccini, Teresa ; Randine, Giovanna ; Hernández-Viadel, Mariluz ; Felipo, Vicente ; Manzo, Luigi. / Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat. In: Life Sciences. 2006 ; Vol. 78, No. 17. pp. 1915-1924.
@article{83f7aed7615045279be8e3b1c1d59c56,
title = "Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat",
abstract = "Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and delayed effects of repeated and acute in vivo CO inhalation were investigated on COX activity, cGMP formation and MR binding in rat brain and lymphocytes to assess whether each endpoint was similarly affected both centrally and peripherally. Male Wistar rats either inhaled 500 ppm CO, 6 h/day, 5 days/week, 4 weeks (repeated exposure) or 2400 ppm, 1 h (single exposure). Neither treatment altered brain or lymphocyte COX activity 1 and 7 days post-treatment. Also ineffective were repeated and acute CO treatments towards 3H-quinuclidinyl benzilate (QNB) binding to MRs in cerebral cortex, hippocampus, striatum, cerebellum (respective controls, mean ± S.D.: 171 ± 45, 245 ± 53, 263 ± 14 and 77 ± 7 fmol/mg protein) and lymphocytes (24 ± 10 fmol/million cells) at the same time points. In lymphocytes control cGMP levels averaged 1.98 ± 0.99 pmol/mg protein under basal conditions, and 3.94 ± 0.55 pmol/mg protein after NO-stimulation. One day after chronic treatment cessation, the CO-treated group displayed about a 50{\%} decrease in both basal and NO-stimulated cGMP values, which persisted up to 7 days after, compared to air-exposed rats. Acutely, CO caused a delayed enhancement (+ 140{\%}) of NO-induced activation of soluble guanylate cyclase. The finding that the NO-cGMP pathway is a target for the delayed effects of CO in peripheral blood cells is in accordance with our data in brain [Hern{\'a}ndez-Viadel, M., Castoldi, A.F., Coccini, T., Manzo, L., Erceg, S., Felipo, V., 2004. In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum. Journal of Neurochemistry 89, 1157-1165], and supports the use of this peripheral endpoint as a biomarker of CO central effects.",
keywords = "Central nervous system, CO, Delayed neurotoxicity, Nitric oxide-cGMP pathway, Peripheral biomarkers",
author = "Castoldi, {Anna F.} and Teresa Coccini and Giovanna Randine and Mariluz Hern{\'a}ndez-Viadel and Vicente Felipo and Luigi Manzo",
year = "2006",
month = "3",
day = "20",
doi = "10.1016/j.lfs.2005.08.032",
language = "English",
volume = "78",
pages = "1915--1924",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "17",

}

TY - JOUR

T1 - Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors as peripheral indicators of carbon monoxide neurotoxicity after acute and repeated exposure in the rat

AU - Castoldi, Anna F.

AU - Coccini, Teresa

AU - Randine, Giovanna

AU - Hernández-Viadel, Mariluz

AU - Felipo, Vicente

AU - Manzo, Luigi

PY - 2006/3/20

Y1 - 2006/3/20

N2 - Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and delayed effects of repeated and acute in vivo CO inhalation were investigated on COX activity, cGMP formation and MR binding in rat brain and lymphocytes to assess whether each endpoint was similarly affected both centrally and peripherally. Male Wistar rats either inhaled 500 ppm CO, 6 h/day, 5 days/week, 4 weeks (repeated exposure) or 2400 ppm, 1 h (single exposure). Neither treatment altered brain or lymphocyte COX activity 1 and 7 days post-treatment. Also ineffective were repeated and acute CO treatments towards 3H-quinuclidinyl benzilate (QNB) binding to MRs in cerebral cortex, hippocampus, striatum, cerebellum (respective controls, mean ± S.D.: 171 ± 45, 245 ± 53, 263 ± 14 and 77 ± 7 fmol/mg protein) and lymphocytes (24 ± 10 fmol/million cells) at the same time points. In lymphocytes control cGMP levels averaged 1.98 ± 0.99 pmol/mg protein under basal conditions, and 3.94 ± 0.55 pmol/mg protein after NO-stimulation. One day after chronic treatment cessation, the CO-treated group displayed about a 50% decrease in both basal and NO-stimulated cGMP values, which persisted up to 7 days after, compared to air-exposed rats. Acutely, CO caused a delayed enhancement (+ 140%) of NO-induced activation of soluble guanylate cyclase. The finding that the NO-cGMP pathway is a target for the delayed effects of CO in peripheral blood cells is in accordance with our data in brain [Hernández-Viadel, M., Castoldi, A.F., Coccini, T., Manzo, L., Erceg, S., Felipo, V., 2004. In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum. Journal of Neurochemistry 89, 1157-1165], and supports the use of this peripheral endpoint as a biomarker of CO central effects.

AB - Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and delayed effects of repeated and acute in vivo CO inhalation were investigated on COX activity, cGMP formation and MR binding in rat brain and lymphocytes to assess whether each endpoint was similarly affected both centrally and peripherally. Male Wistar rats either inhaled 500 ppm CO, 6 h/day, 5 days/week, 4 weeks (repeated exposure) or 2400 ppm, 1 h (single exposure). Neither treatment altered brain or lymphocyte COX activity 1 and 7 days post-treatment. Also ineffective were repeated and acute CO treatments towards 3H-quinuclidinyl benzilate (QNB) binding to MRs in cerebral cortex, hippocampus, striatum, cerebellum (respective controls, mean ± S.D.: 171 ± 45, 245 ± 53, 263 ± 14 and 77 ± 7 fmol/mg protein) and lymphocytes (24 ± 10 fmol/million cells) at the same time points. In lymphocytes control cGMP levels averaged 1.98 ± 0.99 pmol/mg protein under basal conditions, and 3.94 ± 0.55 pmol/mg protein after NO-stimulation. One day after chronic treatment cessation, the CO-treated group displayed about a 50% decrease in both basal and NO-stimulated cGMP values, which persisted up to 7 days after, compared to air-exposed rats. Acutely, CO caused a delayed enhancement (+ 140%) of NO-induced activation of soluble guanylate cyclase. The finding that the NO-cGMP pathway is a target for the delayed effects of CO in peripheral blood cells is in accordance with our data in brain [Hernández-Viadel, M., Castoldi, A.F., Coccini, T., Manzo, L., Erceg, S., Felipo, V., 2004. In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum. Journal of Neurochemistry 89, 1157-1165], and supports the use of this peripheral endpoint as a biomarker of CO central effects.

KW - Central nervous system

KW - CO

KW - Delayed neurotoxicity

KW - Nitric oxide-cGMP pathway

KW - Peripheral biomarkers

UR - http://www.scopus.com/inward/record.url?scp=33644632826&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644632826&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2005.08.032

DO - 10.1016/j.lfs.2005.08.032

M3 - Article

VL - 78

SP - 1915

EP - 1924

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 17

ER -