Laminaria japonica fucoidan ameliorates cyclophosphamide‐induced liver and kidney injury possibly by regulating Nrf2/HO‐1 and TLR4/NF‐κB signaling pathways

Abstract

BACKGROUND: During clinical practice, cyclophosphamide (CTX) can lead to liver and kidney injury in vivo. In this study, we established a liver and kidney injury model by injecting CTX (80 mg kg −1 d −1 ) into male ICR mice, and then mice were treated with saline and fucoidan (20 or 40 mg kg −1 ), respectively. Subsequently, the liver and kidney toxicity indices, the expression levels of malonic dialdehyde (MDA), inflammatory factors, and the main protein levels of the Nrf2/HO-1 and TLR4/NF-κB pathways were determined. RESULTS: Our results indicated that fucoidan could significantly decrease serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and urea (BUN) in the test group compared to the model group. Fucoidan administration caused reductions in MDA, interleukin-6 (IL-6), IL-1⊎, and tumor necrosis factor alpha (TNF-⊍) levels and improved superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the liver and kidney of CTXinduced mice. Fucoidan up-regulated the Nrf2/HO-1 pathway and enhanced the protein levels of Nrf2, HO-1, GCLM, and NQO1. Moreover, fucoidan down-regulated the TLR4/NF-κB pathway, as indicated by decreased levels of TLR4, NF-κB p65, NF-κB p50, and increased IκB⊍ level in liver and kidney tissues. CONCLUSION: Our studies suggest that fucoidan can ameliorate CTX-induced liver and kidney injury, potentially via upregulating the Nrf2/HO-1 pathway and inhibiting the TLR4/NF-κB pathway.

Hepatoprotective effect of water bamboo shoot (Zizania latifolia) extracts against acute alcoholic liver injury in a mice model and screening of bioactive phytochemicals

“…Many studies have shown the correlation between ROS, inflammatory cytokines, and NF‐κB signaling pathway (Li et al., 2021a). Simultaneously, some of nature products were confirmed to ameliorate liver injury by regulating NF‐κB signaling pathway (Tian et al., 2022; Zhao et al., 2021). For further screening of bioactive compounds of NE participating in NF‐κB pathway and alcoholic liver disease pathway against ALI, the compound‐target‐NF‐κB/alcoholic liver disease pathway network was established (Figure 3b and Table S2).…”

Phenethyl isothiocyanate protects against cyclophosphamide-induced nephrotoxicity via nuclear factor E2–related factor 2 pathway in rats

“…44 A study by Jung et al 45 also showed that NF-κB p65 acetylation is regulated through SIRT1, and they argued that SIRT1 activation may be a probable target in repairing cisplatin-induced kidney damage. In addition, Tian et al 46 informed that toxicity caused by CP was prevented via regulating the Nrf2/HO-1 and TLR4/ NF-κB signaling. We showed that in the CP-treated group, Nrf2 activation and SIRT1 levels decreased and NF-κB levels increased, whereas PEITC pretreatment caused the activation of Nrf2 and led to an elevation in the SIRT1 levels and inhibition of NF-κB.…”

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin

“…Sections were washed with phosphate buffer saline (PBS) three times after each step. Sections were then stained with diaminobenzidine chromogen solution (DAB), and counterstained with Mayer’s hematoxylin [ 45 , 46 ], then dehydrated and mounted. Negative control sections were obtained by omitting the primary antibodies.…”