title: Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats.
abstract: Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Yao-Te
authors.initials: YT
authors.lastname: Huang
authors.forename: Chun-Hsu
authors.initials: CH
authors.lastname: Yao
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Way
authors.forename: Kung-Wei
authors.initials: KW
authors.lastname: Lee
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Tsai
authors.forename: Hsiu-Chung
authors.initials: HC
authors.lastname: Ou
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004220:Disulfides / Q000494:pharmacology*; D005737:Garlic; D006321:Heart / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D013440:Sulfides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D053218:Receptors, Death Domain; D013440:Sulfides; C042577:diallyl trisulfide; C002744:3-nitrotyrosine; D014443:Tyrosine; C028009:diallyl disulfide; C038491:allyl sulfide; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D053148:Caspase 3