Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment

Awadalla, Eatemad A.; Salah-Eldin, Alaa-Eldin

doi:10.1016/j.biopha.2016.04.024

Cited by 41 publications

(47 citation statements)

References 56 publications

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“…Concomitantly, a previous study on the effect of tramadol on brain/lung tissues demonstrated an increment in pro-apoptotic Bax and Caspase-3 genes expression. 1 By electron microscope, the cerebral and cerebellar cortex of tramadol group showed dramatic ultrastructural changes that confirm our histological findings. Degenerated dense shrunken cells with characters of apoptosis such as corrugated nuclear membrane, chromatin margination and abnormal organelles were observed.…”

supporting

confidence: 77%

“…15 Tramadol group: treated with oral dose of tramadol HCL (40 mg/Kg/day) suspended in saline solution through oro-gastric tube. 1,16 Tramadol + Thyme group treated with combined oral doses of tramadol HCL and thyme extract daily at the same doses and route of administration of Tramadol and Thyme groups.…”

Section: Animals and Experimental Protocolmentioning

confidence: 99%

“…1,2 This dual action promotes an enhanced analgesia with a low incidence of side effects. Disturbance in ER homeostasis will result in ER stress with accumulation of unfolded/misfolded proteins inside its lumen.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

Sarhan

Taalab

2018

Int J Sci Rep

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Background: Tramadol is an opioid analgesic with several adverse reactions. Oxidative and endoplasmic reticulum (ER) stresses have been involved in the molecular mechanisms underlying tramadol neurotoxicity. Importantly, protein kinase RNA-like ER kinase (PERK) is a key ER-downstream pathway that mediates apoptosis. We aimed to determine the cellular stresses interaction that mediates PERK-induced apoptosis in tramadol-treated rats and to assess the effect of thyme in enhancing the antioxidant defense system in the face of such stresses.Methods: Forty male Sprague Dawley rats were randomized into 4 groups. Control group, thyme group received thyme extract (500 mg/kg/day) orally. Tramadol group received tramadol HCL (40 mg/Kg/day) dissolved in saline orally. Tramadol + Thyme group received tramadol and thyme extract. After 30 days, frontal motor and cerebellar cortex specimens were biochemically assessed for oxidative stress biomarkers and evaluated for histological, ultrastructural and immunohistochemical changes. Results: Tramadol group showed a significant elevation in malondialdehyde level with a reduction in superoxide dismutase and catalase enzyme activities. Histologically and ultrastructurally, there were remarkable degenerative and apoptotic changes in the neurons and glial cells. In parallel, we detected a significant increase in integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF compared to control. Tramadol + Thyme group showed improvement in oxidative stress parameters, histological and ultrastructural changes. Moreover, integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF were significantly lower than Tramadol group.Conclusions: Oxidative and ER stress-mediated PERK/apoptosis axis corroborates to the tramadol-induced neurotoxicity. Therapeutic strategies enhancing antioxidant activity and/or blocking ROS-mediated ER stress pathway may resolve tramadol neurotoxicity.

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supporting

confidence: 77%

Section: Animals and Experimental Protocolmentioning

confidence: 99%

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Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

Sarhan

Taalab

2018

Int J Sci Rep

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“…Also, we recorded the molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment [15]. These data confirmed the risk of increased oxidative stress and neuronal and pulmonary damage due to tramadol abuse.…”

Section: Introductionsupporting

confidence: 58%

Chronic Addiction to Tramadol and Withdrawal Effect on the Spermatogenesis and Testicular Tissues in Adult Male Albino Rats

Ibrahim

Salah-Eldin

2019

Pharmacology

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Aim: The present study aimed to elucidate the effects of tramadol on the testicular functions of adult male rats due to the chronic usage of tramadol and the effect of its withdrawal. Method: Adult male albino rats were classified into the following 3 groups: (I) a control administered with normal saline and (II) tramadol-treated rats (40 mg/kg b.w. orally) for 21 successive days; and (III) like the rats in the second group but kept for 4 weeks after the last tramadol dose to study the effect of tramadol withdrawal. At the end of the experimental period, blood was collected and specimens from testis were taken for histopathological, biochemical, and molecular studies. A reverse transcription-polymerized chain reaction after RNA extraction from specimens was detected for the anti-apoptotic and pro-apoptotic genes in testicular tissues. Also, malondialdehyde (MDA) was measured in tissues homogenate and antioxidant enzymes activities were evaluated. Results: The results of this study demonstrated histological changes in testicular tissues in groups II and III compared to the control group, accompanied with increased apoptotic index and proved by increased B-cell lymphoma-2 (Bcl-2) associated-X-protein and caspase-3 expression, whereas anti-apoptotic Bcl-2 markedly decreased. Moreover, in tramadol-abused and -withdrawal groups, the MDA level increased, while the antioxidant enzymes activity decreased and revealed oxidative stress, indicating that tramadol is harmful at the cellular level and can induce apoptotic changes in testicular tissues. The withdrawal effect showed signs of improvement, but it did not return to normal levels. Conclusions: It could be concluded that the administration of tramadol causes abnormalities on testicular tissues associated with oxidative stress, which confirmed the risk of increased oxidative stress on testicular tissues due to tramadol abuse.

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“…Another explanation is that there are evidences about association of tramadol with disorganization of neurons, apoptosis, chromatin changes, blurred nucleolus, intercellular edema, and capillary congestion in brain tissues. Tramadol also increases oxidative stress and cell damages with decreased non-enzymatic anti-oxidative activity, reduced glutathione peroxidase activity, altered glucose metabolism, and suppressed insulin signaling (10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

Complex Partial Seizure and Hippocampus Atrophy Caused by Tramadol Abuse: A Case Study

Ahmadi

Hoseinzade

Haghighi

et al. 2017

Ann Mil Health Sci Res

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Generalized seizure is known as a dose-independent side effect of tramadol. The presented case is affected by complex partial seizures, following tramadol dependency. Brain magnetic imaging showed atrophy of left hippocampus, compatible with mesial temporal sclerosis. Mesial temporal sclerosis is the most common cause of treatment-resistant seizure with etiology of trauma, inflammatory processes, and recurrent seizures. It seems that recurrent generalized seizure by tramadol abuse is responsible for hippocampus atrophy, mesial temporal sclerosis, and complex partial seizures.

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Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment

Cited by 41 publications

References 56 publications

Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

Chronic Addiction to Tramadol and Withdrawal Effect on the Spermatogenesis and Testicular Tissues in Adult Male Albino Rats

Complex Partial Seizure and Hippocampus Atrophy Caused by Tramadol Abuse: A Case Study

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