Display options
Cite
Mohammadnejad L, Soltaninejad K, Seyedabadi M, et al. Evaluation of mitochondrial dysfunction due to oxidative stress in therapeutic, toxic and lethal concentrations of tramadol. Toxicol Res (Camb). 2021;10(6):1162-1170doi: 10.1093/toxres/tfab096.
Mohammadnejad, L., Soltaninejad, K., Seyedabadi, M., Ghasem Pouri, S. K., Shokrzadeh, M., & Mohammadi, H. (2021). Evaluation of mitochondrial dysfunction due to oxidative stress in therapeutic, toxic and lethal concentrations of tramadol. Toxicology research, 10(6), 1162-1170. https://doi.org/10.1093/toxres/tfab096
Mohammadnejad, Leila, et al. "Evaluation of mitochondrial dysfunction due to oxidative stress in therapeutic, toxic and lethal concentrations of tramadol." Toxicology research vol. 10,6 (2021): 1162-1170. doi: https://doi.org/10.1093/toxres/tfab096
Mohammadnejad L, Soltaninejad K, Seyedabadi M, Ghasem Pouri SK, Shokrzadeh M, Mohammadi H. Evaluation of mitochondrial dysfunction due to oxidative stress in therapeutic, toxic and lethal concentrations of tramadol. Toxicol Res (Camb). 2021 Nov 08;10(6):1162-1170. doi: 10.1093/toxres/tfab096. eCollection 2021 Dec. PMID: 34956619; PMCID: PMC8692737.
Copy Download .nbib Format: NLM
Share it on

Toxicol Res (Camb). 2021 Nov 08;10(6):1162-1170. doi: 10.1093/toxres/tfab096. eCollection 2021 Dec.

Evaluation of mitochondrial dysfunction due to oxidative stress in therapeutic, toxic and lethal concentrations of tramadol.

Toxicology research

Leila Mohammadnejad, Kambiz Soltaninejad, Mohammad Seyedabadi, Seyed Khosro Ghasem Pouri, Mohammad Shokrzadeh, Hamidreza Mohammadi

Affiliations

  1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran.
  2. Department of Forensic Toxicology, Legal Medicine Research Center, Legal Medicine Organization, Tehran 48157-33971, Iran.
  3. Department of Emergency Medicine, School of Medicine, Antimicrobial Resistance Research Center, Ghaem Shahr Razi Hospital, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran.

PMID: 34956619 PMCID: PMC8692737 DOI: 10.1093/toxres/tfab096

Abstract

Tramadol (TR) is a centrally acting analgesic drug that is used to relieve pain. The therapeutic (0.1-0.8 mg/l), toxic (1-2 mg/l) and lethal (>2 mg/l) ranges were reported for TR. The present study was designed to evaluate which doses of TR can induce liver mitochondrial toxicity. Mitochondria were isolated from the five rats' liver and were incubated with therapeutic to lethal concentrations (1.7-600 μM) of TR. Biomarkers of oxidative stress including: reactive oxygen species (ROS), lipid peroxidation (LPO), protein carbonyl content, glutathione (GSH) content, mitochondrial function, mitochondrial membrane potential (MMP) and mitochondrial swelling were assessed. Our results showed that ROS and LPO at 100 μM and protein carbonylation at 600 μM concentrations of TR were significantly increased. GSH was decreased specifically at 600 μM concentration. Mitochondrial function, MMP and mitochondrial swelling decreased in isolated rat liver mitochondria after exposure to 100 and 300 μM, respectively. This study suggested that TR at therapeutic and toxic levels by single exposure could not induce mitochondrial toxicity. But, in lethal concentration (≥100 μM), TR induced oxidative damage and mitochondria dysfunction. This study suggested that ROS overproduction by increasing of TR concentration induced mitochondrial dysfunction and caused mitochondrial damage via Complex II and membrane permeability transition pores disorders, MMP collapse and mitochondria swelling.

© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Keywords: biomarkers; liver toxicity; mitochondria; oxidative stress; tramadol

Publication Types