Protective effect of naringenin against cadmium-induced testicular toxicity in male SD rats

Wang, Jicang; Zhu, Huali; Lin, Shu Qian; Wang, Ke; Wang, Hongwei; Liu, Zongping

doi:10.1016/j.jinorgbio.2020.111310

Cited by 35 publications

(14 citation statements)

References 43 publications

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“…Intra-peritoneal injection of rats with Cd for 21 days resulted in severe histological damage in the testicular tissue together with an alteration of sperm cell activity [ 14 ]. Moreover, Cd was reported to accumulate in serum and testes when administered for 4 weeks; this induced depletion of testicular enzymatic antioxidants, impairment of serum gonadotrophin hormones and the enhancing of testicular autophagy [ 15 ]. Furthermore, Cd decreased libido, fertility and testosterone levels [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Physiological Roles of Red Carrot Methanolic Extract and Vitamin E to Abrogate Cadmium-Induced Oxidative Challenge and Apoptosis in Rat Testes: Involvement of the Bax/Bcl-2 Ratio

et al. 2021

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The precise analysis of the contents of the red carrot is still ambiguous and its role in the maintenance of male fertility needs to be further reconnoitered. Hence, this study targets the physiological impacts of either red carrot methanolic extract (RCME) or vitamin E (Vit. E), co-administrated with cadmium chloride (CdCl2) on rat testes, specifically those concerned with apoptosis and oxidative challenge. Four groups of adult male rats (n = 12) are used; control, CdCl2, CdCl2+Vit. E and CdCl2 + RCME. LC-MS analysis of RCME reveals the presence of 20 different phytochemical compounds. Our data clarify the deleterious effects of CdCl2 on testicular weights, semen quality, serum hormonal profile, oxidative markers and Bax/ Bcl-2 ratio. Histopathological changes in testicular, prostatic and semen vesicle glandular tissues are also observed. Interestingly, our data clearly demonstrate that co-administration of either RCME or Vit. E with CdCl2 significantly succeeded in the modulation (p < 0.05) of all of these negative effects. The most striking is that they were potent enough to modulate the Bax/Bcl-2 ratio as well as having the ability to correct the impaired semen picture, oxidant status and hormonal profile. Thus, RCME and Vit. E could be used as effective prophylactic treatments to protect the male reproductive physiology against CdCl2 insult.

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Section: Introductionmentioning

confidence: 99%

Physiological Roles of Red Carrot Methanolic Extract and Vitamin E to Abrogate Cadmium-Induced Oxidative Challenge and Apoptosis in Rat Testes: Involvement of the Bax/Bcl-2 Ratio

et al. 2021

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“…There is a general consensus about the involvement of Cd‐mediated oxidative and anti‐oxidative stress in testicular pathogenesis (Elmallah et al ., 2017; Yang et al ., 2019). However, Cd has been shown to induce the oxidative damage by inhibiting the body's antioxidant system, leading to production of reactive oxygen species (ROS) that in turn would damage the cellular DNA, proteins and lipids (Wang et al ., 2021). MDA, one of the end products of lipid peroxidation, is thought to be a sensitive marker for reflecting the oxidant status.…”

Section: Discussionmentioning

confidence: 99%

“…SOD catalyzes the dismutation of superoxide anion into hydrogen peroxide, which is later decomposed by CAT into oxygen and water (Yu et al ., 2020). Increased lipid peroxidation might be due to reduction in the activity of SOD, CAT, and GST because these antioxidant enzymes function to protect the cells by diminishing ROS (Wang et al ., 2021). In our study too, Cd treatment with its increasing concentration and exposure duration significantly enhanced the level of MDA in the testicular homogenate.…”

Section: Discussionmentioning

confidence: 99%

Quercetin mediated attenuation of cadmium‐induced oxidative toxicity and apoptosis of spermatogenic cells in caprine testes in vitro

Bhardwaj

Panchal

2021

Environ and Mol Mutagen

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Cadmium (Cd), an environmental toxic heavy metal, has been reported to cause testicular toxicity, which contributes to the recent decline in male fertility worldwide. Quercetin (Qcn), a major dietary antioxidant, has been shown to have protective effects under various pathological conditions. However, whether Qcn provides protection against Cd‐stimulated testicular toxicity remains obscured. The present study was therefore aimed at investigating the ameliorative effect of Qcn supplementation on Cd‐induced toxicity in the goat testis in vitro in a dose‐(10, 50, and 100 μM) and time‐dependent (4 and 8 h) manner. Different cytotoxicity, genotoxicity, and biochemical analyses have been carried out using appropriate methods. Cytotoxicity in testicular cells induced by Cd treatment was apparently mitigated by Qcn treatment, evidenced by decreased apoptotic attributes or frequency in Qcn plus Cd‐treated groups compared to the only Cd‐treated groups. Qcn treatment provides substantial protection to the Cd‐triggered aggression in oxidative (increased MDA levels) and total antioxidant capacity (reduced FRAP activity) in testicular tissue, indicating the anti‐oxidative function of Qcn against Cd exposure. Moreover, Cd‐induced decline in antioxidant status (CAT, SOD, and GST activity) was markedly restored by Qcn supplementation in testicular tissue. In conclusion, this study shows that Qcn treatment significantly attenuated the Cd‐evoked testicular damage, suggesting its beneficial potential in preventing or at least in managing the gonadotoxicity in males induced by steadily increasing Cd contamination in the environment.

