ReferenceID 1779

Autophagy and mitochondrial dynamics contribute to the protective effect of diosgenin against 3-MCPD induced kidney injury

Chem Biol Interact

3-Chloro-1, 2-propanediol (3-MCPD) is a widespread food contaminant with kidney as the main target organ. The exploration of ingredients as intervention strategy towards 3-MCPD induced nephrotoxicity is needed. Diosgenin

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Reference Id
1779
Evidence Id
18369
Core Evidence Id
18369
Source Reference Id
3551
Herb2 Reference Id
HBREF004348
Subject Paper Key
HBIN024164_35149085
Pubmed Id
35149085
Doi
10.1016/j.cbi.2022.109850
Paper Title
Autophagy and mitochondrial dynamics contribute to the protective effect of diosgenin against 3-MCPD induced kidney injury
Paper Abstract
3-Chloro-1, 2-propanediol (3-MCPD) is a widespread food contaminant with kidney as the main target organ. The exploration of ingredients as intervention strategy towards 3-MCPD induced nephrotoxicity is needed. Diosgenin (DIO) is a steroidal saponin presented in several plants and foods. Here we assessed whether DIO attenuates nephrotoxicity induced by 3-MCPD using Human embryonic kidney 293 (HEK293) cells and Sprague-Dawley (SD) rats. The results showed that DIO (2, 6, 8 μM) increased cell viability and exerted inhibitory effect on caspase 3 and caspase 9 activities. Histological examination of rats showed that 15 mg/kg bw DIO ameliorated renal pathological changes caused by 3-MCPD (30 mg/kg bw). DIO also induced autophagy and the blockade of autophagy with 3-Methyladenine (3-MA) aggravated mitochondrial apoptosis induced by 3-MCPD in HEK293 cells. Moreover, treatment with DIO caused an increase in p-LKB1/LKB1 and p-AMPK/AMPK expressions and a decrease in p-mTOR/mTOR, p-ULK1(Ser 757 ), p-P70S6K and p-4EBP1 expressions. Additionally, DIO improved mitochondrial dynamics mainly through inhibiting the relocation of DRP1 on mitochondria and enhancing MFN1 and MFN2 expressions. In conclusion, our study demonstrated for the first time that DIO protected against kidney injury induced by 3-MCPD through the induction of autophagy via LKB1-AMPK-mTOR pathway and the improvement of mitochondrial fission and fusion.
Journal
Chem Biol Interact
Publish Year
2022
Experiment Subject
rat; human; hek293 cells; human embryonic kidney 293 (hek293) cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Kidney Injury
Paper Title Cn
Paper Title En
Autophagy and mitochondrial dynamics contribute to the protective effect of diosgenin against 3-MCPD induced kidney injury
Bilingual Status
semi_complete