Selenium alleviates lead-induced CIK cells pyroptosis and inflammation through IRAK1/TAK1/IKK pathway

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 142, P. 109101 - 109101

Published: Sept. 26, 2023

Language: Английский

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Fluoride induces pyroptosis via IL-17A-mediated caspase-1/11-dependent pathways and Bifidobacterium intervention in testis

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 926, P. 172036 - 172036

Published: March 28, 2024

Language: Английский

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Lead Causes Lipid Droplet Accumulation by Impairing Lysosomal Function and Autophagic Flux in Testicular Sertoli Cells

Toxics, Journal Year: 2025, Volume and Issue: 13(3), P. 175 - 175

Published: Feb. 28, 2025

Lead (Pb) is one of the most common environmental pollutants that negatively impacts male reproductive health. Thus far, underlying molecular mechanisms Pb-induced toxicity are still not well understood. In this study, 64 ICR mice were given drinking water with Pb (0, 100, 200, and 300 mg/L) for 90 days. We found exposure to mg/L resulted in reduced sperm quality elevated autophagy-related protein levels mouse testes. Our findings indicate hindered autophagic clearance by impairing lysosomes’ function then obstructing fusion lysosomes autophagosomes. The autophagy cycle obstruction prevented lipid droplets from breakdown led their accumulation Sertoli cells. turn, ccytotoxic effects interruption maturation stage, instead elongation phase, could be alleviated either Chloroquine or Bafilomycin A1. Furthermore, 400 μM initiated TFE3 nuclear translocation caused increased expression its target genes. Then, knockdown formation autophagosome. addition, use antioxidant NAC notably enhanced activity occurrence This study demonstrated disrupted flow, which droplet TM4 Consequently, focusing on stage might offer a potential therapeutic approach alleviate exposure.

Language: Английский

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Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3496 - 3496

Published: April 8, 2025

Male infertility is intricately linked to dysregulated cell death pathways, including ferroptosis, cuproptosis, pyroptosis, and autophagy. Ferroptosis, driven by iron-dependent lipid peroxidation through the Fenton reaction inactivation of GPX4/Nrf2/SLC7A11 axis, disrupts spermatogenesis under conditions oxidative stress, environmental toxin exposure, or metabolic disorders. Similarly, cuproptosis—characterized mitochondrial dysfunction disulfide stress due copper overload—exacerbates germ apoptosis via FDX1 activation NADPH depletion. Pyroptosis, mediated NLRP3 inflammasome gasdermin D, amplifies testicular inflammation loss IL-1β/IL-18 release, particularly in response insults. Autophagy maintains homeostasis clearing damaged organelles proteins; however, its dysregulation impairs sperm maturation compromises blood–testis barrier integrity. These pathways intersect shared regulators; reactive oxygen species mTOR modulate autophagy–pyroptosis balance, while Nrf2 bridge ferroptosis–cuproptosis crosstalk. Therapeutic interventions targeting these mechanisms have shown promise preclinical models. However, challenges persist, tissue-specific roles isoforms, off-target effects pharmacological inhibitors, transgenerational epigenetic impacts toxins. This review synthesizes current molecular insights into implicated male infertility, emphasizing their interplay translational potential for restoring spermatogenic function.

Language: Английский

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Multifaceted Impacts of Monosodium Glutamate on Testicular Health: Insights into Pyroptosis and Therapeutic Potential of Resveratrol

Folia Morphologica, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Background: Monosodium glutamate was considered one of the food additive and flavor enhancer in processed meat soup that affects testicular tissues, aim this research to investigates impact monosodium (MSG) on structure rats explores potential protective effects resveratrol. Material Methods: Four experimental groups involved our study 10 each.: first group as control group; second (Resveratrol group: received 20 mg/kg resveratrol, via oral gavage); third (MSG with a dose 60 body weight daily, gastric tube, fourth (MSG+ Resveratrol group). Serum level testosterone, FSH, LH, were measured. Testicular tissues prepared for measurement oxidative stress markers, gene expression NLRP3, Caspase 3, GSK-3β. Moreover, paraffin blocks contained tissue used histological immunohistochemical examination. Additionally, seminal smear from epididymis examined. Results: MSG administration adversely affected testosterone production, hormonal levels, sperm parameters, Histological examination revealed marked degeneration, assessments indicated elevated MDA lipid peroxidation marker decrease SOD, CAT antioxidant enzymes. MSG-induced apoptotic pyroptotic markers its expressions. Importantly. Administration resveratrol reversed detrimental MSG, demonstrating corrective influence hypothalamic–pituitary–gonadal axis disruption, improvement attenuation stress, anti-apoptotic activity, anti-pyroptotic effects. The Ki-67 cell proliferation further supported positive response spermatogenesis dysfunction upon treatment. Conclusions: This comprehensive exploration sheds light effect against mechanistic role.

