Untitled

Abstract

Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was increased by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the protein carbonyl content, a marker of cellular protein oxidation, was increased accompanied with enhanced TRX expression. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. The severity of the myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21 in which TRX was up regulated when the inflammation started, but not in temocapril treatment from day 15-21 in which TRX was not up-regulated when the inflammation started. The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX increase in a preconditioning manner, although the mechanism of TRX induction by temocapril remains to be elucidated.

Antioxidant activity of the thioredoxin system

“…The TR activity in the myocardium of pigs fed with low selenium decreases (Sun et al 2020 ). The expression of Trx in myocarditis is increased, and motiflrin can reduce myocardial injury (Yuan et al 2003 ).…”

Modulation of NRF-2 Pathway Contributes to the Therapeutic Effects of Boswellia serrata Gum Resin Extract in a Model of Experimental Autoimmune Myocarditis

“…Myocarditis is characterized by cardiac inflammation, oedema, cellular infiltration, apoptosis, and necrosis of cardiomyocytes [ 1 ]. A discrepancy of reactive oxygen species (ROS) and/or an unsatisfactory cellular antioxidant defense mechanism may play a decisive role in myocardial damage in acute myocarditis [ 2 ]. Increased ROS can cause serious cardiovascular dysfunction by attacking contractile molecules or ion channels directly.…”

“…The major natural compounds present in in B. serrata extract include various classes. These are phenolic compounds, such as [2,7,8 trimethoxy-3 methyl-5,6- methylenedioxynaphtho-1,4-quinine], [diterpenoids (1S, 2E, 4S, 6E, 8R, 11S, 12R)-8, 11-Epoxy-2, 6-thunbergadiene-4, 12-diol], esters of acetic acid, such as [(E,E,10S)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadiene-1-yl] acetate, a quinoline alkaloid; benzo(h) quinolino (1″,2″:1′,2′) imidazo (4′,5′:4,5) imidazo (1,2-a) benzo-(h) quinoline, and ketones as (3E)-4- (5,5- dimethyl-1- oxaspiro [ 2 , 5 ] oct-4-yl)-3-buten-2-one] [ 11 ]. Thus, the aim of this study was to evaluate the anti-inflammatory and antioxidants effects of Boswellia serrata gum resin extract in a rat model of autoimmune myocarditis and the molecular mechanisms involved.…”