Prevention and reversal of chlorpromazine induced testicular dysfunction in rats by synergistic testicle-active flavonoids, taurine and coenzyme-10

Reprod Toxicol. 2021 Apr:101:50-62. doi: 10.1016/j.reprotox.2021.01.013. Epub 2021 Feb 3.

Abstract

Evidences have shown that alterations in testicular dehydrogenase and ionic-ATPase activities have important implications in spermatogenesis and sperm capacitation, a penultimate biochemical change required for fertilization. Previous studies have revealed that taurine and coenzyme-Q10 (COQ-10), which are synergistic testicle-active bioflavonoids, with proven gonadotropin-enhancing properties reduce testicular damage in rats. Hence, this study investigated the effects of taurine and COQ-10 or their combination alone, and in the preventive and reversal of chlorpromazine-induced inhibition of testicular dehydrogenase enzymes, electrogenic pumps, sperm capacitation and acrosomal-reaction in male Wister rats. In the drug-treatment alone or preventive-protocol, rats received oral treatment of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or both alone repeatedly for 56 days, or in combination with chlorpromazine (30 mg/kg/p.o./day) from days 29-56. In the reversal-protocol, the animals received chlorpromazine for 56 days prior to saline, taurine, COQ-10 or the combination from days 29-56. Thereafter, spermatogenesis (sperm count, viability, motility and morphology), testicular dehydrogenase [3beta-hydroxysteroid dehydrogenase (3ß-HSD), 17beta-hydroxysteroid dehydrogenase (17ß-HSD), glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase-X (LDH-X)], ATPase (Na+/K+, Ca2+, Mg2+, H+) activities, sperm capacitation and acrosomal reaction were evaluated. Taurine and COQ-10 or their combination increased spermatogenesis, testicular 3ß-HSD, 17ß-HSD, G6PDH and LDH-X enzymes of naïve and chlorpromazine-treated rats. Both taurine and COQ-10 increased Na+/K+, Ca2+, Mg2+ and H+-ATPase activities. Also, taurine and COQ-10 or their combination prevented and reversed chlorpromazine-induced inhibition of sperm capacitation and acrosomal-reaction. The study showed that taurine and COQ-10 prevent and reverse chlorpromazine-induced inhibition of spermatogenesis, epididymal sperm capacitation and acrosomal reaction in rats through increased testicular dehydrogenases and electrogenic pump activities.

Keywords: ATPase activity; Antipsychotics; Coenzyme QIO; Dihydrogenase enzyme; Steriodogenesis; Taurine.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / metabolism
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Antipsychotic Agents / toxicity*
  • Chlorpromazine / toxicity*
  • Coenzymes / pharmacology
  • Coenzymes / therapeutic use*
  • Drug Synergism
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Glucosephosphate Dehydrogenase / metabolism
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Wistar
  • Sperm Count
  • Sperm Motility
  • Spermatozoa / drug effects
  • Spermatozoa / physiology
  • Taurine / pharmacology
  • Taurine / therapeutic use*
  • Testis / drug effects*
  • Testis / metabolism

Substances

  • Antipsychotic Agents
  • Coenzymes
  • Flavonoids
  • Isoenzymes
  • Protective Agents
  • Taurine
  • 17-Hydroxysteroid Dehydrogenases
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase C4
  • Glucosephosphate Dehydrogenase
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Adenosine Triphosphatases
  • Chlorpromazine