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Fig. 2. Mechanisms of lactoferrin (LF) against AKI. Hyperoxia (FiO2 > 95 %) induces inflammation via ROS generation, MAPK and NF-κB activation. LF inhibits inflammation by reducing ROS generation and downregulating pro-inflammatory cytokines. PDC significantly increases NF-κB, IL-18, IL-4, and IGF-1 accompanied by kidney MDA and decreased GSH. Increased IL-4 leads to TNF-α expression and inflammation. IGF-1 enhances FoxO1 production, leading to tubular epithelial hyperplasia. Increased MDA leads to oxidative stress. PDC also increases Bax and caspase-3, resulting in apoptosis. LF prevents AKI by inhibiting PDC-induced inflammation, hyperplasia, apoptosis, and oxidative stress. Fe-NTA lowers the GSH content that causes oxidative stress. LF normalizes GSH and inhibits oxidative stress. Also, cisplatin causes cisplatin accumulation in the kidney that leads to tubular necrosis. LF decreases platinum content in the kidney, prevents cisplatin accumulation and inhibits tubular injury. AKI, acute kidney injury; Bax, BCL2 associated X; Fe-NTA, ferric nitrilotriacetate; FiO2, the fraction of inspired oxygen; FoxO1, forkhead box protein O1; GSH, glutathione; IGF-1, insulin-like growth factor-1; IL, interleukin; MDA, malondialdehyde; NF-κB, nuclear factor kappa B; PCNA, proliferating cell nuclear antigen; PDC, potassium dichromate; TNF-α, tumor necrosis factor alpha; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species.
Korean J Physiol Pharmacol 2022;26:1-13 https://doi.org/10.4196/kjpp.2022.26.1.1
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