Journal of Environmental Sciences
·
2025
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IF 6.3
Hongfei Hu,Guangji Wei,Hai Lan,Yang Feng,Shihua Luo,Yaqin Pang,Yanxin Huang,Huixiong Yuan,Huixin Peng,Wencheng Chen
The liver, a critical metabolic organ, is particularly vulnerable to damage upon aluminum exposure. However, the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated. This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue. The results indicated that AlCl 3 exposure induced significant liver dysfunction, characterized by reduced adenosine triphosphate levels, elevated plasma alanine aminotransferase and aspartate aminotransferase. Histopathological analysis of liver tissue revealed marked histological damage, accompanied by substantial iron deposition. Further examinations demonstrated elevated hepatic levels of malondialdehyde, 4-hydroxynonenal, and reactive oxygen species, decreased levels of glutathione (GSH) and superoxide dismutase, increased levels of Oxidized glutathione (GSSG), and a reduced GSH/GSSG ratio. The mRNA and protein expression of ferroptosis-related molecules, including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11, were significantly downregulated, while acyl-CoA synthetase long-chain family member 4, ferritin heavy chain 1, and iron regulatory protein 1 levels were significantly upregulated. Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage, attenuating signs of ferroptosis. These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.
研究领域:
毒理学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2023
·Vol. 202
·期 7
·3180-3192
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IF 3.9
Nong Weihua,Wei Gaomeng,Wang Junli,Lei Xiaocan,Wang Jinyuan,Wei Yanhong,Dong Mingyou,He Liqiao
This study aimed to investigate the protective effect of nicotinamide mononucleotide (NMN) on testicular spermatogenesis in aluminum chloride (AlCl 3 )-exposed rats and to elucidate the potential underlying mechanism. The results indicated that AlCl 3 -induced testicular damage, leading to reduced sperm quality, increased apoptosis, decreased cell proliferation, and impaired Sertoli cell function in rats. Additionally, glycolytic metabolism was observed to be hindered. However, after NMN treatment, there was a noticeable improvement in testicular damage among the rats, marked by increased sperm quality, reduced apoptosis, enhanced cell proliferation, improved Sertoli cell function, and an activated glycolytic metabolism. The findings of this study suggest that NMN alleviates testicular spermatogenesis impairment induced by AlCl 3 exposure through the inhibition of spermatogenic cell apoptosis, promotion of spermatogenic cell proliferation, and activation of glycolytic pathways. The study contributes an experimental foundation for potential future clinical applications of NMN in cases of AlCl 3 -exposed spermatogenic dysfunction.
研究领域:
生殖生物学
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毒理学
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代谢生物学
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DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
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IF 8.2
Wei Guangji,Peng Huixin,Hu Hongfei,Lan Hai,Feng Yang,Luo Shihua,Huang Yanxin,Yuan Huixiong,Chen Wencheng
Aluminum (Al) is a pervasive environmental contaminant with detrimental biological effects. Although Al exposure induces oxidative stress and toxicity in spermatogenic cells, leading to impaired male reproductive function, the underlying molecular mechanisms remain incompletely elucidated. In this study, we systematically evaluated the toxic effects of Al on spermatogenic cells using both in vivo and in vitro models. Transcriptomic profiling of GC-2spd cells revealed Al-induced differential gene expression related to oxidative stress response, iron homeostasis, and lipid metabolism regulation. These alterations were notably enriched in the ferroptosis and HIF-1 signaling pathways. Subsequent in vivo analyses demonstrated that Al exposure increased iron levels and oxidative stress while reducing ATP content in mouse testes, resulting in testicular damage, decreased sperm quality, and lowered serum sex hormone levels, all of which contribute to reproductive dysfunction. Further investigations confirmed that Al disrupts redox and iron homeostasis, promoting lipid peroxidation and ferroptosis in both mouse testes and GC-2spd cells. Importantly, administration of the ferroptosis inhibitor Ferrostatin-1 (Fer-1) effectively restored homeostasis, thereby alleviating Al-induced ferroptosis and spermatogenic cell toxicity. In conclusion, this study demonstrates that Al disrupts iron and redox balance, leading to iron accumulation and lipid peroxidation in spermatogenic cells, which triggers ferroptosis and ultimately causes male reproductive impairment. These findings identify ferroptosis as a novel therapeutic target for mitigating aluminum-related reproductive risks and provide a scientific basis for public health interventions in occupational and environmental settings grounded in this newly characterized cell death mechanism.
研究领域:
毒理学
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生殖生物学
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分子细胞生物学
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环境医学
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氧化应激
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金属毒理
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细胞死亡机制
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）