s-allylcysteine and Myocardial-Infarction

S‑allyl‑cysteine sulfoxide (alliin) is the main organosulfur component of garlic and its preparations. The present study aimed to examine the protective effect of alliin on cardiac function and the underlying mechanism in a mouse model of myocardial infarction (MI). Notably, alliin treatment preserved heart function, attenuated the area of infarction in the myocardium of mice and reduced lesions in the myocardium, including cardiomyocyte fibrosis and death. Further mechanistic experiments revealed that alliin inhibited necroptosis but promoted autophagy in vitro and in vivo. Cell viability assays showed that alliin dose‑dependently reduced the necroptotic index and inhibited the expression of necroptosis‑related receptor‑interacting protein 1, receptor‑interacting protein 3 and tumor necrosis factor receptor‑associated factor 2, whereas the levels of Beclin 1 and microtubule‑associated protein 1 light chain 3, which are associated with autophagy, exhibited an opposite trend upon treatment with alliin. In addition, the level of peroxisome proliferator‑activated receptor γ was increased by alliin. Collectively, these findings demonstrate that alliin has the potential to protect cardiomyocytes from necroptosis following MI and that this protective effect occurs via the enhancement of autophagy.

Topics: Animals; Apoptosis; Autophagy; Cell Survival; Cysteine; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Necroptosis; Receptor-Interacting Protein Serine-Threonine Kinases; Safrole; Signal Transduction

This study was aimed to evaluate the preventive role of S-allylcysteine (SAC) on creatine kinase-MB, iron, iron binding capacity, uric acid, total protein, membrane-bound enzymes such as sodium potassium-dependent adenosine triphosphatase, calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol-induced myocardial infarction in rats. Male albino Wistar rats were pre-treated with SAC (50, 100 and 150 mg/kg) daily for a period of 45 days. After the treatment period, isoproterenol (150 mg/kg) was subcutaneously injected in rats at an interval of 24 hr for 2 days. Isoproterenol-induced rats showed significantly (P < 0.05) increased activities of serum creatine kinase-MB and calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase in the heart, and the levels of iron and uric acid in serum and significantly (P < 0.05) decreased the levels of plasma iron binding capacity, plasma total protein, plasma albumin/globulin ratio and activity of sodium potassium-dependent adenosine triphosphatase in the heart. Isoproterenol induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pre-treatment with SAC (100 and 150 mg/kg) daily for a period of 45 days exhibited significant (P < 0.05) effect and altered these biochemical parameters positively. SAC (50, 100 and 150 mg/kg) treatment to normal rats did not exhibit any significant effect in any of the parameters studied. Thus, our study shows that SAC has a protective role in isoproterenol-induced myocardial infarction in rats. The observed effects might be due to the free radical scavenging, antioxidant and membrane stabilizing properties of SAC.

Topics: Adenosine Triphosphatases; alpha-Tocopherol; Animals; Antioxidants; Blood Proteins; Cell Membrane; Creatine Kinase, MB Form; Cysteine; Glycoproteins; Iron; Iron-Binding Proteins; Isoproterenol; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Uric Acid

This study was aimed to evaluate the preventive role of S-allylcysteine (SAC) on mitochondrial and lysosomal enzymes in isoproterenol (ISO)-induced rats. Male albino Wistar rats were pretreated with SAC (50, 100 and 150 mg/kg) daily for a period of 45 days. After the treatment period, ISO (150 mg/kg) was subcutaneously injected to rats at an interval of 24 h for two days. The activities of heart mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome C oxidase) were decreased significantly (p<0.05) in ISO-induced rats. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-D and acid phosphatase) were increased significantly (p<0.05) in serum and heart of ISO-induced rats. Pretreatment with SAC (100 mg/kg and 150 mg/kg) for a period of 45 days increased significantly (p<0.05) the activities of mitochondrial and respiratory chain enzymes and decreased the activities of lysosomal enzymes significantly (p<0.05) in ISO-induced rats. Oral administration of SAC (50, 100 and 150 mg/kg) for a period of 45 days to normal rats did not show any significant (p<0.05) effect in all the parameters studied. The altered electrocardiogram (ECG) of ISO-treated rats was also restored to near normal by treatment with SAC (100 and 150 mg/kg). These results confirm the efficacy of SAC in alleviating ISO-induced cardiac damage.

Topics: Adrenergic beta-Agonists; alpha-Tocopherol; Animals; Antineoplastic Agents; Cysteine; Electrocardiography; Heart Diseases; Isoproterenol; Lysosomes; Male; Mitochondria, Heart; Myocardial Infarction; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances

S-allylcysteine (SAC) is an organosulfur-containing compound derived from garlic. Studies have shown that garlic is beneficial in the treatment of cardiovascular diseases. This study aims to elucidate if SAC is responsible for this cardioprotection using acute myocardial infarction (AMI) rat models. In addition, we hypothesized that SAC may mediate cardioprotection via a hydrogen sulfide (H(2)S)-related pathway. Rats were pretreated with saline, SAC (50 mg x kg(-1) x day(-1)), SAC + propagylglycine (PAG; 50 mg + 10 mg x kg(-1) x day(-1)) or PAG (10 mg x kg(-1) x day(-1)) for 7 days before AMI induction and killed 48 h after. Our results showed that SAC significantly lowered mortality (12.5% vs. 33.3%, P < 0.05) and reduced infarct size. SAC + PAG- and PAG-treated rats had larger infarct sizes than controls (60.9 +/- 0.01 and 62.0 +/- 0.03%, respectively, vs. 50.0 +/- 0.03%; P < 0.05). Pretreatment with SAC did not affect BP, but BP was significantly elevated in SAC + PAG and PAG-treated groups (P < 0.05). In addition, plasma H(2)S levels and left ventricular cystathionine-gamma-lyase (CSE) activities were analyzed to investigate the involvement of H(2)S. CSE is the enzyme responsible for H(2)S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75 +/- 0.34 vs. 1.23 +/- 0.16 micromol x g protein(-1) x h(-1); P < 0.01). SAC + PAG-treated rats had significantly lower CSE activity compared with the SAC-treated group (1.22 +/- 0.27 vs. 2.75 +/- 0.34 micromol x g protein(-1) x h(-1); P < 0.05). Similarly, SAC-treated rats had higher plasma H(2)S concentration compared with controls and the SAC + PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1-fold of control; P < 0.05), whereas SAC + PAG and PAG downregulated its expression (0.88-fold of control in both groups; P < 0.005). In conclusion, our study provides novel evidence that SAC is protective in myocardial infarction via an H(2)S-related pathway.

Topics: Animals; Cardiotonic Agents; Cystathionine gamma-Lyase; Cysteine; Garlic; Humans; Hydrogen Sulfide; Male; Myocardial Infarction; Plant Extracts; Rats; Rats, Wistar; Signal Transduction

Topics: Animals; Cardiotonic Agents; Cysteine; Garlic; Humans; Hydrogen Sulfide; Myocardial Infarction; Plant Extracts; Rats; Signal Transduction