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Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat

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Abstract

Oxidative stress has been linked with lead toxicity, including lead-induced sexual dysfunction. On the contrary, sodium acetate has been proven to exert antioxidant activity. However, the effect of sodium acetate on lead-induced sexual dysfunction has not been fully explored. This study investigated the effect of sodium acetate on lead-induced sexual dysfunction, exploring the involvement of testosterone, eNOS/NO/cGMP, and Nrf2/HO-1 signaling. Twenty male Wistar rats with similar weights were randomly assigned into four groups (n = 5 rats/group) after two weeks of acclimatization. Animals were vehicle-treated (0.5 ml/day of distilled water, per os), acetate-treated (200 mg/kg/day, per os), lead-treated (20 mg/kg/day, per os), or lead + acetate-treated. The results revealed that sodium acetate treatment attenuated lead-induced rise in penile lead, malondialdehyde and oxidized glutathione concentrations, and acetylcholinesterase activity. In addition, lead exposure prolonged mount, intromission, and ejaculation latency and reduced mount, intromission, and ejaculation frequency, as well as the motivation to mate and penile reflex, which were improved by acetate treatment. More so, acetate treatment ameliorated lead-induced reductions in absolute and relative penile weight, eNOS, NO, cGMP, luteinizing hormone, follicle-stimulating hormone, testosterone, dopamine, Nrf2, HO-1, and reduced glutathione concentrations, as well as glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase activities. In conclusion, this study demonstrates that sodium acetate attenuated lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP and Nrf2/HO-1 signaling. Despite the compelling data presented in this study, other possible associated mechanisms in the protective role of acetate should be explored.

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Data availability

The data used to support the findings of the present study are available from the corresponding author upon request.

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Funding

This study was self-funded.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Basic Medical Sciences, Ebonyi State University, Abakaliki, Nigeria

    E. E. Besong & J. N. Obimma

  2. Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria

    P. J. Ashonibare & R. E. Akhigbe

  3. Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria

    P. J. Ashonibare, T. M. Akhigbe & R. E. Akhigbe

  4. Breeding and Plant Genetics Unit, Department of Agronomy, Osun State University, Osogbo, Osun State, Nigeria

    T. M. Akhigbe

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  1. E. E. Besong
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  2. P. J. Ashonibare
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  3. T. M. Akhigbe
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  4. J. N. Obimma
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  5. R. E. Akhigbe
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Contributions

Conceptualization and design: BEE and ARE. Data analysis: APJ, ATM, and ARE. Funding acquisition: BEE, APJ, ATM, OJN, and ARE. Investigation: BEE, APJ, ATM, OJN, and ARE. Methodology: BEE, APJ, ATM, OJN, and ARE. Project administration: BEE, APJ, ATM, OJN, and ARE. Supervision: BEE, APJ, ATM, OJN, and ARE. Validation: BEE, APJ, ATM, OJN, and ARE. Writing—original draft: APJ and ARE. Writing—review and editing and final approval: BEE, APJ, ATM, OJN, and ARE. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to R. E. Akhigbe.

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Besong, E.E., Ashonibare, P.J., Akhigbe, T.M. et al. Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1233–1243 (2024). https://doi.org/10.1007/s00210-023-02696-y

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