S-Allylcysteine limits cardiac structural changes via antioxidant status in ovariectomized rats with induced myocardial injury

Abstract

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Higher Education, Malaysia (Fundamental Research Grant Scheme) Background Cardiovascular disease is the primary cause of death in Malaysia. Past studies have shown the incidence of cardiovascular diseases among post-menopausal women increased where their estrogen level is deficient. Thus, there is growing interest in investigating alternative approach in which to limit cardiovascular injury for post-menopausal women. S-Allylcysteine (SAC) is one of the aged garlic extract compounds that has shown its cardioprotective effect through mitochondrial preservation and CSE/hydrogen sulfide pathway. Purpose Hence, this study was aimed to investigate the effect of SAC in ovariectomized rats with isoprenaline-induced myocardial injury. Methods Ovariectomy surgery (ovary removal) was done onto 32 female Wistar rats, whereas eight rats had the same surgery without ovary removal (Sham). After three weeks of recovery, all rats received subcutaneous administration of either normal saline (Sham, OVX) or isoprenaline 85 mg/kg (OVXIM, 2x) to induce myocardial injury. Then, oral gavage of either distilled water (Sham, OVX, OVXIM) or SAC 100 mg/kg (OVXS, OVXIMS) were given to the rats for one week. Finally, the rats were anesthetized before the hearts were cannulated on Langendorff isolated heart system for cardiac function measurement. Results The rat models were validated by decreased estrogen level, while cardiac injury was from the increased ST elevation on electrocardiogram and plasma Troponin T level. Systolic blood pressure in OVXS (142.45±5.17 mmHg vs 120.53±6.75 mmHg) showed significant decrease after receiving SAC. Although SAC did not reduce oxidative stress product TBARS in OVXIM, but it increased GSH (OVX: 0.0291±0.002 vs. OVXMIS: 0.0644±0.005 nmol/mg protein) and SOD (OVX: 0.7148±0.039 vs OVXMIS: 0.4991±0.068 E/mg protein/min) antioxidants in the treatment group. This is probably due to the allyl and cysteine group in the SAC molecule that has antioxidative property which protects vascular tissue, thus contributes to the lowering of blood pressure. Histological observation showed that SAC treatment was able to limit hypertrophy and collagen deposition in OVXIM group. This suggests that SAC antioxidant action may be able to limit the cell injury from oxidative stress, thus decreasing fibrosis effect (OVXIM: 5.41 ± 1.15 vs. OVXIMS: 2.31 ± 0.42%) and preserving cardiomyocyte size (OVXIM: 5.41 ± 1.15 vs. OVXIMS: 2.31 ± 0.42 µm2). Despite the histological alteration, the Langendorff-perfused hearts of the treated rats showed similar function as Sham. CSE enzyme activity and protein expression in OVXS tended to return to the same level as Sham. Conclusion In summary, this study showed SAC’s potential in preserving cardiac structure in estrogen-deficient condition, but in-depth study is warranted to further understand antioxidant and CSE enzyme signalling pathway.

Bioactive Compounds and Cardiac Fibrosis: Current Insight and Future Prospect

“…S-allylcysteine: An organosulfur compound found in garlic, it can inhibit the proliferation of cardiac fibroblasts and reduce collagen deposition in the heart, which may help prevent cardiac fibrosis [148]. A study by Zainalabidin et al also showed that S-allylcysteine reduces adverse cardiac remodeling after myocardial infarction in a rat model and also limits cardiac fibrosis in rats [149].…”