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

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.

Lycopene attenuates d-galactose-induced insulin signaling impairment by enhancing mitochondrial function and suppressing the oxidative stress/inflammatory response in mouse kidneys and livers

“…Food & Function animals. 31 In our present study, D-gal injection for 8 weeks blocked the Nrf2/HO-1/NQO-1 antioxidant defense pathway in mouse kidneys and livers. LYC supplementation increased the expression of Nrf2, HO-1 and NQO-1 and decreased the level of β-galactosidase.…”

“…Aging-related chronic liver and kidney diseases are common clinical conditions in the elderly and might cause increased mortality. 31 Elevated oxidative stress may trigger cell damage, thereby leading to accelerated aging and chronic degenerative diseases. 31 d -Gal is a reducing sugar that occurs naturally in the body and in many foods, 5 and mounting evidence demonstrates that high levels of d -gal injection for 6–8 weeks could result in the generation of ROS and subsequently accelerate oxidative stress and inflammation and induce the degeneration of numerous organs, such as the kidneys, liver and brain, which is similar to the characteristics of naturally aged animals.…”

“…32 Insulin exerts its activity via signal transduction pathways that start from the binding of insulin to the insulin receptor and trigger the tyrosine phosphorylation of IRS, activating downstream signaling intermediates such as PI3K and AKT, known as protein kinase B. 31,32 Then, p-AKT activates GSK3β, elicits the translocation of glucose transporters to the plasma membranes and promotes intracellular glucose intake. 32,33 However, the phosphorylation of IRS at serine 307 blocks phosphotyrosine protein phosphatases from dephosphorylating and inactivates IRS.…”

The Regulatory Network of Sturgeon Chondroitin Sulfate on Colorectal Cancer Inhibition by Transcriptomic and Proteomic Analysis

“…P21 is an inhibitor of cyclin-dependent kinase and multiple studies demonstrated a tumor suppressive role of P21 in tumorigene-sis [38,39]. The main mechanism of P21 to prevent cell cycle progression is to inhibit the expression of CCNE1 and PCNA, thereby reducing the expression of tumor growth factor and blocking the progress of cell cycle [40][41][42]. In addition to PCNA, we also focused on other two proteins, CCNE1 and P21, that are related to cell proliferation [36].…”

“…In our transcriptome dataset, a series of genes involved in apoptosis were found to be differentially regulated after SCS treatment. PI3K is an intracellular phosphatidylinositol kinase, which participates in the regulation of PI3K/Akt signaling pathway, facilitating cell proliferation, and promotes cell apoptosis [42]. Bad is known as a pro-apoptotic protein, which can trigger and promote cell apoptosis but is inactivated in cancer cells [22].…”