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Atorvastatin modulates drug transporters and ameliorates nicotine‐induced testicular toxicity
Author(s) -
Syam Das S.,
Nair S. S.,
Indira M.
Publication year - 2018
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.13029
Subject(s) - atorvastatin , nicotine , pharmacology , efflux , transporter , chemistry , toxicity , endocrinology , medicine , biochemistry , gene
Summary We studied the changes in m RNA 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 SLCOB 1, SLC 22A1 and efflux transporter ABCB 1 associated with transport of atorvastatin and nicotine, and proteins of BTB were assayed. Nicotine administration activated apoptosis and downregulated SLCOB 1, which transport atorvastatin. Atorvastatin administration suppressed apoptotic pathway and downregulated SLC 22A1, 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.