Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

Abstract

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.

Understanding the Activation of Platelets in Diabetes and Its Modulation by Allyl Methyl Sulfide, an Active Metabolite of Garlic

“…Allyl methyl sulfide (AMS) is one of the important sulfur compounds obtained from garlic, and studies showed that AMS is a major metabolite that is detected in the human breath and plasma [ 28 ]. Our previous study on AMS suggested that chronic administration of AMS is safe in control rats, where the body weight, food, and water intake along with the histopathology of major organs and serum biomarkers remained normal [ 30 ]. Further, the same study showed a beneficial effect of AMS on isoproterenol-induced cardiac fibrosis and dysregulated extracellular matrix (ECM) deposition in the myocardium [ 30 ].…”

“…Our previous study on AMS suggested that chronic administration of AMS is safe in control rats, where the body weight, food, and water intake along with the histopathology of major organs and serum biomarkers remained normal [ 30 ]. Further, the same study showed a beneficial effect of AMS on isoproterenol-induced cardiac fibrosis and dysregulated extracellular matrix (ECM) deposition in the myocardium [ 30 ]. Also, our recent finding showed a cardioprotective effect of AMS in pressure overload-induced cardiac hypertrophy and heart failure by ameliorating endogenous antioxidants and mitochondrial function [ 31 ].…”

“…Every week, the body weight of all animals was recorded to understand the body weight gain or loss during the experimental period and glucose levels were monitored by using a glucometer (Accu Chek Active, Roche). The doses of AMS and aspirin were chosen from our previous work and scientific literature [ 30 , 31 ].…”

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

“…A recent study further shows that treatment with SG1002 can prevent Hcy-induced hypertrophy in CBS +/- mice and improve cardiac function by reducing MMP activity and TGF-β activation [ 164 ]. Another H 2 S-releasing compound, allyl methyl sulfide, has been shown to attenuate isoproterenol-induced CH in rats by restoring the levels of MMP-2 and -9 as well as diminishing ROS and apoptosis activities [ 165 ]. In addition, a previous study showed that NaHS treatment can efficiently reduce the oxidative stress, apoptosis, and cardiac dysfunction in isoproterenol-induced CH by decreasing the expression of NOX4, caspase-3, and cytochrome c, which are the key players in the cardiac mitochondrial pathway [ 166 ].…”

Peroxiredoxin-5 Knockdown Accelerates Pressure Overload-Induced Cardiac Hypertrophy in Mice

“…Pathological cardiac hypertrophy is a common pathophysiological process of various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure [ 1 – 3 ]. It presents as thickening of the ventricular wall and decreased compliance of the ventricular wall [ 4 – 6 ].…”