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BMC Pharmacol Toxicol. 2018 Nov 9;19(1):71. doi: 10.1186/s40360-018-0262-x.

3,3'-Diindolylmethane protects cardiomyocytes from LPS-induced inflammatory response and apoptosis.

Luo Q1,2,3, Yang A1,2,3, Cao Q1,2,3, Guan H4,5,6.

Author information

1
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
2
Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
3
Hubei Key Laboratory of Cardiology, Wuhan, Hubei, 430060, People's Republic of China.
4
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China. 2016203020014@whu.edu.cn.
5
Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, 430060, People's Republic of China. 2016203020014@whu.edu.cn.
6
Hubei Key Laboratory of Cardiology, Wuhan, Hubei, 430060, People's Republic of China. 2016203020014@whu.edu.cn.

Abstract

BACKGROUND:

3,3'-Diindolylmethane (DIM) has been extensively studied as a potential therapeutic drug with free radical scavenging, antioxidant and anti-angiogenic effects. However, whether DIM has similar effects on cardiomyocytes remains unknown. Here we evaluated DIM's influence on inflammation and apoptosis of H9C2 cardiomyocytes induced by LPS and to explore the possible mechanism of the effects.

METHODS:

H9C2 cells were incubated with DIM (10, 20 and 30 μM) with or without LPS for 24 h. The cytotoxicity of DIM was detected by CCK-8. The levels of tumour necrosis factor (TNF)-α and interleukin (IL)-6 were then measured using RT-qPCR and ELISA. Cell apoptosis rate and reactive oxygen species (ROS) content after DIM treatment were measured by flow cytometry. Expressions of NFκB, P-NFκB, IκBa, P-IκBa, Bax and Bcl-2 after DIM treatment were detected by western blot. The rate of NFκB nuclear translocation after DIM treatment was determined by immunocytochemical analysis.

RESULTS:

LPS stimulation promoted TNF-α and IL-6 mRNA expression. After treatment with various concentrations of DIM (10, 20 and 30 μM), TNF-α and IL-6 mRNA expression was clearly impaired, especially in the LPS + DIM30(μM) group. ELISA was used to measure TNF-α and IL-6 concentrations in cellular supernatant, and the result was verified to be consistent with RT-qPCR. Additionally, DIM treatment significantly blocked LPS-induced oxidative stress and inhibited LPS-induced apoptosis in H9C2 cardiomyocytes according to the results detected by flow cytometry. Moreover, compared with LPS alone, DIM significantly inhibited the LPS-induced phosphorylation of NFκB (p-NFκB) and Bax expression and increased Bcl-2 expression.

CONCLUSIONS:

DIM may have a protective effect for H9C2 cardiomyocytes against LPS-induced inflammatory response and apoptosis. DIM may be a new insight into the treatment of septic cardiomyopathy.

KEYWORDS:

DIM; H9C2; LPS; NFκB; ROS; Septic cardiomyopathy

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