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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.
Abstract:
We studied the changes in mRNA expressions of influx and efflux transporters, blood-testis-barrier proteins (BTB) and key apoptotic genes in the testis of rats coadministered with nicotine and atorvastatin. Rats were divided into four groups: (i) control, (ii) atorvastatin (10 mg/kg b.wt), (iii) nicotine (0.6 mg/kg b.wt) and (iv) atorvastatin (10 mg/kg b.wt) + nicotine (0.6 mg/kg b.wt). Atorvastatin was given by oral intubation and nicotine by intraperitoneal injection. After 60 days of treatment, expressions of key apoptotic genes involved in both intrinsic and extrinsic pathways; solute carrier influx transporters SLCOB1, SLC22A1 and efflux transporter ABCB1 associated with transport of atorvastatin and nicotine, and proteins of BTB were assayed. Nicotine administration activated apoptosis and downregulated SLCOB1, which transport atorvastatin. Atorvastatin administration suppressed apoptotic pathway and downregulated SLC22A1, transporter of nicotine. Coadministration of atorvastatin with nicotine downregulated expressions of apoptotic genes. The combined administration of atorvastatin and nicotine reduced the influx of both atorvastatin and nicotine and enhanced the efflux of these drugs thereby altering the microenvironment of testis and improving testicular function. We conclude that atorvastatin-mediated alterations of BTB and drug transporters might have played a significant role in ameliorating nicotine-induced testicular toxicity.
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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