Ketotifen counteracts cisplatin-induced acute kidney injury in mice via targeting NF- κ B/NLRP3/Caspase-1 and Bax/Bcl2/Caspase-3 signaling pathways

被引:1
|
作者
Mohtadi, Shokooh [1 ,2 ,3 ]
Salehcheh, Maryam [1 ,2 ]
Tabandeh, Mohammad Reza [4 ,5 ]
Khorsandi, Layasadat [6 ]
Khodayar, Mohammad Javad [1 ,2 ]
机构
[1] Ahvaz Jundishapur Univ Med Sci, Med Basic Sci Res Inst, Toxicol Res Ctr, Ahvaz, Iran
[2] Ahvaz Jundishapur Univ Med Sci, Fac Pharm, Dept Toxicol, Ahvaz, Iran
[3] Ahvaz Jundishapur Univ Med Sci, Student Res Comm, Ahvaz, Iran
[4] Shahid Chamran Univ Ahvaz, Fac Vet Med, Dept Basic Sci, Div Biochem & Mol Biol, Ahvaz, Iran
[5] Shahid Chamran Univ Ahvaz, Stem Cells & Transgenic Technol Res Ctr, Ahvaz, Iran
[6] Ahvaz Jundishapur Univ Med Sci, Med Basic Sci Res Inst, Cellular & Mol Res Ctr, Ahvaz, Iran
关键词
Cisplatin; Ketotifen; Nephrotoxicity; Oxidative stress; NLRP3; inflammasome; Apoptosis; INDUCED NEPHROTOXICITY; OXIDATIVE STRESS; INHIBITION; MECHANISMS; EXPRESSION; MOLECULE-1; ALPHA; ACID; INFLAMMATION; GLUTATHIONE;
D O I
10.1016/j.biopha.2024.116797
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cisplatin (CIS) stands as one of the most effective chemotherapy drugs currently available. Despite its anticancer properties, the clinical application of CIS is restricted due to nephrotoxicity. Our research aimed to specify the impact of ketotifen fumarate (KET) against nephrotoxicity induced by CIS in mice. Male NMRI mice were treated with KET (0.4, 0.8, and 1.6 mg/kg, ip) for seven days. On the fourth day of the study, a single dose of CIS (13 mg/ kg, ip) was administered, and the mice were sacrificed on the eighth day. The results indicated that administration of KET attenuated CIS-induced elevation of BUN and Cr in the serum, as well as renal KIM-1 levels. This improvement was accompanied by a significant reduction in kidney tissue damage, which was supported by histopathological examinations. Likewise, the decrease in the ratio of GSH to GSSG and antioxidant enzyme activities (CAT, SOD, and GPx), and the increase in lipid peroxidation marker (TBARS) were reversed in KETtreated mice. The ELISA results revealed that KET-treated mice ameliorated CIS-induced elevation in the renal levels of TNF-alpha, IL-1 beta, and IL-18. Western blot analysis exhibited that KET suppressed the activation of the transcription factor NF-kappa B and the NLRP3 inflammasome in the kidney of CIS-treated mice. Moreover, KET treatment reversed the changes in the protein expression of markers related to apoptosis (Bax, Bcl2, Caspase-3, and p53). Interestingly, KET significantly enhanced the cytotoxicity of CIS in HeLa cells. In conclusion, this study provides valuable insights into the promising effects of KET in mitigating CIS-induced nephrotoxicity.
引用
收藏
页数:14
相关论文
共 50 条
  • [31] NLRP3 Inflammasome Knockout Mice Are Protected against Ischemic but Not Cisplatin-Induced Acute Kidney Injury
    Kim, Hyun-Jung
    Lee, Dong Won
    Ravichandran, Kameswaran
    Keys, Daniel O.
    Akcay, Ali
    Quocan Nguyen
    He, Zhibin
    Jani, Alkesh
    Ljubanovic, Danica
    Edelstein, Charles L.
    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2013, 346 (03): : 465 - 472
  • [32] HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells
    Feng Yao
    Zhen Jin
    Zihan Zheng
    Xiaohan Lv
    Lingxuan Ren
    Jianjun Yang
    Danli Chen
    Bo Wang
    Wei Yang
    Lifang Chen
    Weirong Wang
    Jianli Gu
    Rong Lin
    Cell Death Discovery, 8
  • [33] HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells
    Yao, Feng
    Jin, Zhen
    Zheng, Zihan
    Lv, Xiaohan
    Ren, Lingxuan
    Yang, Jianjun
    Chen, Danli
    Wang, Bo
    Yang, Wei
    Chen, Lifang
    Wang, Weirong
    Gu, Jianli
    Lin, Rong
    CELL DEATH DISCOVERY, 2022, 8 (01)
  • [34] PM2.5-induced pulmonary inflammation via activating of the NLRP3/caspase-1 signaling pathway
    Jia, Hui
    Liu, Yang
    Guo, Dan
    He, Wei
    Zhao, Long
    Xia, Shuyue
    ENVIRONMENTAL TOXICOLOGY, 2021, 36 (03) : 298 - 307
  • [35] Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury
    Liu, Yuping
    Fang, Qing
    Ming, Tingqian
    Zuo, Jing
    Jing, Guoqing
    Song, Xuemin
    CLINICAL AND EXPERIMENTAL NEPHROLOGY, 2023, 27 (09) : 781 - 790
  • [36] Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury
    Yuping Liu
    Qing Fang
    Tingqian Ming
    Jing Zuo
    Guoqing Jing
    Xuemin Song
    Clinical and Experimental Nephrology, 2023, 27 : 781 - 790
  • [37] Amantadine reduces sepsis-induced brain injury via NLRP3/ caspase-1 inflammasome activation
    Karabacak, Pinar
    Bindal, Ahmet
    Ozcan, Mustafa Soner
    Ilhan, Ilter
    Tepebasi, Muhammet Yusuf
    Arlioglu, Melih
    Taner, Rumeysa
    Asci, Halil
    IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 2025, 28 (05) : 620 - 626
  • [38] Luteolin enhanced antioxidant capability and induced pyroptosis through NF-κB/NLRP3/Caspase-1 in splenic lymphocytes exposure to ammonia
    Chen, Dechun
    Shen, Fanyu
    Liu, Jiahao
    Tang, Haojinming
    Teng, Xiaohua
    Yang, Falong
    Liu, Haifeng
    SCIENCE OF THE TOTAL ENVIRONMENT, 2024, 919
  • [39] NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1
    Qi, Jie
    Yu, Xiao-Jing
    Shi, Xiao-Lian
    Gao, Hong-Li
    Yi, Qiu-Yue
    Tan, Hong
    Fan, Xiao-Yan
    Zhang, Yan
    Song, Xin-Ai
    Cui, Wei
    Liu, Jin-Jun
    Kang, Yu-Ming
    CARDIOVASCULAR TOXICOLOGY, 2016, 16 (04) : 345 - 354
  • [40] NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1
    Jie Qi
    Xiao-Jing Yu
    Xiao-Lian Shi
    Hong-Li Gao
    Qiu-Yue Yi
    Hong Tan
    Xiao-Yan Fan
    Yan Zhang
    Xin-Ai Song
    Wei Cui
    Jin-Jun Liu
    Yu-Ming Kang
    Cardiovascular Toxicology, 2016, 16 : 345 - 354