Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells

Li, Quanwei; Yang, Qingwen; Guo, Pengyi; Feng, Ying; Wang, Shaofeng; Guo, Jianying; Tang, Zhaoxin; Yu, Wenli; Liao, Jianzhao

doi:10.1016/j.fct.2023.113950

Cited by 7 publications

(5 citation statements)

References 70 publications

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“…Dietary supplementation of appropriate amount of Zn can not only improve animal reproductive performance and maintain intestinal microenvironment homeostasis, but also improve antioxidant function and enhance immunity. However, excessive intake of Zn in animals can lead to decreased antioxidant function, resulting in oxidative stress and programmed death ( Yang et al., 2022 ; Li et al., 2023b ). It has been proved that the kidney is an important target organ for Zn toxicity, but its pathogenic mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine

Yang,

Qian,

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionZinc (Zn) is an essential trace element in animals, but excessive intake can lead to renal toxicity damage. Thus, the exploration of effective natural antagonists to reduce the toxicity caused by Zn has become a major scientific problem.MethodsHere, we found that hesperidin could effectively alleviate the renal toxicity induced by Zn in pigs by using hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, fluorescence quantitative PCR, and microfloral DNA sequencing.ResultsThe results showed that hesperidin could effectively attenuate the pathological injury in kidney, and reduce autophagy and apoptosis induced by Zn, which evidenced by the downregulation of LC3, ATG5, Bak1, Bax, Caspase-3 and upregulation of p62 and Bcl2. Additionally, hesperidin could reverse colon injury and the decrease of ZO-1 protein expression. Interestingly, hesperidin restored the intestinal flora structure disturbed by Zn, and significantly reduced the abundance of Tenericutes (phylum level) and Christensenella (genus level).DiscussionThus, altered intestinal flora and intestinal barrier function constitute the gut-kidney axis, which is involved in hesperidin alleviating Zn-induced nephrotoxicity. Our study provides theoretical basis and practical significance of hesperidin for the prevention and treatment of Zn-induced nephrotoxicity through gut-kidney axis.

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Section: Discussionmentioning

confidence: 99%

Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine

Yang,

Qian,

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Zinc’s role in ferroptosis has been demonstrated in various studies, with zinc oxide nanoparticles (ZONPs) showing potential in cervical and breast cancer treatment ( Chen J. et al, 2021 ; Li Q. et al, 2023 ). In cervical cancer, ZONPs not only induce lipid ROS and malondialdehyde (MDA) production but also suppress CD164 by enhancing miR-505-3p levels ( Lei et al, 2022 ).…”

Section: Types Of Nanoparticles Capable Of Inducing Ferroptosis In Ca...mentioning

confidence: 99%

Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution

Adzavon,

Zhao,

et al. 2024

Front. Pharmacol.

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Ferroptosis is a form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. Ferroptosis is currently proposed as one of the most promising means of combating tumor resistance. Nevertheless, the problem of ferroptosis resistance in certain cancer cells has been identified. This review first, investigates the mechanisms of ferroptosis induction in cancer cells. Next, the problem of cancer cell resistance to ferroptosis, as well as the underlying mechanisms is discussed. Recently discovered ferroptosis-suppressing biomarkers have been described. The various types of nanoparticles that can induce ferroptosis are also discussed. Given the ability of nanoparticles to combine multiple agents, this review proposes nanoparticle-based ferroptosis cell death as a viable method of circumventing this resistance. This review suggests combining ferroptosis with other forms of cell death, such as apoptosis, cuproptosis and autophagy. It also suggests combining ferroptosis with immunotherapy.

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“…Ferritinophagy mediated by NCOA4 promotes ferritin degradation and iron release, thereby increasing free iron content and further inducing ferroptosis [ 97 ]. In a zinc-induced porcine model of testicular dysfunction, zinc induces ferroptosis by regulating mitochondrial autophagy [ 98 ]. Hexavalent chromium also causes testicular autophagy and ferroptosis in rats [ 99 ].…”

Section: Ferroptosis-related Biological Responses In Testicular Injurymentioning

confidence: 99%

“…In addition, classical ferroptosis activators (such as ML-210) or inhibitors (such as ferrostatin-1, Fer-1) modulate intracellular autophagic flux in testicular injury. Similarly, an autophagy inhibitor, 3-methyladenine, has been shown to alleviate testicular ferroptosis [ 98 , 99 ]. Two sides of autophagy have been revealed in the study of testicular injury induced by copper sulfate.…”

Section: Ferroptosis-related Biological Responses In Testicular Injurymentioning

confidence: 99%

“…Arsenite has been shown to induce oxidative stress, lipid peroxidation, mitochondrial dysfunction, and ferroptosis in the testis, indicating arsenite triggers testicular cell death by inducing ferroptosis [ 84 ]. A recent study has demonstrated that mitophagy also contributes to zinc-induced ferroptosis in porcine testis cells, providing new insights into heavy metal toxicology [ 98 ].…”

Section: Ferroptosis In Male Reproductive Dysfunctionmentioning

confidence: 99%

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Emerging roles of ferroptosis in male reproductive diseases

Yuan,

Sun,

et al. 2023

Cell Death Discov.

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Ferroptosis is a type of programmed cell death mediated by iron-dependent lipid peroxidation that leads to excessive lipid peroxidation in different cells. Ferroptosis is distinct from other forms of cell death and is associated with various diseases. Iron is essential for spermatogenesis and male reproductive function. Therefore, it is not surprising that new evidence supports the role of ferroptosis in testicular injury. Although the molecular mechanism by which ferroptosis induces disease is unknown, several genes and pathways associated with ferroptosis have been linked to testicular dysfunction. In this review, we discuss iron metabolism, ferroptosis, and related regulatory pathways. In addition, we analyze the endogenous and exogenous factors of ferroptosis in terms of iron metabolism and testicular dysfunction, as well as summarize the relationship between ferroptosis and male reproductive dysfunction. Finally, we discuss potential strategies to target ferroptosis for treating male reproductive diseases and provide new directions for preventing male reproductive diseases.

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Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells

Cited by 7 publications

References 70 publications

Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine

Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine

Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution

Emerging roles of ferroptosis in male reproductive diseases

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