CHEMOSPHERE
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2018
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IF 4.427
Peng-Cheng Li,Xue-Nan Li,Zheng-Hai Du,Hui Wang,Zhuo-Ran Yu,Jin-Long Li
Di (2-ethyl hexyl) phthalate (DEHP) as a plasticizer can leach away from the plastic and hence entrances into the animal food chain which caused serious hazard in organs of animals, but there are few studies on DEHP kidney toxicity. The heat-shock response (HSR) consisting of the HSPs and HSFs plays an important role in various toxicity stress conditions. To investigate the influence on kidney toxicity and the modulation of HSR during DEHP exposure, female quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. The shrinkages of glomeruli and dilation of kidney tubule epithelia cells were observed in the kidney of DEHP-exposed quail. DEHP treatment could significantly decrease the expressions of HSP25, HSP27, HSP47, HSP60 , while the expressions of HSP10, HSP40, HSP70, HSP90, HSP110 were upregulated in the kidney. In addition, the expression levels of HSF1 and HSF3 were significantly increased under DEHP. This is the first study to demonstrate quail exposure to DEHP is in fact detrimental to bird kidney. Besides, DEHP could attack HSR by affecting the synthesis of HSFs to mediate the transcription of the HSPs resulting in kidney damage.
研究领域:
毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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2025
·Vol. 52
·期 8
·e70050
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IF 2.5
Zibo Xiong,Zhiwei Lai,Sanmu Li,Hua Zhang,Yongqiang Wang,Lishan Tan,Guang Yang,Zuying Xiong
Omeprazole is a widely used proton pump inhibitor and anti‐ Helicobacter pylori drug; however, its nephrotoxicity has been controversial. This study aimed to explore the effects and mechanisms of omeprazole on the kidney. In HK2, HPC, NRK and 293 T cells, omeprazole‐induced alterations in cell morphology, density and viability in a concentration‐dependent manner. Excessively high concentrations (> 50 μM) led to a significant increase in cell death. Interestingly, NRK seemed insensitive to omeprazole. RNA sequencing revealed significant alterations in the genomic expression profile when HK2 cells were incubated at a concentration of 5 μM, including the inhibition of proliferative, metabolic and cytokine receptor gene expression. This alteration augments the environmental susceptibility of HK2 when exposed to H 2 O 2 . Animal studies have shown that omeprazole (10.4 mg/kg × day, 28 days) has no significant effect on body weight, kidney or heart weight or kidney or liver function, as well as plasma calcium and vitamin D. Tissue staining revealed increased expression of the macrophage marker F4/80 in response to omeprazole. In conclusion, therapeutic‐dose omeprazole administration in the short term shows no clinically relevant nephrotoxicity. However, omeprazole decreases cell proliferation and viability by disrupting gene expression; thus, the long‐term use of omeprazole may increase inflammation and environmental susceptibility. These findings provide valuable insights for the clinical use of omeprazole, highlighting the need for careful consideration of its effects in the kidney. Omeprazole decreases cell proliferation and viability by disrupting gene expression; thus, the long‐term use of omeprazole may increase inflammation and environmental susceptibility. These findings provide valuable insights for the clinical use of omeprazole, highlighting the need for careful consideration of its effects in the kidney.
研究领域:
药理学
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毒理学
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分子生物学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 4
·474
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IF 6.6
Jun Hu,Ji Feng,Yan Bai,Zhi-Sheng Yao,Xiao-Yu Wu,Xin-Yu Hong,Guo-Dong Lu,Kun Xue
Background: Sucralose and benzo(a)pyrene (B[a]P) are widespread foodborne substances known to harm human health. However, the effects of their combined exposure on kidney function remain unclear. This study aimed to investigate the mechanisms by which sucralose and B[a]P induce kidney injury through P-glycoprotein (PGP/ABCB1), a crucial protein involved in cellular detoxification. Methods: C57BL/6N mice were co-treated with sucralose and B[a]P for 90 days to evaluate their impact on kidney histopathology and function. In vitro experiments assessed cell viability, reactive oxygen species (ROS) levels, and B[a]P accumulation by flow cytometry. Molecular docking and cellular thermal shift assay (CETSA) were used to determine the binding affinity of sucralose to PGP. Furthermore, PCR, Western blotting, and immunohistochemistry were performed to analyze the expression of PGP and its upstream transcription factors. Results: Ninety days of co-exposure to sucralose and B[a]P significantly exacerbated renal dysfunction in mice, as evidenced by the elevated level of serum creatinine and urea nitrogen, which could be reverted by ROS scavenger N-acetyl cysteine (NAC). In vitro, sucralose promoted cellular accumulation of B[a]P, consequently enhancing B[a]P-induced cell growth inhibition and ROS production. Consistently, B[a]P accumulation was enhanced by PGP knockdown in both HK2 and HEK-293 cells. Mechanistically, sucralose can directly bind to PGP, competitively inhibiting its efflux capacity and increasing intracellular B[a]P retention. Prolonged co-exposure further downregulated PGP expression, possibly through the reductions of its transcriptional regulators (PXR,NRF2, andNF-κB). Conclusions: Co-exposure to sucralose and B[a]P exacerbates renal injury by impairing PGP function. Mechanistically, sucralose inhibits PGP activity, resulting in the accumulation of B[a]P within renal cells. This accumulation triggers oxidative stress and inhibits cell growth, which demonstrates that sucralose potentiates B[a]P-induced nephrotoxicity by directly inhibiting PGP-mediated detoxification pathways, thus underscoring the critical need to evaluate toxicity risks associated with combined exposure to these compounds.
