Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.
Xiao-Qin DingTun-Yu JianYa-Nan GaiGuan-Ting NiuYan LiuXiu-Hua MengJing LiHan LyuBing-Ru RenJian ChenPublished in: Journal of agricultural and food chemistry (2022)
As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro , the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.
Keyphrases
- oxidative stress
- high fat diet
- chronic kidney disease
- high fat diet induced
- insulin resistance
- induced apoptosis
- diabetic rats
- end stage renal disease
- high glucose
- adipose tissue
- metabolic syndrome
- weight loss
- weight gain
- cell cycle arrest
- type diabetes
- dna damage
- poor prognosis
- protein kinase
- skeletal muscle
- signaling pathway
- cell proliferation
- cell death
- nlrp inflammasome
- physical activity
- simultaneous determination
- peritoneal dialysis
- gas chromatography