Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats

Ali, Haytham; Afifi, Mohamed; Saber, Taghred M.; Makki, Arwa A.; Keshta, Akaber T.; Baeshen, Mohammed N.; Al‐Farga, Ammar

doi:10.1007/s12031-020-01592-x

Cited by 23 publications

(19 citation statements)

References 44 publications

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“…Tramadol HCL induces neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress (Ali et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Tramadol Biological Effects: 4: Effective Therapeutic Efficacy ofLagenaria sicerariaPreparation (Gamal & Aref1) and Melatonin on Cell Biological, Histochemical, and Histopathological Changes in the Kidney of Tramadol-Induced Male Mice

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Tramadol Biological Effects: 4: Effective Therapeutic Efficacy ofLagenaria sicerariaPreparation (Gamal & Aref1) and Melatonin on Cell Biological, Histochemical, and Histopathological Changes in the Kidney of Tramadol-Induced Male Mice

et al. 2021

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“…Behavioral problems and cognitive function impairment are other side effects of tramadol. Previous results indicate that tramadol is responsible for neurodegeneration in the prefrontal cortex through activation of neuroinflammatory response 33 .…”

Section: Tramadolmentioning

confidence: 99%

An Updated Review on Some Neurotoxic Pharmacological Agents Along with their Neurotoxic Mechanisms

Bashir¹,

Aziz²,

Noor³

2021

IJFMT

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This review will provide the vital information about some pharmacological agents which are Neurotoxic. Through this update, Anti-cancer, Anti-bacterial, Analgesic, Psychoactive drug and Anabolic steroid medication are reported briefly regarding their neurotoxic mechanisms. In this review all information regarding neurotoxic drugs is collected from 2020 published work by Web of science, Scopus, PubMed and Google Scholar. It is concluded that all these drugs which the part of our study are neurotoxic. There is need to discover some method to reduce their toxicity and to avoid the chronic use of these medications.

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“…Although their dose determines their overall effect on the oxidation status, opioids are known to induce oxidative stress, with multiple studies reporting increased serum and tissue oxidative stress biomarkers and decreased antioxidant defense mechanisms. Decreased brain glutathione, glutathione peroxidase, and superoxide dismutase (SOD) activities, as well as increased brain malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), and 8-hidroxydeoxyguanosine levels, have been described in mice and rat models repeatedly administered with 20 to 168 mg/kg tramadol, through different routes [60,62,[67][68][69][70][71]. Furthermore, under the conditions assayed in the present study, we have previously shown increased TBARS-a surrogate of lipid peroxidation (LPO)-and protein carbonyl groups-indicative of protein oxidation-in liver and kidney homogenates from Wistar rats exposed to both tramadol and tapentadol [57].…”

Section: Repeated Administration Of Tramadol and Tapentadol Leads Maimentioning

confidence: 99%

“…These results are also in line with those from similar studies, mostly concerning rat consecutive administration with tramadol doses ranging from 25 to 200 mg/kg, for periods up to 60 days. Such studies report disorganized cortical layers and hypercellularity [59][60][61][62], as well as degenerated, vacuolated neurons, irregular in shape, with pyknotic and vacuolated nuclei, often with heterogeneous pigmentation and evident signs of apoptosis [58][59][60][61][62]70,[164][165][166]. Neuronal degeneration and histological changes have been correlated with glucose metabolism alterations and with the bioenergetic crisis discussed in Section 3.4 [55,60].…”

Section: Repeated Exposure To Tramadol and Tapentadol Leads To Histopmentioning

confidence: 99%

“…Cellular infiltrates are also mentioned in these studies [58,60,164], as well as gliosis, satellitosis, and microglial and oligodendrocyte proliferation [58,62,144,164]. Vascular dilatation and congestion, hemorrhage, and brain edema are also cited [58][59][60][61][62]70,164,166]. Indeed, severe brain edema and hypoxic brain damage are reported in opiate-related deaths, including those from tramadol [39,40,45,161].…”

Section: Repeated Exposure To Tramadol and Tapentadol Leads To Histopmentioning

confidence: 99%

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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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Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats

Cited by 23 publications

References 44 publications

Tramadol Biological Effects: 4: Effective Therapeutic Efficacy ofLagenaria sicerariaPreparation (Gamal & Aref1) and Melatonin on Cell Biological, Histochemical, and Histopathological Changes in the Kidney of Tramadol-Induced Male Mice

Tramadol Biological Effects: 4: Effective Therapeutic Efficacy ofLagenaria sicerariaPreparation (Gamal & Aref1) and Melatonin on Cell Biological, Histochemical, and Histopathological Changes in the Kidney of Tramadol-Induced Male Mice

An Updated Review on Some Neurotoxic Pharmacological Agents Along with their Neurotoxic Mechanisms

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

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