Effect of Tadalafil Administration on Redox Homeostasis and Polyamine Levels in Healthy Men with High Level of Physical Activity

Abstract

Background: The phosphodiesterase type 5 inhibitor (PDE5I) tadalafil, in addition to its therapeutic role, has shown antioxidant effects in different in vivo models. Supplementation with antioxidants has received interest as a suitable tool for preventing or reducing exercise-related oxidative stress, possibly leading to the improvement of sport performance in athletes. However, the use/abuse of these substances must be evaluated not only within the context of amateur sport, but especially in competitions where elite athletes are more exposed to stressful physical practice. To date, very few human studies have addressed the influence of the administration of PDE5Is on redox balance in subjects with a fitness level comparable to elite athletes; therefore, the aim of this study was to investigate for the first time whether acute ingestion of tadalafil could affect plasma markers related to cellular damage, redox homeostasis, and blood polyamines levels in healthy subjects with an elevated cardiorespiratory fitness level. Methods: Healthy male volunteers (n = 12), with a VO2max range of 40.1–56.0 mL/(kg × min), were administered with a single dose of tadalafil (20 mg). Plasma molecules related to muscle damage and redox-homeostasis, such as creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), reduced/oxidized glutathione ratio (GSH/GSSG), free thiols (FTH), antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), as well as thiobarbituric acid reactive substances (TBARs), protein carbonyls (PrCAR), and polyamine levels (spermine (Spm) and spermidine (Spd)) were evaluated immediately before and 2, 6 and 24 hours after the acute tadalafil administration. Results: A single tadalafil administration induced an increase in CK and LDH plasma levels 24 after consumption. No effects were observed on redox homeostasis or antioxidant enzyme activities, and neither were they observed on the oxidation target molecules or polyamines levels. Conclusion: Our results show that in subjects with an elevated fitness level, a single administration of tadalafil induced a significant increase in muscle damage target without affecting plasma antioxidant status.

Parental exposure of Tadalafil has beneficial effect on reflexive motor behaviors in mice offspring

“…As oxidation of the fatty acids needs more oxygen than glucose oxidation, elevated oxygen consumption in mitochondrial increases formation of the ROS (Zhang et al, 2021). Glutathione is the primary antioxidant responsible for maintaining a reduced intracellular microenvironment, and Tadalafil administration produced a redox perturbation by the altered GSH/GSSG ratio with no effect on TAS (Duranti, Ceci, et al, 2021; Duranti, Maldini, et al, 2021) which our findings were in agreement to this report. It is assumed that increase in cGMP, directly or indirectly, may lead to modify enzyme activities.…”

“…CAT activity decreased during the development of rodent brain, and administration of the Tadalafil increased CAT levels (Al‐Amin et al, 2014). In this regard, Duranti, Ceci, et al (2021) and Duranti, Maldini, et al (2021) demonstrate that Tadalafil improved oxidative capacity in C2C12 skeletal muscle cells by enhancing fat metabolism. As oxidation of the fatty acids needs more oxygen than glucose oxidation, elevated oxygen consumption in mitochondrial increases formation of the ROS (Zhang et al, 2021).…”

“…Beneficial effects of the Tadalafil on cellular antioxidant system are also reported. Tadalafil increased total intracellular glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) without effect on TAS in C2C12 skeletal muscle (Duranti, Ceci, et al, 2021; Duranti, Maldini, et al, 2021). Single administration of Tadalafil had adverse effect on plasma antioxidant status in men with elevated fitness level (Duranti, Ceci, et al, 2021; Duranti, Maldini, et al, 2021).…”

Hydrogen Peroxide Stimulates Dihydrotestosterone Release in C2C12 Myotubes: A New Perspective for Exercise-Related Muscle Steroidogenesis?

“…Recently, our laboratory, along with others, has demonstrated that PDE5i, including tadalafil, may modulate muscle metabolism and response to ROS under physiological and pathological conditions, in either in vitro or in vivo studies [ 27 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H2O2 Exposure

“…C2C12 myoblasts Trolox ® equivalents antioxidant capacity was evaluated spectrophotometrically, as previously described [ 76 , 77 ]. This assay evaluates the ability of cell lysates in preventing ABTS+ radical formation, compared to Trolox ® (vitamin E analogue) standards.…”