Language: Английский

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Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-β1/Smad2/3 pathways: the role of Isochlorogenic acid a

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(3)

Published: May 1, 2024

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), phenolic present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity ICR mice. An evaluation performed on oxidative stress, inflammation fibrosis, related signaling. The results indicate that attenuates abnormal liver function. reduced stress caused by Pb. abated fibrosis decreased inflammatory cytokines interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNF-α). abrogated reductions activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Masson staining revealed collagen fiber deposition fibrotic livers. Western blot immunohistochemistry analyses showed increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. also expression I, α-smooth muscle actin (α-SMA), extracellular signal-regulated (p-ERK), c-jun N-terminal (p-JNK), p-p38, signal transducer activator transcription 3 (p-STAT3), transforming growth factor β1 (TGF-β1), p-Smad2/3 livers Overall, ameliorates hepatitis inhibiting AMPK/MAPKs/NF-κB STAT3/TGF-β1/Smad2/3 pathways.

Language: Английский

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Novel findings from arsenic‑lead combined exposure in mouse testicular TM4 Sertoli cells based on transcriptomics

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 913, P. 169611 - 169611

Published: Dec. 27, 2023

Language: Английский

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Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-β1/Smad2/3 pathways: the role of Isochlorogenic acid A

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 9, 2024

Abstract Pb is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), phenolic present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity mice. We divided five groups ICR mice into control experimental treated them for three months. The group received normal diet, while consumed lead-containing water (1 g/L lead acetate) with or without ICAA. An evaluation performed on oxidative stress, inflammation fibrosis, related signaling. results indicate that attenuates abnormal liver function. reduced stress caused by Pb. abated fibrosis decreased inflammatory cytokines interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNF-α). abrogated reductions activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Masson stain staining revealed collagen fiber deposition fibrotic livers. Western blot immunohistochemistry analyses showed increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. also expression I, α-smooth muscle actin (α-SMA), extracellular signal-regulated (p-ERK), c-jun N-terminal (p-JNK), p-p38, signal transducer activator transcription 3 (p-STAT3), transforming growth factor β1 (TGF-β1), p-Smad2/3 livers Overall, ameliorates hepatitis inhibiting AMPK/MAPKs/NF-κB STAT3/TGF-β1/Smad2/3 pathways.

Language: Английский

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The Association between Multiple Metal Exposure and Semen Quality: Shanghai, China

Published: Jan. 1, 2023

There is still no solid evidence linking metal exposure to the quality of human sperm. insufficient and inconsistent data on how metals affect semen quality. To explore association between multi-metals parameters volunteers in Shanghai Human Sperm Bank with a cross-sectional study. A sample was collected analyzed after two days abstinence, At same time, Urine samples were 29 classes concentrations detected. We used five models evaluate: (1) relationship different classes' urine levels parameters; (2) mix-effects urinary parameters. Urinary lead, manganese, copper, beryllium negatively associated normal sperm morphology (β=-1.82, 95% CI: -2.88, -0.76; β=-0.79，95% -1.56, -0.01; β=-2.15; -3.42, -0.88; β=-0.32, -0.63, -0.01, respectively); manganese correlated progressive motility (β=-3.54, -6.89, -0.19), In addition, Magnesium zinc significantly positively concentration (β=8.76, 0.90, 17.35; β=9.53, 1.41, 18.29, respectively), total count (β=13.43, 2.63, 25.36; β=11.07，95% 0.40,23.00, respectively). conclusion, poor higher including while magnesium better

Language: Английский

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