PMID- 32445760 OWN - NLM STAT- MEDLINE DCOM- 20200625 LR - 20211204 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 255 DP - 2020 Aug 15 TI - Sulforaphane protects against skeletal muscle dysfunction in spontaneous type 2 diabetic db/db mice. PG - 117823 LID - S0024-3205(20)30572-5 [pii] LID - 10.1016/j.lfs.2020.117823 [doi] AB - AIMS: Skeletal muscle diseases have become to be the most common complication in patients with type 2 diabetic mellitus (T2DM). However, the effective therapies against skeletal muscle diseases are not yet available. Sulforaphane (SFN) is an organic isothiocyanate found in cruciferous plants. Our aim was to explore whether SFN could attenuate the skeletal muscle diseases in spontaneous type 2 diabetic db/db mice. MATERIALS AND METHODS: The db/m and littermate db/db mice were treated with SFN or dimethyl sulfoxide. The grip strength of mice was measured by a grasping forcing machine. The electron transmission microscopy was used to perform the skeletal muscle. The western blot was used to detect the nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signal pathway related proteins, and inflammatory and apoptotic associated proteins. The mRNA levels of anti-inflammatory and anti-oxidative relative genes were detected by RT-QPCR. KEY FINDINGS: We found that SFN could significantly increase the grip strength of the db/db mice. The lean mass and gastrocnemius mass were increased in the db/db mice after administration with SFN. Additionally, the db/db mice restored the skeletal muscle fiber organization after SFN treatment. Mechanistically, SFN could activate the Nrf2/HO-1 signal pathway, and downregulate the expression of inflammatory and apoptotic associated proteins. Furthermore, SFN could also regulate the mRNA levels of anti-inflammatory and anti-oxidative related genes. SIGNIFICANCE: Our results demonstrated that SFN can protect against skeletal muscle diseases in db/db type 2 diabetic mice and provide a potential drug to prevent skeletal muscle dysfunction in T2DM patients. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Wang, Meili AU - Wang M AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Pu, Die AU - Pu D AD - Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Zhao, Yuxing AU - Zhao Y AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Chen, Jinliang AU - Chen J AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Zhu, Shiyu AU - Zhu S AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Lu, Ankang AU - Lu A AD - Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Liao, Zhilin AU - Liao Z AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Sun, Yue AU - Sun Y AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Xiao, Qian AU - Xiao Q AD - Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: xiaoqian1956@126.com. LA - eng PT - Journal Article DEP - 20200520 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Antioxidants) RN - 0 (Isothiocyanates) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - 0 (RNA, Messenger) RN - 0 (Sulfoxides) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - GA49J4310U (sulforaphane) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Diabetes Mellitus, Experimental/*complications/drug therapy MH - Diabetes Mellitus, Type 2/*complications/drug therapy MH - Heme Oxygenase-1/metabolism MH - Isothiocyanates/*pharmacology MH - Male MH - Membrane Proteins/metabolism MH - Mice MH - Muscle, Skeletal/*drug effects/pathology MH - Muscular Diseases/etiology/*prevention & control MH - NF-E2-Related Factor 2/metabolism MH - RNA, Messenger/metabolism MH - Sulfoxides OTO - NOTNLM OT - Nrf2/HO-1 signal pathway OT - Skeletal muscle OT - Sulforaphane COIS- Declaration of competing interest All the authors declare that there are no conflicts of interest. EDAT- 2020/05/24 06:00 MHDA- 2020/06/26 06:00 CRDT- 2020/05/24 06:00 PHST- 2020/01/11 00:00 [received] PHST- 2020/05/08 00:00 [revised] PHST- 2020/05/18 00:00 [accepted] PHST- 2020/05/24 06:00 [pubmed] PHST- 2020/06/26 06:00 [medline] PHST- 2020/05/24 06:00 [entrez] AID - S0024-3205(20)30572-5 [pii] AID - 10.1016/j.lfs.2020.117823 [doi] PST - ppublish SO - Life Sci. 2020 Aug 15;255:117823. doi: 10.1016/j.lfs.2020.117823. Epub 2020 May 20.