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

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.

Clinical Features of Graves' Ophthalmopathy and Impact of Enalapril on the Course of Mild Graves’ Ophthalmopathy: A Pilot Study

Background: Inflammation, oxidative stress, and adipogenesis are associated with Graves’ ophthalmopathy (GO) progression. Objective: We conducted a pilot study to investigate the effect of Enalapril on patients with mild ophthalmopathy. Method: Based on the comprehensive eye examination, 12 patients with mild ophthalmopathy were selected from referred Graves’ patients and treated with Enalapril (5 mg daily) for 6 months. Clinical and ophthalmological examination [IOP (Intraocular Pressure), vision, Margin reflex distance and exophthalmia measurement, CAS (clinical activity score) and VISA [V (vision); I (inflammation/ congestion); S (strabismus/motility restriction); and A (appearance/exposure] score assessment) was performed at the beginning, 3 months and 6 months of the study period. Quality of life was also evaluated using a standard questionnaire. Results: Mean exophthalmia at the first visit was 18.75 ± 2.39, 3 months later 18.53 ± 2.39 and 6 months later was 17.92 ± 2.31, respectively. Mean CAS was 0.71 ± 0.82 (first visit), 0.57 ± 0.54 (3 months) and 0.14 ± 0.36 (6 months), respectively. Mean Margin reflex distance was 9.09 ± 4.36 (first visit) and 9.60 ± 4.40 (6 months), respectively. There were significant differences in the case of exophthalmia (P=0.002), CAS (P=0.006), and Margin reflex distance (P=0.029) between the first visit and 6 months after treatment. The difference between the score of quality of life in patients with GO after 6 months of follow up was statistically significant (P = 0.006). Conclusion: Our results showed that Enalapril treatment could ameliorate the clinical course of GO according to the ophthalmologic examinations and subjective parameters of disease progression. However, further studies should be performed to determine the efficacy of Enalapril in Graves’ ophthalmopathy treatment.