Hepatotoxicity following separate administration of two phosphodiesterase-5 inhibitors (sildenafil and tadalafil) and opioid (tramadol); evaluation of possible reversal following their withdrawal

Nna, Victor Udo; Akpan, U. P.; Okon, V. E.; Atangwho, Item Justin

doi:10.7324/japs.2015.50817

Cited by 14 publications

(16 citation statements)

References 15 publications

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“…In our previous study, combined administration of sildenafil and tramadol was shown to significantly alter liver functions but these alterations were reversed following withdrawal of treatment with the drugs (Nna et al, 2015b). Our findings also revealed that, combination of sildenafil and tramadol exhibited hypolipidemic effect with poor reversibility following withdrawal of treatment.…”

Section: Introductionsupporting

confidence: 52%

“…Tramadol has been reported to decrease cortisol concentration (Oka et al, 2015), and increase basal metabolic rate and triiodothyronine concentration (Oka et al, 2015). Tramadol has also been reported to significantly alter liver functions (Nna et al, 2015b). In haematological studies conducted by Elyazji et al (2013), tramadol was found to increase WBC count, lymphocyte count and MCV, but decreased PCV, Hb, RBC count, MCH, MCHC and platelets count.…”

Section: Introductionmentioning

confidence: 94%

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High Doses of PDE5 inhibitors and tramadol reversibly alters haematological parameters in rats

Nna¹,

Oka²,

Udefa³

et al. 2016

J App Pharm Sci

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This study examined the effect of chronic administration of PDE5 inhibitors and tramadol on haematological indices because of their reported high incidence of abuse. Additionally, the possibility of reversal of negative effects following withdrawal of treatment was examined. Fifty male rats (180 -200g body weight) were grouped into five (n = 10), namely: control, sildenafil, tadalafil, tramadol and sildenafil+tramadol group. The different groups were orally treated with 0.2mL normal saline, sildenafil (1 mg/100gb.w.), tadalafil (1 mg/100gb.w.), tramadol (2 mg/100g b.w.) and sildenafil + tramadol (1 &2 mg/100gb.w. respectively). Treatment was done thrice a week, for 8 weeks and the animals were allowed access to feed and water ad libitum. Five animals were sacrificed per group, while the remaining 5/group continued for another 8 weeks without drug administration (recovery test).Blood samples were collected from each animal via cardiac puncture at the end of both phases for assessment of haematological parameters. Red blood cells (RBC) count, haemoglobin (Hb) concentration, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution wide standard deviation (RDW-SD), white blood cells (WBCs) count, platelets count, mean platelets volume (MPV) and platelets large cell ratio (P-LCR) were significantly reduced in all the treated groups compared with the control. Following withdrawal of treatment, RBC count, Hb concentration, PCV and red cell absolute values were significantly increased in all recovery groups compared with their respective treated groups. Haematological alterations were reversed following withdrawal of treatment. However, platelet indices were poorly reversed in sildenafil and tramadol recovery groups.

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Section: Introductionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 94%

High Doses of PDE5 inhibitors and tramadol reversibly alters haematological parameters in rats

Nna¹,

Oka²,

Udefa³

et al. 2016

J App Pharm Sci

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“…Sildenafil citrate (Maxheal Laboratories Pvt Ltd, India), tadalafil (Pfizer, India) and tramadol hydrochloride (Glow Pharma Pvt Ltd, India) were purchased from Unipervit Pharmacy, Ikot Omin, Calabar, Nigeria. The different drugs were orally administered, once, every two days as used in our previous reports (Nna, Akpan, Okon, & Atangwho, ; Nna, Akpan, & Osim, ), while the control group received normal saline as vehicle. The drugs were administered to both treatment and recovery groups for 8 weeks, after which animals in the treatment groups (A) were sacrificed under chloroform anaesthesia and the left testis and epididymis carefully harvested for semen analysis, oxidative stress assessment and histopathological examination.…”

Section: Methodsmentioning

confidence: 99%

Testicular toxicity following separate and combined administration of PDE5 inhibitors and opioid: assessment of recovery following their withdrawal

