Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice

Rafael A Cazuza; Gerard Batallé; Xue Bai; Christie R A Leite-Panissi; Olga Pol

doi:10.1016/j.brainresbull.2022.08.004

Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice

Rafael A Cazuza, Gerard Batallé, Xue Bai, Christie R A Leite-Panissi, Olga Pol

Institut de Neurociències (INc)

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9 Cites (Scopus)

Resum

L'activació de l'hemo oxigenasa 1 (HO-1)/monòxid de carboni (CO) inhibeix el dolor crònic inflamatori, però el seu paper en el sistema nerviós central (CNS) no es coneix del tot. Avaluem si el tractament amb un inductor d'HO-1, cobalt protoporfirina IX (CoPP), o una molècula alliberadora de CO, tricarbonildichlororuteni(II) dimer (CORM-2), modula les respostes nociceptives, apoptòtiques i/o oxidatives provocades pel dolor crònic inflamatori en el CNS. En ratolins C57BL/6 mascles amb inflamació perifèrica causada per adjuvant complet de Freund (CFA), avaluem els efectes de CORM-2 i CoPP sobre l'expressió de la proteïna quinasa B (Akt), la proteïna apoptòtica BAX, i les enzims antioxidants HO-1 i NADPH quinona oxidorreductasa 1 (NQO1) en el periaqüeductal gris (PAG), amígdala (AMG), hipocamp ventral (VHPC) i àrea septal medial (MSA). Els nostres resultats van mostrar que l'augment de l'expressió de p-Akt causat per la inflamació perifèrica en les quatre àrees cerebrals analitzades es va revertir amb els tractaments CORM-2 i CoPP. Ambdós tractaments també normalitzaren la regulació a l'alça de BAX induïda per CFA en el PAG i MSA. L'estrès oxidatiu, demostrat amb la disminució d'expressió d'HO-1 al PAG i AMG, es va normalitzar en els animals tractats amb CoPP i CORM-2. La CoPP també va augmentar l'expressió de HO-1 a VHPC, i tots dos tractaments van regularitzar els nivells NQO1 en el PAG dels animals injectats amb CFA. En conclusió, tant els tractaments CORM-2 com CoPP inhibeixen les respostes nociceptives i apoptòtiques generades per la inflamació perifèrica i/o potencien les respostes antioxidants en diverses àrees cerebrals que revelen nous efectes moduladors d'aquests tractaments al CNS dels animals amb dolor crònic inflamatori.

Idioma original	Anglès
Pàgines (de-a)	169-178
Nombre de pàgines	10
Revista	Brain Research Bulletin
Volum	188
DOIs	https://doi.org/10.1016/j.brainresbull.2022.08.004
Estat de la publicació	Publicada - 1 d’oct. 2022

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10.1016/j.brainresbull.2022.08.004Llicència: C In Copyright

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https://www.scopus.com/pages/publications/85135770183

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Cazuza, R. A., Batallé, G., Bai, X., Leite-Panissi, C. R. A., & Pol, O. (2022). Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice. Brain Research Bulletin, 188, 169-178. https://doi.org/10.1016/j.brainresbull.2022.08.004

@article{8093e443ec8d48dda6ccf7c21262fc74,

title = "Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice",

abstract = "The activation of heme oxygenase 1 (HO-1)/carbon monoxide (CO) inhibits chronic inflammatory pain, but its role in the central nervous system (CNS) is not entirely known. We evaluated whether the treatment with an HO-1 inducer, cobalt protoporphyrin IX (CoPP), or a CO-releasing molecule, tricarbonyldichlororuthenium(II)dimer (CORM-2), modulates the nociceptive, apoptotic and/or oxidative responses provoked by persistent inflammatory pain in the CNS. In C57BL/6 male mice with peripheral inflammation caused by complete Freund's adjuvant (CFA), we assessed the effects of CORM-2 and CoPP on the expression of protein kinase B (Akt), the apoptotic protein BAX, and the antioxidant enzymes HO-1 and NADPH quinone oxidoreductase 1 (NQO1) in the periaqueductal gray matter (PAG), amygdala (AMG), ventral hippocampus (VHPC) and medial septal area (MSA). Our results showed that the increased expression of p-Akt caused by peripheral inflammation in the four analyzed brain areas was reversed by CORM-2 and CoPP therapies. Both treatments also normalized the upregulation of BAX induced by CFA on the VHPC and MSA. Oxidative stress, demonstrated with the decreased expression of HO-1 on the PAG and AMG, was normalized in CORM-2 and CoPP treated animals. CoPP also increased the expression of HO-1 on VHPC, and both treatments up-regulated the NQO1 levels on the PAG of CFA-injected animals. In conclusion, both CORM-2 and CoPP treatments inhibited the nociceptive and apoptotic responses generated by peripheral inflammation and/or potentiated the antioxidant responses in several brain areas revealing the new modulatory effects of these treatments in the CNS of animals with chronic inflammatory pain.",

keywords = "Animals, Antioxidants/metabolism, Carbon Monoxide/metabolism, Central Nervous System/metabolism, Chronic Pain/metabolism, Heme Oxygenase-1/metabolism, Inflammation/drug therapy, Male, Mice, Mice, Inbred C57BL, Nociception, Organometallic Compounds/metabolism, Oxidative Stress, Proto-Oncogene Proteins c-akt/metabolism, bcl-2-Associated X Protein/metabolism",

author = "Cazuza, \{Rafael A\} and Gerard Batall{\'e} and Xue Bai and Leite-Panissi, \{Christie R A\} and Olga Pol",

year = "2022",

month = oct,

day = "1",

doi = "10.1016/j.brainresbull.2022.08.004",

language = "English",

volume = "188",

pages = "169--178",

journal = "Brain Research Bulletin",

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publisher = "Elsevier Inc.",

}

Cazuza, RA, Batallé, G, Bai, X, Leite-Panissi, CRA & Pol, O 2022, 'Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice', Brain Research Bulletin, vol. 188, pàg. 169-178. https://doi.org/10.1016/j.brainresbull.2022.08.004

Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice. / Cazuza, Rafael A; Batallé, Gerard; Bai, Xue et al.
In: Brain Research Bulletin, Vol. 188, 01.10.2022, pàg. 169-178.

