Interleukin-6 expression and its modulation by diacerein in a rat model of chronic stress induced cardiac dysfunction

被引:18
作者
Agarwal, Vipul [1 ]
Kaushik, Arjun Singh [1 ]
Rehman, Mujeeba [1 ]
Chaudhary, Rishabh [1 ]
Jawaid, Talha [2 ]
Kamal, Mehnaz [3 ]
Mishra, Vikas [1 ]
机构
[1] Babasaheb Bhimrao Ambedkar Univ, Dept Pharmaceut Sci, Raebareli Rd, Lucknow 226025, Uttar Pradesh, India
[2] Imam Mohammad Ibn Saud Islam Univ IMSIU, Dept Pharmacol, Coll Med, Riyadh 13317, Saudi Arabia
[3] Prince Sattam Bin Abdulaziz Univ, Dept Pharmaceut Chem, Coll Pharm, POB 173, Al Kharj 11942, Saudi Arabia
关键词
Chronic unpredictable stress; Interleukin-6; Pro-inflammatory cytokines; Cardiac dysfunction; Diacerein; HEART-RATE-VARIABILITY; CYTOKINES; DISEASE; RISK; IL-6; INFLAMMATION; RECRUITMENT; FAILURE; PROTEIN;
D O I
10.1016/j.heliyon.2021.e08522
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
People with chronic stress have higher levels of pro-inflammatory cytokines, which enhance their susceptibility to cardiovascular diseases. Diacerein has ability to modulate pro-inflammatory cytokines such as IL-18 and IL-6; however, its efficacy in chronic stress associated cardiovascular diseases is not yet assessed. In this study, we standardized a rat model of chronic unpredictable stress (CUS) demonstrating cardiovascular dysfunctions and further assessed the effect of IL-6 modulator, diacerein, on cardiovascular functions in CUS exposed rats. The CUS procedure consisted of exposing male albino Wistar rats to random stressors, everyday for 8 weeks. The binding affinity of diacerein with IL-6 was ascertained using Docking tools viz AutoDock and SwissDock. Moreover, diacerein was administered (50 mg/kg/day x 20 days P.O) post CUS exposure to rats and the serum IL-6 levels and heart functions of CUS rats were determined by ELISA and ECG-HRV analysis, respectively. 8 weeks of CUS exposure resulted in two-fold increase in serum corticosterone and IL-6 levels in rats. The ECG and HRV analysis of CUS rats showed altered sinus rhythm, elevated heart rate, systolic blood pressure and sympathetic tone. Molecular docking studies revealed diacerein high binding affinity towards IL-6 receptor. The post-treatment of diacerein in CUS rats prevented these cardiovascular dysfunctions. Our findings thus suggests that IL-6 may have a prominent role in chronic stress induced cardiovascular dysfunctions and diacerein, could be used as a preventive measure for such conditions.
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页数:11
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