Korean J Physiol Pharmacol.  2020 Jul;24(4):311-317. 10.4196/kjpp.2020.24.4.311.

Exploring the beneficial role of telmisartan in sepsis-induced myocardial injury through inhibition of high-mobility group box 1 and glycogen synthase kinase-3β/nuclear factor-κB pathway

• Jin Y
• Wang H
• Li J
• Dang M
• Zhang W
• Lei Y
• Zhao H

• KMID: 2503324
• DOI: http://doi.org/10.4196/kjpp.2020.24.4.311

Abstract

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

Keyword

High-mobility group protein; HMGB1; Kinases; Sepsis; Telmisartan

Figure

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  Fig. 1 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on creative kinase-MB (CK-MB) levels in the blood. Values are expressed as mean ± standard deviation with n = 8. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

• 

  Fig. 2 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on cardiac troponin I (cTnI) levels in the blood. Values are expressed as mean ± standard deviation with n = 8. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

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  Fig. 3 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on interleukin (IL)-6 levels in the blood. Values are expressed as mean ± standard deviation with n = 8. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

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  Fig. 4 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on p-GSK-3β/GSK-3β ratio in the myocardial tissue. Values are expressed as mean ± standard deviation with n = 8. GSK-3β, glycogen synthase kinase-3β. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

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  Fig. 5 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on high-mobility group box 1 (HMGB1) protein expression in the myocardial tissue. Values are expressed as mean ± standard deviation with n = 8. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

• 

  Fig. 6 Effects of cecal ligation and puncture-induced sepsis and pharmacological agents on interleukin (IL)-10 levels in the blood. Values are expressed as mean ± standard deviation with n = 8. ap < 0.05 as compared to normal control; bp < 0.05 as compared to sepsis control.

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