Your browser doesn't support javascript.
loading
Neuroprotective potential of trimetazidine against tramadol-induced neurotoxicity: role of PI3K/Akt/mTOR signaling pathways.
Kamranian, Houman; Asoudeh, Hadi; Sharif, Roya Kamrani; Taheri, Fereshteh; Hayes, A Wallace; Gholami, Mina; Alavi, Ahmad; Motaghinejad, Majid.
Afiliação
  • Kamranian H; Department of Psychiatry, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
  • Asoudeh H; Faculty of Pharmacy, Central Branch of Islamic Azad University, Tehran, Iran.
  • Sharif RK; Faculty of Veterinary, University of Tehran, Tehran, Iran.
  • Taheri F; Department of Medicine, Islamic Azad University, Qom Branch, Iran.
  • Hayes AW; University of South Florida College of Public Health, Tampa, FL, USA and Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
  • Gholami M; Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Alavi A; Department of Medicine, Islamic Azad University, Qom Branch, Iran.
  • Motaghinejad M; Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Toxicol Mech Methods ; 33(7): 607-623, 2023 Sep.
Article em En | MEDLINE | ID: mdl-37051630
ABSTRACT
Tramadol (TRA) causes neurotoxicity whereas trimetazidine (TMZ) is neuroprotective. The potential involvement of the PI3K/Akt/mTOR signaling pathway in the neuroprotection of TMZ against TRA-induced neurotoxicity was evaluated. Seventy male Wistar rats were divided into groups. Groups 1 and 2 received saline or TRA (50 mg/kg). Groups 3, 4, and 5 received TRA (50 mg/kg) and TMZ (40, 80, or 160 mg/kg) for 14 days. Group 6 received TMZ (160 mg/kg). Hippocampal neurodegenerative, mitochondrial quadruple complex enzymes, phosphatidylinositol-3-kinases (PI3Ks)/protein kinase B levels, oxidative stress, inflammatory, apoptosis, autophagy, and histopathology were evaluated. TMZ decreased anxiety and depressive-like behavior induced by TRA. TMZ in tramadol-treated animals inhibited lipid peroxidation, GSSG, TNF-α, and IL-1ß while increasing GSH, SOD, GPx, GR, and mitochondrial quadruple complex enzymes in the hippocampus. TRA inhibited Glial fibrillary acidic protein expression and increased pyruvate dehydrogenase levels. TMZ reduced these changes. TRA decreased the level of JNK and increased Beclin-1 and Bax. TMZ decreased phosphorylated Bcl-2 while increasing the unphosphorylated form in tramadol-treated rats. TMZ activated phosphorylated PI3Ks, Akt, and mTOR proteins. TMZ inhibited tramadol-induced neurotoxicity by modulating the PI3K/Akt/mTOR signaling pathways and its downstream inflammatory, apoptosis, and autophagy-related cascades.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tramadol / Trimetazidina / Fármacos Neuroprotetores / Síndromes Neurotóxicas Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tramadol / Trimetazidina / Fármacos Neuroprotetores / Síndromes Neurotóxicas Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article