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

TY - JOUR

T1 - Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice

AU - Cazuza, Rafael A

AU - Batallé, Gerard

AU - Bai, Xue

AU - Leite-Panissi, Christie R A

AU - Pol, Olga

PY - 2022/10/1

Y1 - 2022/10/1

N2 - The activation of heme oxygenase 1 (HO-1)/carbon monoxide (CO) inhibits chronic inflammatory pain, but its role in the central nervous system (CNS) is not entirely known. We evaluated whether the treatment with an HO-1 inducer, cobalt protoporphyrin IX (CoPP), or a CO-releasing molecule, tricarbonyldichlororuthenium(II)dimer (CORM-2), modulates the nociceptive, apoptotic and/or oxidative responses provoked by persistent inflammatory pain in the CNS. In C57BL/6 male mice with peripheral inflammation caused by complete Freund's adjuvant (CFA), we assessed the effects of CORM-2 and CoPP on the expression of protein kinase B (Akt), the apoptotic protein BAX, and the antioxidant enzymes HO-1 and NADPH quinone oxidoreductase 1 (NQO1) in the periaqueductal gray matter (PAG), amygdala (AMG), ventral hippocampus (VHPC) and medial septal area (MSA). Our results showed that the increased expression of p-Akt caused by peripheral inflammation in the four analyzed brain areas was reversed by CORM-2 and CoPP therapies. Both treatments also normalized the upregulation of BAX induced by CFA on the VHPC and MSA. Oxidative stress, demonstrated with the decreased expression of HO-1 on the PAG and AMG, was normalized in CORM-2 and CoPP treated animals. CoPP also increased the expression of HO-1 on VHPC, and both treatments up-regulated the NQO1 levels on the PAG of CFA-injected animals. In conclusion, both CORM-2 and CoPP treatments inhibited the nociceptive and apoptotic responses generated by peripheral inflammation and/or potentiated the antioxidant responses in several brain areas revealing the new modulatory effects of these treatments in the CNS of animals with chronic inflammatory pain.

AB - The activation of heme oxygenase 1 (HO-1)/carbon monoxide (CO) inhibits chronic inflammatory pain, but its role in the central nervous system (CNS) is not entirely known. We evaluated whether the treatment with an HO-1 inducer, cobalt protoporphyrin IX (CoPP), or a CO-releasing molecule, tricarbonyldichlororuthenium(II)dimer (CORM-2), modulates the nociceptive, apoptotic and/or oxidative responses provoked by persistent inflammatory pain in the CNS. In C57BL/6 male mice with peripheral inflammation caused by complete Freund's adjuvant (CFA), we assessed the effects of CORM-2 and CoPP on the expression of protein kinase B (Akt), the apoptotic protein BAX, and the antioxidant enzymes HO-1 and NADPH quinone oxidoreductase 1 (NQO1) in the periaqueductal gray matter (PAG), amygdala (AMG), ventral hippocampus (VHPC) and medial septal area (MSA). Our results showed that the increased expression of p-Akt caused by peripheral inflammation in the four analyzed brain areas was reversed by CORM-2 and CoPP therapies. Both treatments also normalized the upregulation of BAX induced by CFA on the VHPC and MSA. Oxidative stress, demonstrated with the decreased expression of HO-1 on the PAG and AMG, was normalized in CORM-2 and CoPP treated animals. CoPP also increased the expression of HO-1 on VHPC, and both treatments up-regulated the NQO1 levels on the PAG of CFA-injected animals. In conclusion, both CORM-2 and CoPP treatments inhibited the nociceptive and apoptotic responses generated by peripheral inflammation and/or potentiated the antioxidant responses in several brain areas revealing the new modulatory effects of these treatments in the CNS of animals with chronic inflammatory pain.

KW - Animals

KW - Antioxidants/metabolism

KW - Carbon Monoxide/metabolism

KW - Central Nervous System/metabolism

KW - Chronic Pain/metabolism

KW - Heme Oxygenase-1/metabolism

KW - Inflammation/drug therapy

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Nociception

KW - Organometallic Compounds/metabolism

KW - Oxidative Stress

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - bcl-2-Associated X Protein/metabolism

UR - https://www.scopus.com/pages/publications/85135770183

U2 - 10.1016/j.brainresbull.2022.08.004

DO - 10.1016/j.brainresbull.2022.08.004

M3 - Article

C2 - 35952846

SN - 0361-9230

VL - 188

SP - 169

EP - 178

JO - Brain Research Bulletin

JF - Brain Research Bulletin

ER -

Cazuza RA, Batallé G, Bai X, Leite-Panissi CRA, Pol O. Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice. Brain Research Bulletin. 2022 oct. 1;188:169-178. doi: 10.1016/j.brainresbull.2022.08.004