Carnosic acid attenuates doxorubicin-induced cardiotoxicity by decreasing oxidative stress and its concomitant pathological consequences

被引：17

作者：

Manna, Prasenjit ^{[1
,2
]}

Dewanjee, Saikat ^{[3
]}

Joardar, Swarnalata ^{[3
]}

Chakraborty, Pratik ^{[3
]}

Bhattacharya, Hiranmoy ^{[3
]}

Bhanja, Shrestha ^{[3
]}

Bhattacharyya, Chiranjib ^{[3
]}

Bhowmik, Manas ^{[4
]}

Bhowmick, Shovonlal ^{[5
]}

Saha, Achintya ^{[5
]}

Das, Joydeep ^{[6
]}

Sil, Parames C. ^{[7
]}

机构：

[1] CSIR, Ctr Infect Dis, North East Inst Sci & Technol, Jorhat 785006, Assam, India

[2] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India

[3] Jadavpur Univ, Dept Pharmaceut Technol, Adv Pharmacognosy Res Lab, Kolkata 700032, India

[4] Jadavpur Univ, Dept Pharmaceut Technol, Adv Pharmaceut Res Lab, Kolkata 700032, India

[5] Univ Calcutta, Dept Chem Technol, Kolkata 700009, India

[6] Mizoram Univ, Dept Chem, Phys Sci, Aizawl 796004, Mizoram, India

[7] Bose Inst, Div Mol Med, P-1-12,CIT Scheme 7 M, Kolkata 700054, India

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2022年 / 166卷

关键词：

Antioxidant; Apoptosis; Cardiotoxicity; Carnosic acid; Doxorubicin; Oxidative stress; ARJUNOLIC ACID; APOPTOSIS; INFLAMMATION; IMPAIRMENT; ACTIVATION; PATHWAY; INJURY; TISSUE;

D O I：

10.1016/j.fct.2022.113205

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

This work aimed to reveal the protective mechanism of CA against Dox (doxorubicin)-induced cardiotoxicity. In isolated murine cardiomyocytes, CA showed a concentration-dependent cytoprotective effect against Dox. Dox treatment significantly (p < 0.01) increased the formation of reactive oxygen species (ROS), increased NO levels, activated NADPH oxidase, and inactivated the cellular redox defense mechanism in cardiac cells, resulting in augmented oxidative stress in cardiomyocytes and rat hearts. Dox-induced oxidative stress significantly (p < 0.01) upregulated several pathogenic signal transductions, which induced apoptosis, inflammation, and fibrosis in cardiomyocytes and murine hearts. In contrast, CA significantly (p < 0.05-0.01) reciprocated Dox-induced cardiac apoptosis, inflammation, and fibrosis by suppressing oxidative stress and interfering with pathological signaling events in both isolated murine cardiomyocytes and rat hearts. CA treatment significantly (p < 0.05-0.01) countered Dox-mediated pathological changes in blood parameters in rats. Histological examinations backed up the pharmacological findings. In silica chemometric investigations predicted potential interactions between CA and studied signal proteins, as well as the drug-like features of CA. Thus, it would be concluded that CA has the potential to be regarded as an effective agent to alleviate Dox-mediated cardiotoxicity in the future.

引用

页数：15