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“…Naringenin (Nar) suppresses MDA and H 2 O 2 production and protects the testis from Cd-induced autophagy by downregulating P62 and LC3-II expression. Therefore, Nar protects the testis from Cd-induced toxicity ( Wang et al , 2021 ). Paternal exposure to arsenic results in oxidative stress, autophagy and mitochondrial impairment in the HPG axis of pubertal male offspring.…”

Section: Pre-testicular Processesmentioning

confidence: 99%

Autophagy: a multifaceted player in the fate of sperm

Wang

et al. 2021

Human Reproduction Update

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BACKGROUND Autophagy is an intracellular catabolic process of degrading and recycling proteins and organelles to modulate various physiological and pathological events, including cell differentiation and development. Emerging data indicate that autophagy is closely associated with male reproduction, especially the biosynthetic and catabolic processes of sperm. Throughout the fate of sperm, a series of highly specialized cellular events occur, involving pre-testicular, testicular and post-testicular events. Nonetheless, the most fundamental question of whether autophagy plays a protective or harmful role in male reproduction, especially in sperm, remains unclear. OBJECTIVE AND RATIONALE We summarize the functional roles of autophagy in the pre-testicular (hypothalamic–pituitary–testis (HPG) axis), testicular (spermatocytogenesis, spermatidogenesis, spermiogenesis, spermiation) and post-testicular (sperm maturation and fertilization) processes according to the timeline of sperm fate. Additionally, critical mechanisms of the action and clinical impacts of autophagy on sperm are identified, laying the foundation for the treatment of male infertility. SEARCH METHODS In this narrative review, the PubMed database was used to search peer-reviewed publications for summarizing the functional roles of autophagy in the fate of sperm using the following terms: ‘autophagy’, ‘sperm’, ‘hypothalamic–pituitary–testis axis’, ‘spermatogenesis’, ‘spermatocytogenesis’, ‘spermatidogenesis’, ‘spermiogenesis’, ‘spermiation’, ‘sperm maturation’, ‘fertilization’, ‘capacitation’ and ‘acrosome’ in combination with autophagy-related proteins. We also performed a bibliographic search for the clinical impact of the autophagy process using the keywords of autophagy inhibitors such as ‘bafilomycin A1’, ‘chloroquine’, ‘hydroxychloroquine’, ‘3-Methyl Adenine (3-MA)’, ‘lucanthone’, ‘wortmannin’ and autophagy activators such as ‘rapamycin’, ‘perifosine’, ‘metformin’ in combination with ‘disease’, ‘treatment’, ‘therapy’, ‘male infertility’ and equivalent terms. In addition, reference lists of primary and review articles were reviewed for additional relevant publications. All relevant publications until August 2021 were critically evaluated and discussed on the basis of relevance, quality and timelines. OUTCOMES (i) In pre-testicular processes, autophagy-related genes are involved in the regulation of the HPG axis; and (ii) in testicular processes, mTORC1, the main gate to autophagy, is crucial for spermatogonia stem cell (SCCs) proliferation, differentiation, meiotic progression, inactivation of sex chromosomes and spermiogenesis. During spermatidogenesis, autophagy maintains haploid round spermatid chromatoid body homeostasis for differentiation. During spermiogenesis, autophagy participates in acrosome biogenesis, flagella assembly, head shaping and the removal of cytoplasm from elongating spermatid. After spermatogenesis, through PDLIM1, autophagy orchestrates apical ectoplasmic specialization and basal ectoplasmic specialization to handle cytoskeleton assembly, governing spermatid movement and release during spermiation. In post-testicular processes, there is no direct evidence that autophagy participates in the process of capacitation. However, autophagy modulates the acrosome reaction, paternal mitochondria elimination and clearance of membranous organelles during fertilization. WIDER IMPLICATIONS Deciphering the roles of autophagy in the entire fate of sperm will provide valuable insights into therapies for diseases, especially male infertility.

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Protective effect of naringenin against cadmium-induced testicular toxicity in male SD rats

Cited by 35 publications

References 43 publications

Physiological Roles of Red Carrot Methanolic Extract and Vitamin E to Abrogate Cadmium-Induced Oxidative Challenge and Apoptosis in Rat Testes: Involvement of the Bax/Bcl-2 Ratio

Physiological Roles of Red Carrot Methanolic Extract and Vitamin E to Abrogate Cadmium-Induced Oxidative Challenge and Apoptosis in Rat Testes: Involvement of the Bax/Bcl-2 Ratio

Quercetin mediated attenuation of cadmium‐induced oxidative toxicity and apoptosis of spermatogenic cells in caprine testes in vitro

Autophagy: a multifaceted player in the fate of sperm

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