The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study

Abstract

Purpose

To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency.

Methods

Fifty rats were randomly divided into 5 groups (group-1: sham group-placebo, group-2: bilateral orchiectomy (ORX), group-3: bilateral ORX + tadalafil, group-4: bilateral ORX + testosterone, group-5: bilateral ORX + tadalafil + testosterone). Group-3 received tadalafil (5 mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100 mg/kg i.m., single dose). Group-5 was administered a combination of tadalafil and testosterone undecanoate. All groups were compared with regard to serum nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels.

Results

Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (p = .001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (p = .001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values.

Conclusions

The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.