title: Isothiocyanates ameliorate the symptom of heart dysfunction and mortality in a murine AIDS model by inhibiting apoptosis in the left ventricle.
abstract: Cardiac involvement has been reported in as many as 45-55% of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), and significant cardiac morbidity is reported in 6-7% of HIV patients. We investigated the inhibitory effects of isothiocyanates (ITCs) on heart dysfunction and mortality by regulating apoptosis in the left ventricle of the heart in a murine AIDS model. Mice were divided into six groups: an uninfected group, an untreated LP-BM5 retrovirus-infected group, and four LP-BM5 retrovirus-infected groups treated with one of four ITCs (sulforaphane [SUL], indolo[3,2-b]carbazole, benzyl isothiocyanate [BITC], or phenethyl isothiocyanate [PEITC]). After 16 weeks, the median survival time of the LP-BM5 retrovirus-infected mice was 87 days, whereas that of the uninfected control group and all ITC treatment groups was over 112 days. SUL, PEITC, and BITC significantly inhibited apoptosis in the left ventricle by increasing the Bcl-2/Bax ratio compared with LP-BM5-infected mice. In addition, SUL and PEITC suppressed inducible nitric oxide synthase (iNOS) expression at both the mRNA and protein levels in the left ventricle of heart tissue infected with the LP-BM5 retrovirus by inactivating cytoplasmic nuclear factor κB (NF-κB). In conclusion, LP-BM5 retrovirus infection was related to survival of murine AIDS mice, and NF-κB-mediated iNOS expression may be an important mediator of left ventricle dysfunction of the heart. Furthermore, certain ITCs may have the potential to improve AIDS-related heart dysfunction due to their inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.
authors.affiliation: Research Institute of Clinical Nutrition, Department of Medical Nutrition, Kyung Hee University, Yongin, Korea.
authors.forename: Jin-Nyoung
authors.initials: JN
authors.lastname: Ho
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Park
authors.forename: Sunoh
authors.initials: S
authors.lastname: Kim
authors.forename: Woojin
authors.initials: W
authors.lastname: Jun
authors.forename: Ryowon
authors.initials: R
authors.lastname: Choue
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017879:Isothiocyanates / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013454:Sulfoxides; D016019:Survival Analysis; D013861:Thiocyanates / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000178:diet therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D002316:Cardiotonic Agents; D017879:Isothiocyanates; D016328:NF-kappa B; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; C058305:phenethyl isothiocyanate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C016766:sulforaphane