Atorvastatin modulates drug transporters and ameliorates nicotine-induced testicular toxicity

S Syam Das1, S S Nair1, M Indira1

  • 1Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.

Andrologia
|May 10, 2018
PubMed

Insights

Atorvastatin ameliorates nicotine-induced testicular toxicity by altering drug transporters and blood-testis-barrier (BTB) proteins. Coadministration reduced apoptosis and improved testicular function in rats.

Area of Science:

  • Reproductive toxicology
  • Pharmacology
  • Biochemistry

Background:

  • Nicotine exposure can induce testicular toxicity and apoptosis.
  • Atorvastatin, a cholesterol-lowering drug, may influence drug transporter expression.
  • The blood-testis barrier (BTB) regulates the passage of substances into the testis.

Purpose of the Study:

  • To investigate the effects of coadministering nicotine and atorvastatin on testicular function in rats.
  • To examine changes in mRNA expression of drug transporters, BTB proteins, and apoptotic genes.
  • To elucidate the protective mechanisms of atorvastatin against nicotine-induced testicular toxicity.

Main Methods:

  • Rats were divided into control, atorvastatin-only, nicotine-only, and combined treatment groups.
  • Treatments involved oral atorvastatin (10 mg/kg) and intraperitoneal nicotine (0.6 mg/kg) for 60 days.
  • mRNA expression of apoptotic genes, influx transporters (SLCOB1, SLC22A1), efflux transporter (ABCB1), and BTB proteins were analyzed.

Main Results:

  • Nicotine alone upregulated apoptosis and downregulated SLCOB1 (atorvastatin transporter).
  • Atorvastatin alone downregulated SLC22A1 (nicotine transporter) and suppressed apoptosis.
  • Combined treatment downregulated apoptotic genes, reduced influx, enhanced efflux of both drugs, and improved testicular function.

Conclusions:

  • Atorvastatin ameliorates nicotine-induced testicular toxicity.
  • Alterations in blood-testis-barrier (BTB) proteins and drug transporters by atorvastatin play a key role.
  • Combined administration modifies drug transport and testicular microenvironment, improving function.

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