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Alterations in oxidative stress parameters in the testis and epididymis in a nicotine-exposed rat model. Can nicotine-abstinence overcome the oxidative damage?

Login to Access Video or Poster Abstract: MP07-15
Sources of Funding: Grant-In-Aid (KAKENHI) by the Japan Society for the Promotion of Science (25-03102).

Introduction

Epidemiological data indicate that up to 13% of infertility is attributed to cigarette smoking. Nicotine is the most abundant alkaloid chemical in tobacco. We selected nicotine as a major addictive substance of tobacco and investigated its the effects in oxidative stress (OS) changes in epididymis and testis. Additionally we examined if abstinence from nicotine can reverse these changes.

Methods

Eight-week-old Wistar rats were exposed to oral administration of nicotine (15 mg/kg). One group was exposed to nicotine for 10 weeks (Nico-group) and another group was exposed to nicotine for 7 weeks followed by 3 weeks of abstinence (Abst-group). Control animals had access to fresh water. Tissue levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were evaluated both in the testis and the epididymis. Additionally, cotinine levels in the urine, serum and seminal vesicular fluid (SVF) were evaluated. Furthermore, testosterone was measured in the urine samples. Finally, immunohistochemistry was performed for OS-markers and Cytochrome P450 2A6 (CYP2A6) in epididymal tail samples.

Results

Nicotine treatment induced significant increases of MDA levels both in the testis and epididymis in Nico-group compared to Abst and Control groups. TAC was significantly lower in both epididymis and testis in Nico group compared to Abst and Control groups. Cotinine levels in urine, serum and SVF were significantly increased in Nico-group compared to Abst group. Control samples were negative for cotinine. Urine testosterone levels in Nico group were significantly lower compared to Control-group, while there was no significant difference between Control and Abst-group, neither between Nico and Abst groups. Immunohistochemistry revealed mildly stronger intensity for all OS-markers in Nico-group compared with Abst and Control groups. CYP2A6 which is the primary enzyme responsible for the oxidation of nicotine and cotinine was expressed and localized in the epithelial cells of the epididymis in Nico-group.

Conclusions

Our data demonstrate that the harmful effects of nicotine in the testis and epididymis can be reversed by abstinence. Probably treatment with an antioxidant reagent could enhance the antioxidant defenses of testis and epididymis, and further ameliorate the cigarette smoke-induced oxidative stress in both testicular and epididymal tissue. The present data can provide a helpful tool for clinicians to advice smokers, especially those who attend assisted-reproductive programs, to quit smoking.

Funding

Grant-In-Aid (KAKENHI) by the Japan Society for the Promotion of Science (25-03102).

Authors
Panagiota Tsounapi
Masashi Honda
Fotios Dimitriadis
Yusuke Kimura
Shogo Shimizu
Bunya Kawamoto
Katsuya Hikita
Motoaki Saito
Nikolaos Sofikitis
Atsushi Takenaka
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