PMID- 32745770
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 160
DP  - 2020 Nov 20
TI  - Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced 
      inflammation and oxidative stress in the brain of rats.
PG  - 141-148
LID - S0891-5849(20)31154-0 [pii]
LID - 10.1016/j.freeradbiomed.2020.07.018 [doi]
AB  - Doxorubicin (DOX) is a widely used antitumor drug that causes severe 
      neurotoxicity in patients. Diallyl trisulfide (DATS) is an organosulfur compound 
      with established potent antioxidant and anti-inflammatory properties. Herein, we 
      investigated the neuroprotective efficacy of DATS in preventing DOX-induced 
      neurotoxicity in a rat model. Specifically, DATS (40 mg/kg) was administered to 
      rats 24 h after DOX treatment, once a week for 8 weeks. Our results showed that 
      DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha 
      (TNF-alpha) induced by DOX. DATS restored cerebral cortex and hippocampus 
      histopathological architecture and neuronal loss. Immunohistochemical staining 
      indicated that DATS decreased the expression of glial fibrillar acidic protein 
      (GFAP) in DOX treated rats. Components of stress-related inflammatory proteins 
      (TNF-alpha, phospho nuclear factor kappa B (NF-kappaB), inducible nitricoxide synthase 
      (iNOS) and cyclooxygenase-2 (COX-2)) were all significantly increased in the DOX 
      group, in comparison with the control group, whereas they were decreased after 
      DATS treatment. In addition, the mRNA of antioxidant enzymes (superoxide 
      dismutase 2 (SOD2), catalase, glutathione peroxidase 1, 4 (GPx1 and GPx4)) and 
      antioxidant proteins (heme oxygenase-1 (HO-1), superoxide dismutase 1, 2 (SOD1 
      and SOD2), Gamma-glutamylcysteine synthase (Gamma-GCSc)) were markedly increased in DOX 
      group compared with the control group, which were significantly attenuated by 
      DATS treatment. The upregulation of antioxidants enzymes in DOX group was 
      probably a compensatory effect against elevated oxidative stress induced by DOX. 
      DATS treatment could ameliorate this oxidative stress in brain. Our results 
      suggested that DATS has potential clinical applications in the prevention of 
      DOX-induced neurotoxicity by ameliorating inflammatory insults and oxidative 
      stress.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Leung, Wai-Shing
AU  - Leung WS
AD  - Department of Emergency Medicine, Jen-Ai Hospital, Taichung, 403, Taiwan.
FAU - Kuo, Wei-Wen
AU  - Kuo WW
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, 404, Taiwan.
FAU - Ju, Da-Tong
AU  - Ju DT
AD  - Department of Neurological Surgery, Tri-Service General Hospital, National 
      Defense Medical Center, Taipei, 114, Taiwan.
FAU - Wang, Tian-De
AU  - Wang TD
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, 404, Taiwan.
FAU - Shao-Tsu Chen, William
AU  - Shao-Tsu Chen W
AD  - Department of Psychiatry, Tzu Chi General Hospital, Hualien, 970, Taiwan; School 
      of Medicine Tzu Chi University, Hualien, 970, Taiwan.
FAU - Ho, Tsung-Jung
AU  - Ho TJ
AD  - Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, Tzu Chi University, Hualien, 970, Taiwan.
FAU - Lin, Yu Min
AU  - Lin YM
AD  - Department of Emergency Medicine, Jen-Ai Hospital, Taichung, 403, Taiwan.
FAU - Mahalakshmi, B
AU  - Mahalakshmi B
AD  - Institute of Research and Development, Duy Tan University, Da Nang, 550000, Viet 
      Nam.
FAU - Lin, Jing-Ying
AU  - Lin JY
AD  - Department of Medical Imaging and Radiological Science, Central Taiwan University 
      of Science and Technology, Taichung, 406, Taiwan.
FAU - Huang, Chih-Yang
AU  - Huang CY
AD  - Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi 
      Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; Graduate 
      Institute of Biomedical Sciences, China Medical University, Taichung, 404, 
      Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi 
      University of Science and Technology, Hualien, 970, Taiwan; Department of Medical 
      Research, China Medical University Hospital, China Medical University, Taichung, 
      404, Taiwan; Department of Biotechnology, Asia University, Taichung, 413, Taiwan. 
      Electronic address: cyhuang@mail.cmu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200731
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Allyl Compounds)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Antioxidants)
RN  - 0 (Sulfides)
RN  - 0ZO1U5A3XX (diallyl trisulfide)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - *Allyl Compounds/pharmacology
MH  - Animals
MH  - *Antibiotics, Antineoplastic/toxicity
MH  - Antioxidants
MH  - *Apoptosis
MH  - Brain
MH  - *Doxorubicin/toxicity
MH  - Humans
MH  - Inflammation
MH  - *Oxidative Stress/drug effects
MH  - Rats
MH  - *Sulfides/pharmacology
OTO - NOTNLM
OT  - Diallyl trisulfide (DATS)
OT  - Doxorubicin (DOX)
OT  - Inflammation
OT  - Oxidative stress
OT  - Tumor necrosis factor-alpha (TNF-alpha)
EDAT- 2020/08/04 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/04 06:00
PHST- 2020/04/02 00:00 [received]
PHST- 2020/07/08 00:00 [revised]
PHST- 2020/07/12 00:00 [accepted]
PHST- 2020/08/04 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/04 06:00 [entrez]
AID - S0891-5849(20)31154-0 [pii]
AID - 10.1016/j.freeradbiomed.2020.07.018 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 Nov 20;160:141-148. doi: 
      10.1016/j.freeradbiomed.2020.07.018. Epub 2020 Jul 31.