Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells.
Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death. Cell death was shown to predominantly occur through necrosis, with no alterations in membrane potential or in cytochrome c release. Both drugs were shown to stimulate glucose uptake and to cause ATP depletion, due to changes in the expression of energy metabolism enzymes. The toxicity mechanisms in such a neuronal model are relevant to understand adverse reactions to these opioids and to contribute to dose adjustment in order to avoid neurological damage.
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: julianaffaria@gmail.com.
Juliana
J
Faria
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.
Joana
J
Barbosa
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; CBMA-Center for Molecular Biology and Environment, Department of Biology, University of Minho, Braga, Portugal.
Odília
O
Queirós
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; CBMA-Center for Molecular Biology and Environment, Department of Biology, University of Minho, Braga, Portugal.
Roxana
R
Moreira
UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Félix
F
Carvalho
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: ricardinis@sapo.pt.
Ricardo Jorge
RJ
Dinis-Oliveira
D000255:Adenosine Triphosphate / Q000378:metabolism; D000701:Analgesics, Opioid / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced; D010636:Phenols / Q000633:toxicity*; D000077432:Tapentadol; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014147:Tramadol / Q000633:toxicity*
D000701:Analgesics, Opioid; D010636:Phenols; D017392:Thiobarbituric Acid Reactive Substances; D019344:Lactic Acid; D014147:Tramadol; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D000077432:Tapentadol; D005947:Glucose
Bioenergetics; In vitro; Neurotoxicity; Tapentadol; Tramadol