PMID- 32138157 OWN - NLM STAT- MEDLINE DCOM- 20210308 LR - 20210308 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 3 DP - 2020 Mar 3 TI - 3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice. LID - 10.3390/cells9030597 [doi] LID - 597 AB - Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotusobliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction. FAU - Giridharan, Vijayasree V AU - Giridharan VV AD - Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. AD - Faculty of Applied Life Sciences, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences Niigata, Niigata 956-8603, Japan. FAU - Karupppagounder, Vengadeshprabhu AU - Karupppagounder V AD - Department of Orthopedics and Rehabilitation, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA. AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha ku, Niigata 956-8603, Japan. FAU - Arumugam, Somasundaram AU - Arumugam S AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha ku, Niigata 956-8603, Japan. AD - National Institute of Pharmaceutical Education and Research (NIPER), Jadavpur, Kolkata, West Bengal 700032, India. FAU - Nakamura, Yutaka AU - Nakamura Y AD - Faculty of Applied Life Sciences, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences Niigata, Niigata 956-8603, Japan. FAU - Guha, Ashrith AU - Guha A AD - Department of Cardiology, Houston Methodist Hospital, Houston, TX 77030, USA. FAU - Barichello, Tatiana AU - Barichello T AD - Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. AD - Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. AD - Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth, Graduate School of Biomedical Sciences, Houston, TX 77030, USA. FAU - Quevedo, Joao AU - Quevedo J AD - Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. AD - Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA. AD - Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth, Graduate School of Biomedical Sciences, Houston, TX 77030, USA. AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma 88800-000, SC, Brazil. FAU - Watanabe, Kenichi AU - Watanabe K AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha ku, Niigata 956-8603, Japan. AD - Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Niigata University Graduate School of Medical and Dental Sciences, 757, Ichibancho, Asahimachidori, Chuo ku, Niigata City 951-8510, Japan. FAU - Konishi, Tetsuya AU - Konishi T AD - Niigata University of Pharmacy & Applied Life Sciences (NUPALS), LIAISON R/D Center, Niigata 956-8603, Japan. FAU - Thandavarayan, Rajarajan A AU - Thandavarayan RA AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha ku, Niigata 956-8603, Japan. AD - Department of Cardiology, Houston Methodist Hospital, Houston, TX 77030, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200303 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (3,4-dihydroxybenzalacetone) RN - 0 (Caffeic Acids) SB - IM MH - Aged MH - Aging/*drug effects MH - Animals MH - Apoptosis MH - Caffeic Acids/pharmacology/*therapeutic use MH - DNA Damage/*genetics MH - Fibrosis MH - Gene Expression/*genetics MH - Humans MH - Male MH - Mice MH - Myocardium/*pathology PMC - PMC7140466 OTO - NOTNLM OT - 3,4-dihydroxybenzalacetone OT - DNA damage OT - SAMP8 OT - apoptosis OT - fibrosis COIS- The authors declare no conflicts of interest. EDAT- 2020/03/07 06:00 MHDA- 2021/03/09 06:00 PMCR- 2020/03/01 CRDT- 2020/03/07 06:00 PHST- 2020/02/06 00:00 [received] PHST- 2020/02/27 00:00 [revised] PHST- 2020/02/27 00:00 [accepted] PHST- 2020/03/07 06:00 [entrez] PHST- 2020/03/07 06:00 [pubmed] PHST- 2021/03/09 06:00 [medline] PHST- 2020/03/01 00:00 [pmc-release] AID - cells9030597 [pii] AID - cells-09-00597 [pii] AID - 10.3390/cells9030597 [doi] PST - epublish SO - Cells. 2020 Mar 3;9(3):597. doi: 10.3390/cells9030597.