Table. 1.

Kidney protective effects of lactoferrin

Experimental models Lactoferrin doses Disease models Pathobiology involved Major research outcome Molecular markers Reference
Hyperoxia (FiO2 > 95%) exposed NF-κB-Luc+/+ mice 150 mg/kg or 300 mg/kg once daily for 2 weeks AKI Inflammation, and oxidative stress Attenuates hyperoxia-induced kidney systemic inflammation ↓ROS, ↓p-MAPK, ↓NF-κB, ↓IL-6, ↓IL-1β, ↓TNF-α, [19]
PDC injected Wistar rats (200 mg/kg/day, p.o.) or (300 mg/kg/day, p.o.) for 14 days AKI Oxidative stress, inflammation, and apoptosis Protective effects against PDC-induced acute nephrotoxicity ↓IL-18, ↓IL-4, ↓TNF-α, ↓NF-κB, ↓IGF-1, ↓FoxO1, ↑GSH, ↓MDA, ↓PCNA, ↓Bax, ↓Caspase3, ↓serum urea, ↓creatinine [11]
Cisplatin injected Wistar rats (300 mg/kg) daily for six days AKI Necrosis, and ischemia Protects kidney against Cisplatin-induced nephrotoxicity ↓BUN, ↓creatinine [45]
Fe-NTA injected Wistar rats (0.05%, w/w) for 4 weeks AKI Oxidative stress Protects rats from iron-induced kidney tubular injury ↓BUN, ↓creatinine, ↑GSH, ↑GSH peroxidase, ↑GSH reductase [46]
Folic acid injected C57BL/6 mice (2 mg/mouse) and (4 mg/mouse) two times per week for five weeks CKD Autophagy dysfunction, apoptosis, and fibrosis Suppresses fibrosis by inhibiting apoptosis and inducing autophagy ↑LC3, ↓cleaved Caspase3 ↓α-SMA, ↓BUN, ↓creatinine [23]
High fat and salt-loaded SHRSP rats 20% kcal LF diet for eight weeks CKD Inflammation Protective effects against kidney damage ↓OPN, ↓renin, ↓MCP-1, ↓IL-6, ↓urine albumin, ↓creatinine [54]
H2O2 treated HK-2 cells 100–200 µg/ml for 6 hours CKD/ oxidative damage Oxidative stress, autophagy dysfunction, and apoptosis Inhibits oxidative stress-induced cell death and apoptosis by augmenting autophagy ↑p-AMPK, ↓p-AKT, ↓p-mTOR, ↑LC3-II, ↑beclin 1, ↑LTF, ↓Bax, ↓cleaved Caspase3, ↓cleaved Caspase9 [23]
TGF-β1 treated HK-2 cells 100–200 µg/ml for 24 hours CKD/kidney fibrosis Fibrosis Inhibits TGF-β1-induced fibrosis in HK-2 cells ↓PAI-1, ↓CTGF, ↓collagen I [23]

AKI, acute kidney injury; AKT, protein kinase B; AMPK, AMP-activated protein kinase; Bax, BCL2 associated X; BUN, blood urea nitrogen; CKD, chronic kidney disease; CTGF, connective tissue growth factor; FiO2, the fraction of inspired oxygen; Fe-NTA, ferric nitrilotriacetate; FoxO1, forkhead box protein O1; GSH, glutathione; HK-2, human kidney 2; IGF-1, insulin-like growth factor-1; IL, interleukin; LC3, light chain 3; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; NF-κB, nuclear factor kappa B; OPN, osteopontin; PAI-1, plasminogen activator inhibitor-1; PCNA, proliferating cell nuclear antigen; PDC, potassium dichromate; ROS, reactive oxygen species; SHRSP, stroke-prone spontaneously hypertensive rat; TGF-β1, transforming growth factor-beta 1; TNF-α, tumor necrosis factor-alpha; mTOR, mechanistic target of rapamycin; α-SMA, alpha-smooth muscle actin.

Korean J Physiol Pharmacol 2022;26:1-13 https://doi.org/10.4196/kjpp.2022.26.1.1
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