temocapril-hydrochloride and Myocarditis

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.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Newborn; Antioxidants; Autoimmune Diseases; Blotting, Western; Cells, Cultured; Dose-Response Relationship, Drug; Immunohistochemistry; Myocarditis; Myocytes, Cardiac; Oxidation-Reduction; Oxygen; Rats; Superoxide Dismutase; Swine; Thiazepines; Thioredoxins; Time Factors; Up-Regulation

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.. The up-regulation of TRX by temocapril treatment was checked by Western blot in normal rat myocytes in vitro and in vivo, as well as in rats with experimental autoimmune myocarditis (EAM).. 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 up-regulated by the preconditioning treatment. In rats with EAM, the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg x kg(-1) x d(-1), orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. If the characteristics of this model that myocardial inflammation begins around day 15 and keeps on until day 21 is considered, temocapril treatment for 3 weeks might be thought as a preconditioning treatment.. TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Newborn; Autoimmune Diseases; Cells, Cultured; Myocarditis; Myocytes, Cardiac; Oxidation-Reduction; Rats; Rats, Inbred Lew; Superoxide Dismutase; Thiazepines; Thioredoxins; Up-Regulation

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.. In normal rat myocytes in vitro and in vivo, Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but that neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. Considering the characteristics of this model that myocardial inflammation begins around day 15 and increases until day 21, temocapril treatment for 3 weeks might be thought of as a preconditioning treatment.. 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 up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Autoimmune Diseases; Cell Culture Techniques; DNA-Binding Proteins; Drosophila Proteins; Membrane Proteins; Myocarditis; Oxidation-Reduction; Rats; Rats, Inbred Lew; Superoxide Dismutase; Thiazepines; Thioredoxins; Transcription Factors; Up-Regulation