tranilast and Heart-Diseases

An increase in oxidative stress is an important pathological mechanism of heart injury induced by doxorubicin (DOX). Tranilast is an anti-allergy drug that has been shown to possess good antioxidant activity in previous studies. The overexpression and secretion of chymase by mast cells (MCs) increase the pathological overexpression of angiotensin II (Ang II), which plays a crucial role in myocardial hypertrophy and the deterioration of heart disease. The MC stabilizer tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid; tran) prevents mast cells from degranulating, which may reduce DOX-induced Ang II synthesis. Therefore, in the present study, we hypothesized that tranilast will protect rats from DOX-induced myocardial damage via its antioxidant activity, thereby inhibiting Ang II expression. Thirty male Wistar rats were divided into three groups (n = 10 in each group) that received DOX, a combination of DOX and tranilast or saline (the control group) to test this hypothesis. Tranilast suppressed chymase expression, reduced Ang II levels and prevented the myocardial hypertrophy and the deterioration of heart function induced by DOX. Based on the findings of the present study, the suppression of chymase-dependent Ang-II production and the direct effect of tranilast on the inhibition of apoptosis and fibrosis because of its antioxidant stress capacity may contribute to the protective effect of tranilast against DOX-induced myocardial hypertrophy.

Topics: Angiotensin II; Animals; Antioxidants; Cardiomegaly; Doxorubicin; Fibrosis; Heart Diseases; Male; Mast Cells; Myocardium; ortho-Aminobenzoates; Oxidative Stress; Rats; Rats, Wistar

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Clinical Trials as Topic; Coronary Artery Bypass; Coronary Restenosis; Heart Diseases; Heart Failure; Humans; ortho-Aminobenzoates; Propafenone

Angiotensin II recruits transforming growth factor beta(1) (TGFbeta(1)) and is related to left ventricular fibrosis. However, it is unclear whether chronic in vivo reduction in left ventricular TGFbeta(1) expression blunts fibrosis and improves outcome in angiotensin II-dependent hypertension. Four-week-old male hypertensive TGR(mRen2)27 (Ren2) rats received either normal food, low-dose losartan (0.5 mg. kg(-1). d(-1)), or tranilast (a nonspecific TGFbeta inhibitor; 400 mg. kg(-1). d(-1)) (n=10 for each group) for 12 weeks and were compared with Sprague-Dawley control rats. The effect of tranilast on survival was evaluated in 34 additional untreated homozygous Ren2 rats. Tranilast or low-dose losartan did not lower blood pressure. However, the increase in left ventricular weight (Ren2 versus SD 3.1+/-0.16 versus 2.1+/- 0.06 mg/g body wt; P<0.05) was significantly (P<0.05) blunted by both tranilast (2.7+/-0.05) and losartan (2.7+/-0.07). Both drugs prevented the increase in left ventricular TGFbeta(1) mRNA and fibronectin mRNA and blunted the increase in hydroxyproline content and the increase in perivascular fibrosis. The perivascular fibrosis score correlated significantly with the level of expression of TGFbeta(1) (r=0.62; P=0.019). In situ hybridization demonstrated increases in TGFbeta(1) mRNA, predominantly in perivascular and nonmyocyte areas. Both drugs did not prevent the decrease in systolic or diastolic dP/dt, but tranilast significantly improved the survival of untreated Ren2 rats (P=0.029). In conclusion, TGFbeta(1) mRNA expression is increased predominantly in nonmyocyte regions in the hypertrophied left ventricle in this angiotensin II-dependent model of hypertension. This increase is probably due to high angiotensin II levels rather than to hypertension. This is the first study to suggest that chronic inhibition of TGFbeta(1) expression attenuates left ventricular hypertrophy and fibrosis, even without lowering blood pressure.

Topics: Animals; Cardiomegaly; Disease Models, Animal; Fibrosis; Heart Diseases; Heart Ventricles; Hypertension; Losartan; Male; ortho-Aminobenzoates; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Receptors, Transforming Growth Factor beta; RNA, Messenger; Survival Analysis; Transforming Growth Factors; Ventricular Function

A case of tranilast (Rizaben)-induced cystitis accompanied with possibly hypereosinophilic heart syndrome was described. A 75-year-old male, who had been taking tranilast for allergic dermatitis for two months, was admitted for severe bladder stimulating symptoms which was unresponsive to antibiotic therapies. Clinical examination revealed tenderness of the prostate, aseptic pyuria, eosinophilia, liver dysfunction and electrocardiographic disorders including atrial fibrillation, T-wave inversions and lowered ST segment without any cardiac symptoms. Cystitis symptoms, pyuria, eosinophilia and liver dysfunction improved within several days after discontinuance of tranilast, and ST-T changes on ECG gradually normalized within a few months. Tranilast-induced cystitis has been demonstrated as a type of eosinophilic cystitis. Since pathologic findings of eosinophilic cystitis and hypereosinophilic heart syndrome are markedly similar and all symptoms and signs disappeared after deprivation of tranilast, it appears likely that eosinophilic inflammation was induced to the heart, liver, bladder and prostate of the current patient by tranilast.

Topics: Aged; Cystitis; Dermatitis, Allergic Contact; Electrocardiography; Eosinophilia; Heart; Heart Diseases; Histamine H1 Antagonists; Humans; Male; ortho-Aminobenzoates