Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats

Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

doi:10.1016/j.tox.2017.05.003

Cited by 36 publications

(56 citation statements)

References 52 publications

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“…The main factor responsible for this could be link to off-label use of tramadol as ondemand treatment for premature ejaculation (PE) [15,16]. However, wide-spread use of tramadol is associated with toxicity and a recent study showed that tramadol cause brain, heart and lung toxicity [17]. Therefore, there is need to conduct a study that would examine the toxicity of tramadol in the liver where tramadol is metabolized and, in the kidney, where tramadol metabolites are excreted, thus making liver and kidney the primary toxicity targets for tramadol.…”

Section: Introductionmentioning

confidence: 99%

Hematological and Biochemical Changes in Blood, Liver and Kidney Tissues under the Effect of Tramadol Treatment

Owoade¹,

Adetutu²,

Olorunnisola³

2019

J Alcohol Drug Depend

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This study aimed to investigate the effects of tramadol administration on some haematological and biochemical indices in rats. Tramadol was administered orally to rats for 28 days at a dose of 10 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day. Twenty-four hours after the last tramadol, blood, liver and kidney were removed from the animals after an overnight fast and analysed for their haematological and biochemical parameters. Results obtained revealed that tramadol administration significantly reduced the levels of white blood cells (WBC), red blood cell (RBC), haemoglobin and platelet count (PLT) while its resulted in non-significant changes in other haematological parameters examined when compared with control rats. Tramadol intake significantly increased plasma levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine and urea while its reduced total protein levels. Hepatic and renal thiobarbituric acid reactive substances (TBARS) levels were significantly increased by tramadol administration while levels of endogenous antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were reduced. This study confirmed the risk of increased oxidative stress, hepatotoxicity and nephrotoxicity due to tramadol administration. Although tramadol is reported to be effective in pain management, its toxicity should be kept in mind.

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Section: Introductionmentioning

confidence: 99%

Hematological and Biochemical Changes in Blood, Liver and Kidney Tissues under the Effect of Tramadol Treatment

Owoade¹,

Adetutu²,

Olorunnisola³

2019

J Alcohol Drug Depend

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“…Tramadol is one of the opioid drugs that is extensively used as a pain-killer for chronic pain and cancers [10]. However, multiple tissue toxicities were reported for patients consuming tramadol medication several times a day [13][14][15][16][17]. Since tramadol like other opioids induces oxidative stress which alters cell structure causing apoptosis [21][22][23][24][25], the pomegranate was used in the current study as a protective agent based on its antioxidant activity [34,35,48,49].…”

Section: Discussionmentioning

confidence: 99%

“…Tramadol is used to reduce pain resulted from posttraumatic, obstetric, osteoarthritis, fibromyalgia, renal, biliary colic, and neuropathic pain [12]. However, multiple tissue toxicities were reported when tramadol was administrated [13][14][15][16][17], especially for patients consuming tramadol medication several times daily to relieve chronic pain. We and others have shown that tramadol induces testicular toxicity in adults [5,9,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats

Minisy

Shawki

Omri

et al. 2020

BioMed Research International

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Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.

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“…Such findings come in agreement with those reported by Awadalla & Salah-Eldin (2016) who revealed that tramadol, like other opioids induced intensive histopathological changes in lung tissue of rats and induced decreased antioxidant plasma levels indicating failure of antioxidant defense mechanism against oxidative damage. According to Faria et al (2017), both of tapentadol and tramadol )CNS depressants ( were found to cause severe cellular damage, inflammatory cellular infiltrations and cell death in the pulmonary tissues although tapentadol induced more damage than tramadol.…”

Section: Discussionmentioning

confidence: 99%

Maternal and Fetal Toxicity of Carisoprodol Drug (Somadril Compound) on Pulmonary Tissues of Albino Rats

Emam

2019

JBLS

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Carisoprodol is a common muscle relaxant indicated as adjunctive therapy in acute, painful musculoskeletal cases. This current study aimed to investigate the histopathological, histochemical and immunohistochemical effects in the lung tissue of the pregnant rats and their fetuses after carisoprodol treatment. The present study was applied on twenty seven pregnant female rats and they were randomly divided into three groups (nine pregnant female rats in each group). Rats of the first (control) group were administered oral doses of distilled water. Rats of the second (S1) and third groups (S2) were administered oral doses of carisoprodol in the distilled water equivalent to 10.8 mg and 21.6 mg/100g body weight/day respectively for fifteen days from the six to the twenty day of gestation. Several histopathological, histochemical and some immunohistochemical changes were studied to detect the pathological changes. Maternal and fetal pulmonary tissues of both treated groups showed numerous degenerative changes post-treatment with carisoprodol, the severity of these changes was more obvious in the fetal lung tissue of both groups. Also, carisoprodol treated rats showed a marked increase in caspase-3 content in the maternal and fetal pulmonary tissues. Treatment of pregnant rats with carisoprodol drug led to numerous dystrophic changes in both maternal and fetal lung tissues.

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Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats

Cited by 36 publications

References 52 publications

Hematological and Biochemical Changes in Blood, Liver and Kidney Tissues under the Effect of Tramadol Treatment

Hematological and Biochemical Changes in Blood, Liver and Kidney Tissues under the Effect of Tramadol Treatment

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats

Maternal and Fetal Toxicity of Carisoprodol Drug (Somadril Compound) on Pulmonary Tissues of Albino Rats

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