Lactoferrin Increases Antioxidant Activities and Ameliorates Hepatic Fibrosis in Lupus-Prone Mice Fed with a High-Cholesterol Diet

Abstract

Lactoferrin (LF) has beneficial effects against various diseases. However, the effects of LF on liver fibrosis in systematic lupus erythematosus (SLE) are unknown. In this study, NZB/W F1 mice were utilized to investigate the effects of LF on SLE. Experiments reveal that LF significantly increases glutathione and 1,1-diphenyl-2-picryl-hydrazyl levels and significantly decreased malondialdehyde levels in both serum and liver in NZB/W F1 mice. LF also lowered matrix metalloproteinase-9 activity and liver inflammatory indices, such as aminotransferase and alanine aminotransferase. Notably, significantly decreased expression of fibrotic related molecules, including transforming growth factor (TGF)-β1, tumor necrosis factor-α, interleukin-1β, and TGF-β1 receptor, were observed in the livers of NZB/W F1 mice that had been treated with LF. Significantly, suppressed Smad2/3 signaling, α-smooth muscle actin, and collagen deposition were also detected. These findings reveal that LF has beneficial effects on SLE by increasing antioxidant activities and ameliorating liver inflammation and fibrosis, suggesting the therapeutic effectiveness of LF against SLE.

Effects of FGF21‐secreting adipose‐derived stem cells in thioacetamide‐induced hepatic fibrosis

“…Among the secreted proteins upregulated in the FGF21_ADSCs CM, we noted that α‐LA and LTF might be involved in the inhibition of fibrogenic activity. α‐LA and LTF have a liver protective and anti‐fibrotic effect, respectively . We confirmed that α‐LA or LTF treatment inhibited TGF‐β‐induced α‐SMA and Col1a1 expression in LX‐2 cells.…”

“…α-LA and LTF have a liver protective and anti-fibrotic effect, respectively. 10,11 We confirmed that α-LA or LTF treatment inhibited TGF-β-induced α-SMA and Col1a1 expression in LX-2 cells.…”

“…Among the proteins that were increased over 2‐fold (Figure S4), we chose lactotransferrin (LTF) and α‐lactoalbumin (α‐LA) for further analysis, because they inhibit liver fibrosis 10, 11. Western blot analysis showed that LTF and α‐LA secretion was significantly increased in FGF21_ADSCs CM compared with Empty_ADSCs CM (Figure 2G).…”

“…Secretome analysis by mass spectrometry identified 365 proteins in FGF21_ADSCs CM, of which 33 showed a significant increase and 39 showed a significant decrease as compared with Empty_ADSCs CM (data not shown). Among the proteins that were increased over 2‐fold (Figure ), we chose lactotransferrin (LTF) and α‐lactoalbumin (α‐LA) for further analysis, because they inhibit liver fibrosis . Western blot analysis showed that LTF and α‐LA secretion was significantly increased in FGF21_ADSCs CM compared with Empty_ADSCs CM (Figure G).…”

Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-κB Signaling in a Rat Non-Alcoholic Steatohepatitis Model

“…With regard to the liver, decreased IL-1β by LF leads to the inhibition of carbon tetrachloride-induced hepatitis in a rat model [ 18 ]. Another report suggests that LF reduced the expression of TGF-β1, IL-1β, and TNF-α and suppressed liver fibrosis in a rat systemic lupus erythematosus model [ 19 ]. The anti-tumor abilities of LF have also been described in various cancer cell lines, such as those of the breast [ 20 ], stomach [ 21 ], head, and neck [ 22 ].…”