Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers

Harrison Ozoani; Anthonet N Ezejiofor; Kenneth O Okolo; Chinna N Orish; Ana Cirovic; Aleksandar Cirovic; Orish E Orisakwe

doi:10.1007/s43188-023-00187-z

Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers

Toxicol Res. 2023 May 18;39(3):497-515. doi: 10.1007/s43188-023-00187-z. eCollection 2023 Jul.

Authors

Harrison Ozoani^{1

2}, Anthonet N Ezejiofor¹, Kenneth O Okolo², Chinna N Orish³, Ana Cirovic⁴, Aleksandar Cirovic⁴, Orish E Orisakwe^{1

5}

Affiliations

¹ African Centre of Excellence for Public Health and Toxicological Research (ACE-PUTOR), University of Port Harcourt, PMB, 5323, Port Harcourt, Choba Nigeria.
² Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Science and Technology, Nsukka, Enugu State Nigeria.
³ Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, PMB, 5323, Port Harcourt, Choba Nigeria.
⁴ Faculty of Medicine, Institute of Anatomy, University of Belgrade, Belgrade, Serbia.
⁵ Provictoire Research Institute, Port Harcourt, Rivers State Nigeria.

PMID: 37398573
PMCID: PMC10313602 (available on 2024-07-01)
DOI: 10.1007/s43188-023-00187-z

Abstract

Heavy metals (HMs) such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) are highly toxic elements. They are often found together in nature as a heavy metal mixture (HMM) and are known to contribute to subfertility/infertility as environmental pollutants. This study aims to evaluate the potential benefits of treating HMM-induced testicular pathophysiology with zinc (Zn) and/or selenium (Se). Six-week-old male Sprague Dawley rats were grouped into 5 (n = 7). The control group received deionized water, while the other groups were treated with PbCl₂ (20 mg kg^-1), CdCl₂ (1.61 mg kg^-1), HgCl₂ (0.40 mg kg^-1), and Na₂AsO₃ (10 mg kg^-1) in deionized water for 60 days. Additionally, groups III to V received Zn, Se, and Zn/Se, respectively, for 60 days. The study evaluated testis weight, metal accumulation, sperm analysis, FSH, LH, testosterone, prolactin, oxidative stress, antioxidants, pro-inflammatory and apoptotic markers, and presented structural changes in the testis as micrographs. HMM caused a significant increase in testis weight, metal accumulation, prolactin, oxidative stress, and pro-inflammatory and apoptotic markers, while significantly decreasing semen analysis, FSH, LH, and testosterone. Histology showed decreased spermatogenesis and spermiogenesis, as evidenced by the structure of the germ cells and spermatids. However, Zn, Se, or both ameliorated and reversed some of the observed damages. This study provides further evidence for the mitigative potential of Zn, Se, or both in reversing the damage inflicted by HMM in the testis, and as a countermeasure towards improving HM-induced decrease in public health fecundity.

Keywords: Arsenic; Essential elements; Heavy metals; ROS; Testis.

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