PMID- 37871339
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231102
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 71
IP  - 43
DP  - 2023 Nov 1
TI  - Sodium Sulfite-Triggered Hepatocyte Ferroptosis via mtROS/Lysosomal Membrane 
      Permeabilization-Mediated Lysosome Iron Efflux.
PG  - 16310-16322
LID - 10.1021/acs.jafc.3c06085 [doi]
AB  - Sodium sulfite is a widely used preservative in the food industry. Ferroptosis 
      has been a newly discovered form of iron-dependent oxidative cell death in recent 
      years. However, the potential connection between sodium sulfite and ferroptosis 
      has not been explored. In our study, we observed the abnormal expression of 
      ferroptosis marker protein in vivo, suggesting that sodium sulfite caused 
      ferroptosis in vivo. Next, our study revealed that sodium sulfite caused the 
      overproduction of mitochondrial reactive oxygen species (mtROS) in the AML-12 
      cells. It is well established that reactive oxygen species (ROS) can induce 
      lysosomal membrane permeabilization. After lysosomal membrane permeabilization 
      occurs, the outflow of Fe(2+) in lysosomes triggers the Fenton reaction and 
      subsequently results in the increase of intracellular ROS level, which is closely 
      related to ferroptosis. As speculated, acridine orange (AO) staining and 
      LysoTracker red staining showed that sodium sulfite-induced lysosomal membrane 
      permeabilization could be alleviated by mtROS scavenger TEMPO. In addition, 
      TEMPO, lysosomal stabilizer mannose, and lysosomal iron chelator deferoxamine 
      (DFO) inhibited sodium sulfite-induced ferroptosis. Overall, the results showed 
      that sodium sulfite induced lysosomal iron efflux through the mtROS-lysosomal 
      membrane permeabilization pathway and eventually led to ferroptosis. Our study 
      might provide a new mechanism for the hepatotoxicity of sodium sulfite and a 
      theoretical basis for the risk assessment of sodium sulfite as a food additive.
FAU - Liu, Meitong
AU  - Liu M
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
FAU - Lu, Jing
AU  - Lu J
AUID- ORCID: 0000-0002-8323-3082
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
AD  - Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, 
      Jilin University, Changchun, Jilin 130062, China.
FAU - Chen, Yuelin
AU  - Chen Y
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
FAU - Zhang, Shengzhuo
AU  - Zhang S
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
FAU - Guo, Jiakang
AU  - Guo J
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
FAU - Guan, Shuang
AU  - Guan S
AUID- ORCID: 0000-0003-4948-167X
AD  - College of Food Science and Engineering, Jilin University, Changchun, Jilin 
      130062, China.
AD  - Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, 
      Jilin University, Changchun, Jilin 130062, China.
LA  - eng
PT  - Journal Article
DEP - 20231023
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Reactive Oxygen Species)
RN  - E1UOL152H7 (Iron)
RN  - VTK01UQK3G (sodium sulfite)
SB  - IM
MH  - *Ferroptosis
MH  - Reactive Oxygen Species/metabolism
MH  - Iron/metabolism
MH  - Hepatocytes/metabolism
MH  - Lysosomes/metabolism
OTO - NOTNLM
OT  - ferroptosis
OT  - iron homeostasis
OT  - lysosomal membrane permeabilization
OT  - mtROS
OT  - sodium sulfite
EDAT- 2023/10/23 18:42
MHDA- 2023/11/02 12:42
CRDT- 2023/10/23 17:53
PHST- 2023/11/02 12:42 [medline]
PHST- 2023/10/23 18:42 [pubmed]
PHST- 2023/10/23 17:53 [entrez]
AID - 10.1021/acs.jafc.3c06085 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2023 Nov 1;71(43):16310-16322. doi: 10.1021/acs.jafc.3c06085. 
      Epub 2023 Oct 23.