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The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis

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Abstract

Cadmium (Cd) is widely used in daily life and was recently recognized as a possible source of human toxicity due to its ability to accumulate in organs. Previous studies have shown that Cd exposure may cause testicular toxicity through oxidative stress and an inflammatory effect. Melatonin has been demonstrated to be an effective anti-oxidant and has an anti-inflammatory effect. The aim of the present study was to investigate the toxicological effects of Cd on reproduction in male mice and the potential protective action of melatonin against these adverse effects. Adult male mice were injected intraperitoneally with Cd at a dose of 2 mg/kg body weight per day for seven consecutive days with or without melatonin pretreatment. Sex organ weight, sperm parameters including sperm quality, apoptosis, acrosome integrity, mitochondrial membrane potential, testicular morphology, serum sex hormone, inflammatory status, and oxidative stress were evaluated. The results showed that significant adverse effects were observed in the male reproductive system after Cd exposure, including alterations in sperm parameters, increased DNA damage, and sex hormone disturbance. Acute Cd exposure also significantly increased malondialdehyde (MDA) contents, decreased glutathione (GSH) and superoxide dismutase (SOD) activities, and upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), in the testis. In contrast, melatonin pretreatment significantly alleviated these toxic effects, and its mechanism may involve inhibiting MDA level, restoring GSH and SOD activities, and reducing the upregulation of TNF-α and IL-1β. Our data suggest that oxidative stress and inflammation are involved in Cd-induced toxicity in the male reproductive system and that co-administration of melatonin exerts a protective effect against Cd-induced male reproductive toxicity.

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Abbreviations

Cd:

Cadmium

CdCl2 :

Cadmium chloride

MDA:

Malondialdehyde

TNF-α:

Tumor necrosis factor-alpha

GSH:

Glutathione

SOD:

Superoxide dismutase

ELISA:

Enzyme-linked immunospecific assay

IL-1β:

Interleukin-1beta

AnV:

Annexin-V

MMP:

Mitochondrial membrane potential

PI:

Propidium iodide

PAS:

Periodic acid Schiff

FSH:

Follicle-stimulating hormone

LH:

Luteotropic hormone

SE:

Standard error

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Acknowledgments

We thank all the people who helped us in the present study.

This study was supported by a grant from the Natural Science Foundation of China (Grant No. 81402656), Chongqing Municipal Science and Technology Commission Fundamental Research funded project (Grant Nos. 2014cstc-jbky-01711 and CSTC-2009CA5001), and a grant from the Third Military Medical University (Grant No. 2012XJQ07).

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The authors declare that they have no competing interests.

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Correspondence to Mingfu Ma or Zhiwei Hou.

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Renyan Li and Xue Luo contributed equally to this work.

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Li, R., Luo, X., Li, L. et al. The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis. Biol Trace Elem Res 170, 152–164 (2016). https://doi.org/10.1007/s12011-015-0449-6

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