Nna

Osim

2016

Andrologia

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We previously observed that PDE5 inhibitors and opioids were widely abused in Nigeria. Here, we examined the effect of high doses of sildenafil, tadalafil, tramadol and sildenafil + tramadol on reproductive toxicity in male rats. Rats were either administered normal saline (0.2 ml), sildenafil (10 mg/kg), tadalafil (10 mg/kg), tramadol (20 mg/kg) or sildenafil + tramadol (10 and 20 mg/kg respectively) p. o. for 8 weeks. The recovery groups were allowed 8-week recovery period before sacrifice. Results showed that body weight change, testicular and epididymal weights, epididymal sperm count and sperm viability were significantly reduced in all treated groups compared with the control. Spermatozoa with abnormal morphology were significantly increased in all treated groups compared with the control. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) were significantly reduced, while malondialdehyde (MDA) was significantly increased in all treated groups compared with the control. The severity of toxicity was highest in sildenafil + tramadol group. There was no complete recovery from reproductive toxicity following withdrawal of the various treatments. High doses of sildenafil, tadalafil, tramadol or sildenafil + tramadol result in testicular oxidative stress-induced reproductive toxicity with poor reversal following withdrawal.

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“…The phosphodiesterase type 5 inhibitor, sildenafil citrate (SC) and the opioid, tramadol are substances that have been reported to be highly abused in Nigeria [1,2,3]. The reasons behind their abuse are prolongation of erection, postponement of ejaculation and enlargement of genital size [4].…”

Section: Introductionmentioning

confidence: 99%

“…The implication of this is constant bombardment of the liver due to high concentrations of these medications. Both SC and tramadol administered separately and in combination have been reported to damage the liver [2,7,8] by causing oxidative stress [7,9].…”

Section: Introductionmentioning

confidence: 99%

The Hepatotoxic Effect of Sildenafil Citrate and Its Combination with Tramadol on Male Wistar Rats is Ameliorated with Vitamin E Supplementation

Nwangwa

Udefa

M.³

et al. 2019

ACRI

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Aims: This study investigated the effect of vitamin E on serum liver enzymes and bilirubin concentrations in male Wistar rats treated with sildenafil citrate (SC) and a combination of SC and tramadol on the background that these drugs cause oxidative damage to the liver. Methods: Thirty male Wistar rats (180-200 g) were randomly divided into six groups (n=5) thus: control (0.2 ml vehicle – olive oil), SC-treated group (Sil) (10 mg/kg of SC), SC+tramadol-treated group (Sil+Tra) (10 mg/kg of SC and 20 mg/kg of tramadol), vitamin E-treated group (Vit E) (100mg/kg of vitamin E), SC+vitamin E-treated group (Sil+Vit E) (received SC and vitamin E) and SC+tramadol+vitamin E-treated group (Sil+Tra+Vit E) (received SC, tramadol and vitamin E). Drugs were administered orally once daily for four weeks after which blood samples were obtained and used to measure serum concentrations of liver enzymes (AST, ALT and ALP) and bilirubin. Results: Serum AST, ALT, ALP, total bilirubin (TB) and unconjugated bilirubin (UCB) concentrations were significantly (p<0.001) increased in Sil and Sil+Tra compared with control and Vit E and significantly (p<0.01) decreased in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra. Serum conjugated bilirubin (CB) concentration and percentage conjugation of bilirubin significantly decreased (p<0.001) in Sil and Sil+Tra compared with control and Vit E and increased (p<0.01) in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra. Conclusion: SC, administered separately and in combination with tramadol altered liver function. However, vitamin E supplementation was able to ameliorate this alteration in liver function.

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Hepatotoxicity following separate administration of two phosphodiesterase-5 inhibitors (sildenafil and tadalafil) and opioid (tramadol); evaluation of possible reversal following their withdrawal

Cited by 14 publications

References 15 publications

High Doses of PDE5 inhibitors and tramadol reversibly alters haematological parameters in rats

High Doses of PDE5 inhibitors and tramadol reversibly alters haematological parameters in rats

Testicular toxicity following separate and combined administration of PDE5 inhibitors and opioid: assessment of recovery following their withdrawal

The Hepatotoxic Effect of Sildenafil Citrate and Its Combination with Tramadol on Male Wistar Rats is Ameliorated with Vitamin E Supplementation

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