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Effects of tadalafil administration on plasma markers of exercise-induced muscle damage, IL6 and antioxidant status capacity

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European Journal of Applied Physiology Aims and scope Submit manuscript



Physical exercise is associated with enhanced production of reactive oxygen species, which if uncontrolled can result in tissue injury. Phosphodiesterase type 5 inhibitors (PDE5i) exhibit protective effect against oxidative stress, both in animals and healthy/unhealthy humans. However, the effect of a chronic administration of PDE5i, particularly combined with physical exercise, has never been investigated.


The present study was designed to evaluate the effect of the long-acting PDE5i tadalafil on oxidative status and muscle damage after exhaustive exercise in healthy males included in a double-blind crossover trial.


Tadalafil, having a putative antioxidant activity, may reduce oxidative damage after strenuous exercise.


Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/day) with 36 h of interval before performing exhaustive exercise. After 2 weeks of washout, the volunteers were crossed over. Blood samples were collected immediately before exercise, immediately after, and during recovery (15, 30, 60 min). Plasma total antioxidant status, glutathione homeostasis (GSH/GSSG), malondialdehyde (MDA), protein carbonyls, creatine kinase (CK), lactate dehydrogenase (LDH) and the inflammatory cytokine interleukin 6 were assessed.


Tadalafil administration per se affected redox homeostasis (GSH/GSSG −36 %; p < 0.05), cellular (CK +75 % and LDH +36 %; p < 0.05) and oxidative damage (MDA +41 % and protein carbonyls +50 %; p < 0.05) markers. The exhaustive exercise increased all the above-reported biochemical parameters, with subjects from the tadalafil group showing significantly higher values with respect to the placebo group.


A prolonged exposure to tadalafil decreases antioxidant capacity at resting condition, therefore making subjects more susceptible to the oxidative stress induced by an exhaustive bout of exercise.

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Creatine kinase


Erectile dysfunction


Exhaustive exercise


Interleukin 6


Lactate dehydrogenase




Nitric oxide


Phosphodiesterase type 5 inhibitors


Reduced/oxidized glutathione ratio


Reactive oxygen species


Total antioxidant status

VO2max :

Maximal oxygen uptake


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This work was supported by grants from the University of Rome ‘Foro Italico’ (DIP09-13) to SS. Each author of this study further declares no relationships with the companies or manufacturers who will benefit from the results of the present study.

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The authors of this article declare no conflicts of interest.

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Correspondence to Roberta Ceci.

Additional information

Communicated by Fabio Fischetti.

R. Ceci and G. Duranti contributed equally to this research.

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Ceci, R., Duranti, G., Sgrò, P. et al. Effects of tadalafil administration on plasma markers of exercise-induced muscle damage, IL6 and antioxidant status capacity. Eur J Appl Physiol 115, 531–539 (2015).

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