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. 2021 Aug;35(8):4411-4424.
doi: 10.1002/ptr.7142. Epub 2021 May 24.

The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on D-galactose-induced liver and kidney aging and injury

Ji-Yue Sha  1 , Jian-Hao Li  1   2 , Yan-Dan Zhou  1 , Jia-Yu Yang  1 , Wei Liu  1 , Shuang Jiang  1 , Ying-Ping Wang  1   3 , Rui Zhang  1 , Peng Di  1   3 , Wei Li  1   3
Affiliations

The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on D-galactose-induced liver and kidney aging and injury

Ji-Yue Sha et al. Phytother Res. 2021 Aug.

Abstract

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.

Keywords: D-galactose; PI3K/Akt pathway; apoptosis; maltol; oxidative stress; p53/p21/p16.

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