Erectile dysfunction drugs altered the activities of antioxidant enzymes, oxidative stress and the protein expressions of some cytochrome P450 isozymes involved in the steroidogenesis of steroid hormones

• Published in: PloS one 2020-11, Vol.15 (11), p.e0241509-e0241509
• Main Authors: Sheweita, Salah A, Meftah, Amal A, Sheweita, Mohamed S, Balbaa, Mahmoud E
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - metabolism; Biochemistry; Biology and Life Sciences; Biosynthesis; Catalase; Construction; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochromes P450; Dehydrogenase; Dehydrogenases; Diabetes; DNA damage; Drug dosages; Drugs; Endoplasmic reticulum; Enzyme-linked immunosorbent assay; Enzymes; Erectile dysfunction; Erectile Dysfunction - drug therapy; Erection; Free radicals; Gametocytes; Global health; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Glutathione reductase; Glutathione transferase; Hormones; Hydroxysteroids; Immunoblotting; Infertility; Isoenzymes; Isoenzymes - metabolism; Liver - drug effects; Liver - enzymology; Liver - pathology; Male; Medicine and Health Sciences; Oral administration; Oxidative Stress; Oxygen; Peroxidase; Phosphodiesterase; Phosphodiesterase inhibitors; Protein expression; Proteins; Public health; Rabbits; Reactive oxygen species; Reductases; Research and Analysis Methods; Sildenafil; Sildenafil Citrate - pharmacology; Sildenafil Citrate - therapeutic use; Spectrophotometry; Sperm; Spermatocytes; Steroid hormones; Steroidogenesis; Steroids; Steroids - biosynthesis; Superoxide dismutase; Tadalafil - pharmacology; Tadalafil - therapeutic use; Testes; Testis - drug effects; Testis - pathology; Testosterone; Thiobarbituric Acid Reactive Substances - metabolism; Urology; Vardenafil Dihydrochloride - pharmacology; Vardenafil Dihydrochloride - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0241509

Infertility is a global health problem with about 15 percent of couples involved. About half of the cases of infertility are related to male-related factors. A major cause of infertility in men is oxidative stress, which refers to an imbalance between levels of reactive oxygen species (ROS) and antioxidants. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for the treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by non-antioxidants and antioxidant enzymes. The present study was undertaken to determine if these compounds could have a role in the incidence of infertility, especially after long-term use. Therefore, the present study aims to investigate the effect of EDD on the activities of antioxidant enzymes, free radical levels as well as the protein expression of different cytochrome P450 isozymes involved in the steroidogenesis of different hormones. In addition, the activity of both 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were assayed. The architectures of both livers and testes cells were investigated under the influence of EDD. A daily dose of Sildenafil (1.48 mg/kg), Tadalafil (0.285 mg/kg) and Vardenafil (0.285 mg/kg) were administered orally to male rabbits for 12 week. Western immunoblotting, ELISA, spectrophotometric and histopathological techniques were used in this study. The present study showed that Sildenafil, Vardenafil, and Tadalafil treatments significantly decreased the levels of glutathione and free radicals in both livers and testes of rabbits. Also, Vardenafil and Sildenafil induced the activity of superoxide dismutase and catalase whereas, glutathione S-transferase, glutathione reductase, and glutathione peroxidase activities inhibited in livers of rabbits. The protein expression of cytochrome P450 isozymes (CYP 11A1, 21A2, and 19C) which are involved in the steroidogenesis was markedly changed in both livers and testes of rabbits after their treatments for 12 weeks. After the treatment of rabbits with these medication, the protein expression of CYP11A1 was slightly down-regulated in both livers and testes except Sildenafil up-regulated such protein expression. In addition, the protein expressions of CYP11A1 and CYP 19C in both livers and testes were down-regulated after treatment of rabbits with Sildenafil, Vardenafil, and Tadalafil for 12 wee