研究领域:
毒理学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2019
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IF 3.298
Qiaojian Zhang,Shufang Zheng,Shengchen Wang,Wei Wang,Houjuan Xing,Shiwen Xu
Chlorpyrifos (CPF) has become a mainly pollution in water environment. Micro-RNAs (miRNAs) play an important part in the development of apoptosis and autophagy. However, the potential mechanism of CPF induced kidney toxicity and the roles of miRNAs are still unclear. To explore the underlying mechanism, the kidney of common carp exposed to different concentrations of CPF for 40 days was used as a research object. We found that CPF could damage the ultrastructure and function of kidney; and also caused antioxidant system disorder. CPF inhibited the mRNA level of miR-19a which improved AMP-activated protein kinase (AMPK). Furthermore, the detection of apoptosis and autophagy relative genes showed that the expressions of TSC complex subunit 2 (TSC2), light chain 3 (LC3), Dynein, tumor protein 53 (p53), Bcl-2 associated X protein (Bax), caspase-3 and caspase-9 were enhanced and the expressions of nechanistic target of rapamycin (mTOR), Ras homolog mTORC1 binding (Rheb) and B-cell lymphoma (Bcl-2) were reduced in dose-dependent way. Taken together, we conclude that CPF causes oxidative stress and miR-19a-AMPK axis disorder, thereby promotes apoptosis and autophagy in common carp kidney. Our study will provide theoretical basis for toxicology research and environmental protection of CPF.
研究领域:
毒理学
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环境科学
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分子生物学
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水生生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Lingjiao Li,Chengyao Feng,Wenchao Zhang,Lin Qi,Binfeng Liu,Hua Wang,Chenbei Li,Zhihong Li,Chao Tu,Wenhu Zhou
Cisplatin, a frontline chemotherapeutic agent against cancer, faces challenges in clinical application due to significant toxicities and suboptimal efficacy. Renal toxicity, a dose-limiting factor of cisplatin, results from multifactorial processes including cisplatin-induced cellular pyroptosis, oxidative damage, and inflammatory responses. Our findings reveal that Tea Polyphenols Nanoparticles (TPNs) derived from Epigallocatechin gallate (EGCG) effectively could address these diverse mechanisms, comprehensively alleviating cisplatin-induced nephrotoxicity. Leveraging TPNs as carriers, chemical conjugation enables the encapsulation of tetravalent cisplatin prodrug, extending its systemic half-life, enhancing tumor tissue accumulation, while simultaneously mitigating renal toxicity. Concurrently, employing a CRISPR/Cas9 kinase library, we identified CSNK2A1 as a target sensitizing tumor cells to cisplatin, enabling specific siRNA sequences to augment cisplatin susceptibility, thereby minimizing the dosage requirement. Benefiting from the versatile carrier properties of TPNs to codeliver cisplatin prodrug and anti-CSNK2A1 siRNA, we developed a codelivery system, Pt-TPNs/siRNA. Pt-TPNs/siRNA not only enhances the anticancer effects but also mitigates cisplatin-induced renal toxicity, achieving efficacy while reducing toxicity. Mechanistic and safety assessments of these nanoparticles were conducted at both cellular and animal levels, opening new avenues for improved clinical utilization of cisplatin.
研究领域:
肿瘤学
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药理学
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纳米技术
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分子生物学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
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