Study on the Protective Mechanism of Dihydromyricetin Against Aflatoxin B(1)-Induced Injury in Madin-Darby Canine Kidney Cells

二氢杨梅素对黄曲霉毒素B1诱导的Madin-Darby犬肾细胞损伤的保护机制研究

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Abstract

Aflatoxin B(1) (AFB(1)) is a common contaminant in canine diets that can cause significant damage to metabolic organs with prolonged exposure. Dihydromyricetin (DMY), a flavonoid compound abundant in Ampelopsis grossedentata, is widely used in functional foods due to its diverse biological activities. This study aimed to investigate the mechanism by which DMY alleviates AFB1-induced damage in MDCK cells. Four experimental groups were established: a control group with culture medium only (CON group), a group treated with 5 μg/mL AFB1 (AFB1 group), and two treatment groups treated with 5 μg/mL AFB1 combined with either 25 mmol/L or 50 mmol/L DMY-concentrations with more robust and stable protective effects than 100 mmol/L DMY, as confirmed by experimental screening. The results showed that AFB(1) significantly reduced MDCK cell viability at concentrations of 5-30 μg/mL (p < 0.01), while DMY at 25-100 mmol/L markedly improved cell viability (p < 0.01). AFB(1) treatment led to a significant increase in reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels, along with a reduction in superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.01). 25 mmol/L and 50 mmol/L DMY treatment reversed these effects, decreasing ROS, MDA, TNF-α, IL-6, and IL-1β levels while increasing SOD and CAT activities (p < 0.01). Furthermore, 25 mmol/L and 50 mmol/L DMY improved mitochondrial membrane potential (p < 0.01), counteracting AFB(1)'s inhibitory effects on autophagy-related proteins by promoting p-AMPK and Beclin-1 expression while inhibiting p-mTOR, p53, and p62 expression (p < 0.05). In conclusion, DMY mitigates AFB(1)-induced damage in MDCK cells by enhancing anti-inflammatory and antioxidant defenses and promoting autophagy, providing a theoretical foundation for future treatment strategies for canine kidney damage.

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