Acetovanillone augmented the cardioprotective effect of carvedilol against cadmium-induced heart injury via suppression of oxidative stress and inflammation signaling pathways

被引:0
作者
Emad H. M. Hassanein
Adel G. Bakr
Ehab A. M. El-Shoura
Lamiaa Khalaf Ahmed
Fares E. M. Ali
机构
[1] Al-Azhar University,Department of Pharmacology and Toxicology, Faculty of Pharmacy
[2] Al-Azhar University,Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls)
[3] Al-Azhar University,Department of Pharmacology and Toxicology, Faculty of Pharmacy
来源
Scientific Reports | / 13卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Cardiac toxicity is a public health issue that can be caused by both environmental and occupational exposures. The current study aimed to investigate the effectiveness of carvedilol (CV), Acetovanillone (ACET), and their combination for ameliorating cadmium (Cd)-induced oxidative stress, inflammation, and necroptosis. Rats were assigned to; the normal group, Cd group (2 mg/kg; i.p., single dose), and the other three groups received orally CV (10 mg/kg), ACET (25 mg/kg), and CV plus ACET, respectively and a single dose of Cd. Oral administration of CV, ACET, and their combination significantly dampens cardiac oxidative injury by increasing antioxidants GSH and SOD levels, while it decreases MDA and NADPH oxidase levels mediated by decreasing cardiac abundance of Nrf2, HO-1, and SIRT1 and downregulating KEAP-1 and FOXO-3 levels. Also, they significantly attenuated inflammatory response as indicated by reducing MPO and NOx as well as proinflammatory cytokines TNF-α and IL-6 mediated by downregulating TLR4, iNOS, and NF-κB proteins expression as well as IκB upregulation. Moreover, they potently counteracted cardiac necroptosis by downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins expression. Of note, the combination of CV and ACET have marked protection that exceeded each drug alone. Conclusively, CV ad ACET potently mitigated Cd-induced cardiac intoxication by regulating NADPH oxidase, KEAP-1/Nrf2/HO-1, SIRT1/FOXO-3, TLR4/NF-κB/iNOS, and RIPK1/RIPK3/MLKL signals.
引用
收藏
相关论文
共 50 条
[41]   Protective Effects of Astilbin Against Cadmium-Induced Apoptosis in Chicken Kidneys via Endoplasmic Reticulum Stress Signaling Pathway [J].
Xiuyu Li ;
Ming Ge ;
Weifeng Zhu ;
Panpan Wang ;
Jiangfeng Wang ;
Tiange Tai ;
Yuxi Wang ;
Jianxu Sun ;
Guangliang Shi .
Biological Trace Element Research, 2022, 200 :4430-4443
[42]   Protective Effects of Astilbin Against Cadmium-Induced Apoptosis in Chicken Kidneys via Endoplasmic Reticulum Stress Signaling Pathway [J].
Li, Xiuyu ;
Ge, Ming ;
Zhu, Weifeng ;
Wang, Panpan ;
Wang, Jiangfeng ;
Tai, Tiange ;
Wang, Yuxi ;
Sun, Jianxu ;
Shi, Guangliang .
BIOLOGICAL TRACE ELEMENT RESEARCH, 2022, 200 (10) :4430-4443
[43]   Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats [J].
Ansari, Mohd Nazam ;
Ganaie, Majid A. ;
Rehman, Najeeb Ur ;
Alharthy, Khalid M. ;
Khan, Tajdar H. ;
Imam, Faisal ;
Ansari, Mushtaq A. ;
Al-Harbi, Naif O. ;
Jan, Basit L. ;
Sheikh, Ishfaq A. ;
Hamad, Abubaker M. .
SAUDI PHARMACEUTICAL JOURNAL, 2019, 27 (05) :673-681
[44]   Cardioprotective Effect of Gossypin Against Myocardial Ischemic/Reperfusion in Rats via Alteration of Oxidative Stress, Inflammation and Gut Microbiota [J].
Cheng, Gong ;
Zhang, Ji ;
Jia, Shuo ;
Feng, Panpan ;
Chang, Fengjun ;
Yan, Li ;
Gupta, Pranay ;
Wu, Haoyu .
JOURNAL OF INFLAMMATION RESEARCH, 2022, 15 :1637-1651
[45]   A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative Damage [J].
Raktim Mukherjee ;
Sudeep Banerjee ;
Niraj Joshi ;
Prem Kumar Singh ;
Darshee Baxi ;
A. V. Ramachandran .
Cardiovascular Toxicology, 2011, 11 :78-88
[46]   A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative Damage [J].
Mukherjee, Raktim ;
Banerjee, Sudeep ;
Joshi, Niraj ;
Singh, Prem Kumar ;
Baxi, Darshee ;
Ramachandran, A. V. .
CARDIOVASCULAR TOXICOLOGY, 2011, 11 (01) :78-88
[47]   Protective role of curcumin in cadmium-induced testicular injury in mice by attenuating oxidative stress via Nrf2/ARE pathway [J].
Yang, Shu-Hua ;
He, Jian-Bin ;
Yu, Li-Hui ;
Li, Lin ;
Long, Miao ;
Liu, Ming-Da ;
Li, Peng .
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 2019, 26 (33) :34575-34583
[48]   Protective role of curcumin in cadmium-induced testicular injury in mice by attenuating oxidative stress via Nrf2/ARE pathway [J].
Shu-Hua Yang ;
Jian-Bin He ;
Li-Hui Yu ;
Lin Li ;
Miao Long ;
Ming-Da Liu ;
Peng Li .
Environmental Science and Pollution Research, 2019, 26 :34575-34583
[49]   The protection of selenium against cadmium-induced mitophagy via modulating nuclear xenobiotic receptors response and oxidative stress in the liver of rabbits [J].
Zhang, Linwei ;
Yang, Fan ;
Li, Yong ;
Cao, Huabin ;
Huang, Aimin ;
Zhuang, Yu ;
Zhang, Caiying ;
Hu, Guoliang ;
Mao, Yaqing ;
Luo, Junrong ;
Xing, Chenghong .
ENVIRONMENTAL POLLUTION, 2021, 285
[50]   Protective effects of selenium yeast against cadmium-induced necroptosis via inhibition of oxidative stress and MAPK pathway in chicken liver [J].
Wang, Yong ;
Chen, Hongwei ;
Chang, Weihua ;
Chen, Rong ;
Xu, Shiwen ;
Tao, Dayong .
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2020, 206