Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian; Shahzamani, Mehran; Takhtfooladi, Mohammad Ashrafzadeh; Allahverdi, Amin; Khansari, Mohammadreza

doi:10.5935/abc.20150059

Cited by 10 publications

(11 citation statements)

References 27 publications

(35 reference statements)

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“…Indeed, LPO was now induced in lung and brain cortex, but there seems to be a protective effect in heart tissue. Consistently with this, 20 mg/kg tramadol prevented a rise in cardiac tissue MDA levels in a rat ischemia-reperfusion model [ 72 ]. The authors of the study suggest that tramadol reduces oxidative stress by scavenging peroxyl radicals and increasing antioxidant capacity [ 72 ].…”

Section: Discussionsupporting

confidence: 59%

“…Consistently with this, 20 mg/kg tramadol prevented a rise in cardiac tissue MDA levels in a rat ischemia-reperfusion model [72]. The authors of the study suggest that tramadol reduces oxidative stress by scavenging peroxyl radicals and increasing antioxidant capacity [72]. In this regard, serum MPO results should also be taken into account.…”

Section: Repeated Administration Of Tramadol and Tapentadol Leads Maimentioning

confidence: 53%

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Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

et al. 2021

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Tramadol and tapentadol, two structurally related synthetic opioid analgesics, are widely prescribed due to the enhanced therapeutic profiles resulting from the synergistic combination between μ-opioid receptor (MOR) activation and monoamine reuptake inhibition. However, the number of adverse reactions has been growing along with their increasing use and misuse. The potential toxicological mechanisms for these drugs are not completely understood, especially for tapentadol, owing to its shorter market history. Therefore, in the present study, we aimed to comparatively assess the putative lung, cardiac, and brain cortex toxicological damage elicited by the repeated exposure to therapeutic doses of both prescription opioids. To this purpose, male Wistar rats were intraperitoneally injected with single daily doses of 10, 25, and 50 mg/kg tramadol or tapentadol, corresponding to a standard analgesic dose, an intermediate dose, and the maximum recommended daily dose, respectively, for 14 consecutive days. Such treatment was found to lead mainly to lipid peroxidation and inflammation in lung and brain cortex tissues, as shown through augmented thiobarbituric acid reactive substances (TBARS), as well as to increased serum inflammation biomarkers, such as C reactive protein (CRP) and tumor necrosis factor-α (TNF-α). Cardiomyocyte integrity was also shown to be affected, since both opioids incremented serum lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) activities, while tapentadol was associated with increased serum creatine kinase muscle brain (CK-MB) isoform activity. In turn, the analysis of metabolic parameters in brain cortex tissue revealed increased lactate concentration upon exposure to both drugs, as well as augmented LDH and creatine kinase (CK) activities following tapentadol treatment. In addition, pneumo- and cardiotoxicity biomarkers were quantified at the gene level, while neurotoxicity biomarkers were quantified both at the gene and protein levels; changes in their expression correlate with the oxidative stress, inflammatory, metabolic, and histopathological changes that were detected. Hematoxylin and eosin (H & E) staining revealed several histopathological alterations, including alveolar collapse and destruction in lung sections, inflammatory infiltrates, altered cardiomyocytes and loss of striation in heart sections, degenerated neurons, and accumulation of glial and microglial cells in brain cortex sections. In turn, Masson’s trichrome staining confirmed fibrous tissue deposition in cardiac tissue. Taken as a whole, these results show that the repeated administration of both prescription opioids extends the dose range for which toxicological injury is observed to lower therapeutic doses. They also reinforce previous assumptions that tramadol and tapentadol are not devoid of toxicological risk even at clinical doses.

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Section: Discussionsupporting

confidence: 59%

Section: Repeated Administration Of Tramadol and Tapentadol Leads Maimentioning

confidence: 53%

Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

et al. 2021

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“…Although previous studies showed cardioprotection of tramadol against ischemic-reperfusion insult, [13,52] the current work showed that cardiac and vascular injury was the maximum in the coadministration group manifested by the significant increase in the abso- One of the mechanisms explaining the aggravation of the toxicity in the coadministration group is the alteration of the pharmacokinetics of both drugs by mixing them; Mohammadi et al [53] studied the changes in the pharmacokinetics of tramadol in rats with hepatotoxicity provoked by ethanol through quantifying the concentration of tramadol and its three main metabolites, Odesmethyltramadol (M1), N-desmethyltramadol (M2), and N,O-didesmethyltramadol (M5) using high-performance liquid chromatography; they reported an elevation in the elimination half-life and decreased clearance rate of tramadol together with a decreased area under curve and levels of its three metabolites. On the other hand, Dias et al [54] reported an inhibitory effect of tramadol on the metabolism of alcohol in an in-vitro study using S9 rat liver fractions rich in the main ethanol metabolizing enzyme alcohol dehydrogenase.…”

Section: Discussionmentioning

confidence: 92%

Tramadol aggravates cardiovascular toxicity in a rat model of alcoholism: Involvement of intermediate microfilament proteins and immune‐expressed osteopontin

Hamid

Sabik

Abdelfadeel

et al. 2021

J Biochem & Molecular Tox

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Tramadol and alcohol are among commonly abused drugs. Although there are potential dangers reported upon their mixing, there are no previous reports describing this mixture's effects on the cardiovascular system (CVS). The aim was to study the effects of mixed alcohol and tramadol on the CVS of adult male rats. Fifty rats were divided into four groups: control, tramadol-treated group, alcohol-treated, and coadministration groups. Tramadol caused a significant increases in creatine kinase-MB, troponin I, malondialdehyde, protein carbonyl, 8-hydroxy-2′-deoxyguanosine, and a significant decrease in total antioxidant capacity with histological alterations in sections of the heart and aorta and a significant increase in the area% of collagen fibers while there was a nonsignificant difference in body weight, heart weight, heart weight/body weight ratio, lipid profile, tissue tumor necrosis factor-α and interferon-γ, intermediate microfilament proteins (IFPs) {desmin, vimentin, con-nexin43} gene expression, mean area% of elastic fibers in aortic tissue and osteopontin expression in cardiac and aortic tissue. Alcohol treatment caused a significant change in all the measured parameters and more damage in histological sections.The changes were highest in the coadministration group. There was a strong positive correlation between the area% of collagen fibers and vimentin gene expression, and the area% of osteopontin expression was positively correlated to connexin43 in cardiac and vascular tissue. Tramadol causes CVS injury mainly through oxidative stresses, while the alcohol effect is multifactorial; mixing both aggravates CVS injury. The study also highlights the role of IFPs and osteopontin-expression in inducing injury.

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“…Thus, in the rat model, hypothyroidism, associated with decreased levels of nitric oxide, protected the heart from IR injury. Similarly, physical exercise, 6 administration of tramadol 7 and consumption of nitrate 8 were effective in decreasing IR-induced injury in the rat model. These and other positive results from experimental studies are obfuscated by the fact that to date, cardioprotection strategies in clinical studies have shown negative results.…”

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confidence: 89%

Challenges of Translational Science

García¹,

Polegato²,

Zornoff³

2017

Arquivos Brasileiros De Cardiologia

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Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

Cited by 10 publications

References 27 publications

Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

Tramadol aggravates cardiovascular toxicity in a rat model of alcoholism: Involvement of intermediate microfilament proteins and immune‐expressed osteopontin

Challenges of Translational Science

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