The reno-protective effect of Empagliflozin against carbon tetrachloride (CCl4)-induced nephrotoxicity in mice halting JNK/MKK4/NRF2/NF-KB pathway

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-04-07 DOI:10.1016/j.fct.2025.115439

Amany A. Alzokaky , Shimaa K. Saber , Mennatallah O. Zaki

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引用次数: 0

Abstract

Aim

This study designed to evaluate the reno-protective effects of Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, against carbon tetrachloride (CCl4)-induced nephrotoxicity in mice targeting JNK/MKK4/NRF2/NF-KB pathway.

Methods

Male albino mice were given EMPA (10 mg/kg, orally) for 4 weeks prior to a single i.p. injection of 10 % CCl4 (20 ml/kg). Mice were sacrificed 48 h post CCl4 injection.

Key findings

EMPA attenuated CCl4-induced renal injury, as reflected by a decrease in serum urea and creatinine levels, also preserved the histological integrity of kidney tissue. Theses reno-protective effects of EMPA can be mainly due to its 1. Antioxidant, (↑CAT, ↑SOD, ↑Nrf-2 and ↑ARE), 2. Anti-inflammatory (↓NF-κB and ↓TNF-α) and 3. Anti-apoptotic (↓Caspase-3) proprieties. EMPA also inhibited JNK/MKK4 signaling pathway, which plays a critical role in kidney damage.

Conclusion

These finding confirm the reno-protective effect of EMPA with a modulatory impact on JNK/MKK4/Nrf2/NF-κB signaling network; suggesting its therapeutic utility to minimize acute kidney injury (AKI) in clinical setting in the future.

Abstract Image

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Empagliflozin阻止JNK/MKK4/NRF2/NF-KB通路对四氯化碳（CCl4）诱导的小鼠肾毒性的肾保护作用

目的研究钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂恩帕列净（EMPA）对四氯化碳（CCl4）诱导的小鼠肾毒性靶向JNK/MKK4/NRF2/NF-KB通路的肾保护作用。方法白化病小鼠口服EMPA （10 mg/kg，口服）4周后，单次滴注10% CCl4 （20 ml/kg）。注射CCl4 48 h后处死小鼠。主要发现sempa减轻ccl4诱导的肾损伤，反映在血清尿素和肌酐水平的降低，并保持肾组织的组织学完整性。EMPA的这些保护作用主要是由于它的1。抗氧化剂，（↑CAT，↑SOD，↑Nrf-2和↑ARE）， 2。2 .抗炎（↓NF-κB和↓TNF-α）；抗凋亡（↓Caspase-3）特性。EMPA还抑制JNK/MKK4信号通路，该信号通路在肾损伤中起关键作用。结论EMPA对JNK/MKK4/Nrf2/NF-κB信号网络具有一定的调节作用；提示其在减少急性肾损伤（AKI）的临床应用前景。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.