title: Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.
abstract: The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively.
authors.affiliation: Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt tarek967@hotmail.com.
authors.forename: Tarek Mostafa
authors.initials: TM
authors.lastname: Mohamed
authors.affiliation: Forensic Medicine and Clinical toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Hamdy M Abdel
authors.initials: HM
authors.lastname: Ghaffar
authors.affiliation: Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
authors.forename: Rabee M R
authors.initials: RM
authors.lastname: El Husseiny
mesh_terms: D000701:Analgesics, Opioid / Q000506:poisoning; D000818:Animals; D000927:Anticonvulsants / Q000506:poisoning; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002998:Clonazepam / Q000506:poisoning; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D042963:Electron Transport Complex II / Q000187:drug effects / Q000378:metabolism; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D009293:Opioid-Related Disorders / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D036301:Qualitative Research; D011897:Random Allocation; D051381:Rats; D019966:Substance-Related Disorders / Q000150:complications / Q000201:enzymology / Q000473:pathology; D014147:Tramadol / Q000506:poisoning*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D000927:Anticonvulsants; D009419:Nerve Tissue Proteins; D014147:Tramadol; D002998:Clonazepam; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
keywords: Tramadol; abuse; clonazepam; mitochondrial electron transport