Troxerutin alleviates kidney injury in rats via PI3K/AKT pathway by enhancing MAP4 expression

Abstract

Background: Troxerutin is a flavonoid compound and possesses potential anti-cancer, antioxidant, and anti-inflammatory activities. Besides, cisplatin is one of the most widely used therapeutic agents, but the clinical uses of cisplatin are often associated with multiple side effects, among which nephrotoxicity is more common.
 Objective and design: This study explored the protective effects of troxerutin (150 mg kg−1 day−1 for 14 days) against cisplatin-induced kidney injury and the potential mechanism using Wistar rats as an experimental mammalian model.
 Results: We discovered that troxerutin could significantly alleviate cisplatin-induced renal dysfunction, such as increased levels of blood urea nitrogen and creatinine (P < 0.01), as well as improved abnormal renal tissue microstructure and ultrastructure. Additionally, troxerutin significantly decreased malondialdehyde (MDA), hydrogen peroxide (H2O2), NO, inducible nitric oxide synthase (iNOS) levels (P < 0.01), p-NF-κB p65/NF-κB p65, TNF-α, Pro-IL-1β, IL-6, B cell lymphoma-2 (Bcl-2)/Bcl-xl associated death promoter (Bad), Cytochrome C (Cyt C), Cleaved-caspase 9, Cleaved-caspase 3, and Cleaved-caspase 8 protein levels (P < 0.01) in the kidney tissues of cisplatin-treated rats; and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) activities (P < 0.01), IL-10, Bcl-2 protein levels (P < 0.01).
 Conclusion: These results suggested that the underlying mechanism might be attributed to the regulation of Phosphoinositide 3 kinase/Protein kinase B (PI3K/AKT) pathway via enhancing MAP4 expression to attenuate cellular apoptosis, alleviating oxidative stress and inflammatory response.

Troxerutin Exerts Anti-Pulmonary Fibrosis Activity in Nicotine-Induced Lung Fibrosis on Zebra Fish Model

“…The present finding reveals that troxerutin treated group in combination with nicotine decreased the levels of IL-10 and increased the IL-1β expression. Tong Xu Guan 21 reported that, troxerutin not only decreased the levels of TNF-α, NF-κB, IL-1β and IL-6 gene expression and but also increased IL-10 level. According to our study, troxerutin significantly increased LPO, MPO in the gill tissue homogenate and decreased enzymatic antioxidant levels (SOD, CAT) and also increased the NO generation.…”

Research on the pathological mechanism of rectal adenocarcinoma based on DNA methylation

“…[ 28 ] Ou et al found that the cAMP/PKA signaling pathway may inhibit the invasion of bladder cancer cells through targeted regulation of MAP4 phosphorylation. [ 29 ] MAP4 is widely involved in PI3K/AKT pathway in kidney injury [ 30 ] as well as in lumbar disc herniation-related diseases. [ 31 ]…”

“…[28] Ou et al found that the cAMP/ PKA signaling pathway may inhibit the invasion of bladder cancer cells through targeted regulation of MAP4 phosphorylation. [29] MAP4 is widely involved in PI3K/AKT pathway in kidney injury [30] as well as in lumbar disc herniation-related diseases. [31] YWHAG was mainly involved in the regulation of mitosis and the signal transduction between cells and other biological processes, and was closely related to tumor migration and proliferation.…”