Royal Jelly Abrogates Cadmium-Induced Oxidative Challenge in Mouse Testes: Involvement of the Nrf2 Pathway.

Rafa Almeer,Rami Kassab,Ahmed Abdel Moneim,Gadah Albasher,Saud Alarifi,Dina Metwally,Doaa Soliman,Daoud Ali,Saad Alkahtani

doi:10.3390/ijms19123979

Abstract

The current study examined the efficacy of royal jelly (RJ) against cadmium chloride (CdCl2)-induced testicular dysfunction. A total of 28 Swiss male mice were allocated into four groups (n = 7), and are listed as follows: (1) the control group, who was intraperitoneally injected with physiological saline (0.9% NaCl) for 7 days; (2) the RJ group, who was orally supplemented with RJ (85 mg/kg daily equivalent to 250 mg crude RJ) for 7 days; (3) the CdCl2 group, who was intraperitoneally injected with 6.5 mg/kg for 7 days; and (4) the fourth group, who was supplemented with RJ 1 h before CdCl2 injection for 7 days. Cd-intoxicated mice exhibited a decrease in serum testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. A disturbance in the redox status in the testicular tissue was recorded, as presented by the increase in lipid peroxidation and nitrate/nitrite levels and glutathione (GSH) depletion. Moreover, the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) and their gene expression were inhibited. In addition, interleukin-1ß (IL-1β) and tumor necrosis factor-α (TNF-α) levels were elevated. Furthermore, Cd triggered an apoptotic cascade via upregulation of caspase-3 and Bax and downregulation of Bcl-2. Histopathological examination showed degenerative changes in spermatogenic cells, detachment of the spermatogenic epithelium from the basement membrane, and vacuolated seminiferous tubules. Decreased cell proliferation was reflected by a decrease in proliferating cell nuclear antigen (PCNA) expression. Interestingly, RJ supplementation markedly minimized the biochemical and molecular histopathological changes in testes tissue in response to Cd exposure. The beneficial effects of RJ could be attributed to its antioxidative properties.

Highlights

Cadmium (Cd) is a heavy metal, and is placed between the most ubiquitous environmental toxicants that cause deleterious side effects to the living organisms at low or high levels [1]
Cd has been tightly linked with the overproduction of reactive oxygen species (ROS), which interact with proteins, lipids, carbohydrates, and DNA, and subsequently produce many pathological conditions [2]
Cd concentration was observed to have increased significantly (p < 0.05) in testicular homogenates of mice injected intraperitoneally with CdCl2 for 7 days at a dose of 6.5 mg/kg when compared with the control group

Summary

Introduction

Cadmium (Cd) is a heavy metal, and is placed between the most ubiquitous environmental toxicants that cause deleterious side effects to the living organisms at low or high levels [1]. Cd is associated with the development of several health problems, including reproductive dysfunction, renal failure, cancer, cardiovascular diseases, and neurological disorders [2]. Numerous studies have reported that Cd produces reproductive dysfunctions by disturbing the redox balance, blood-testis barrier, sex hormones homeostasis, sperm count, and enhancing germ cells lose [5,6,7]. Cd is able to enhance a massive cellular inflammatory status through the excessive release of pro-inflammatory mediators, namely interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) (Elmallah et al 2017)

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Conclusion