Lactoferrin protects against concanavalin A-induced liver injury in mice

Yin, Hao; Cheng, Linling; Agarwal, Chapla; Agarwal, Rajesh; Ju, Changqing

doi:10.1111/j.1478-3231.2009.02199.x

Cited by 15 publications

(10 citation statements)

References 38 publications

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“…To investigate whether genome editing occurs primarily in hepatocytes or in other cellular populations in the mouse liver, we perfused and digested the livers, isolated hepatic nonparenchymal cells (NPC) and enriched the hepatocyte population 33 . We found indels in total liver tissue and in the enriched hepatocyte population, but not in NPCs (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing

et al. 2017

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Efficient genome editing with Cas9–sgRNA in vivo has required the use of viral delivery systems, which have limitations for clinical applications. Translational efforts to develop other RNA therapeutics have shown that judicious chemical modification of RNAs can improve therapeutic efficacy by reducing susceptibility to nuclease degradation. Guided by the structure of the Cas9–sgRNA complex, we identify regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and we develop an optimal set of chemical modifications for in vivo applications. Using lipid nanoparticle formulations of these enhanced sgRNAs (e-sgRNA) and mRNA encoding Cas9, we show that a single intravenous injection into mice induces >80% editing of Pcsk9 in the liver. Serum Pcsk9 is reduced to undetectable levels, and cholesterol levels are significantly lowered about 35% to 40% in animals. This strategy may enable non-viral, Cas9-based genome editing in the liver in clinical settings.

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Section: Resultsmentioning

confidence: 99%

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing

et al. 2017

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“…Amelioration of ConA-induced liver injury symptoms has been associated with low IFN-γ levels 24 h after AIH induction in mice treated with lactoferrin (Yin et al 2010) or apolipoprotein A-II (Yamashita et al 2011). Our evaluations were performed later (after 7 days) and, for both Asc treatment protocols, there was also low IFN-γ production.…”

Section: Discussionmentioning

confidence: 99%

“…Autoimmune hepatitis (AIH) is a chronic progressive inflammatory disease, and the treatment is based on immunosuppression, which may culminate in disease remission (Yin et al 2010). However, there have been reports of therapeutic failure or toxicity of drugs that are currently used to treat this condition (Lemos et al 2007;Tu et al 2013;Czaja 2002).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

et al. 2014

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Adult worm extract from Ascaris suum (Asc) has immunosuppressive activity and elicits Th2/IL-4/IL-10 response. This study evaluated the prophylactic and therapeutic effect of Asc in a murine model of concanavalin A (ConA)-induced autoimmune hepatitis (AIH). BALB/c mice received ConA, iv, (20 mg/kg), and three groups of animals were formed: (1) AIH, received only ConA; (2) AIH + Asc prophylactic, treated with Asc (1 mg/ml), ip, 30 min before of the AIH; and (3) AIH + Asc therapeutic, treated with Asc 2 h after the AIH. Plasma transaminase and immunoglobulins (measured at 8 and 24 h and 7 days after treatment) and cytokine production (IL-4, IL-10, IL-13, and IFN-γ) by splenocytes upon ConA and Asc stimulus were compared. The livers were weighed and examined histologically. In the AIH group, there was an increase in liver weight, transaminase levels, and total immunoglobulins. These parameters were reduced by 8-24 h and 7 days in the prophylactic group, but in the therapeutic group, only on day 7. The survival rate of mice in the AIH group was 38.5%, compared to 67% in the therapeutic Asc group. The survival rate of the animals with AIH that were prophylactically treated with Asc was 100%. A decrease of cellular infiltration and high levels of IL-4, IL-10, and IL-13 were induced by Asc. An increase of liver fibrosis was also observed, but with less intensity with prophylactic treatment. Thus, the Ascaris components have an inhibitory effect on AIH, with an intense Th2 immune response.

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“…The results showed that lactoferrin inhibited acetaminophen-induced liver sinusoidal endothelial cell damage and improved hepatic congestion [ 65 ]. Their group also reported a hepatoprotective effect of lactoferrin against concanavalin A-induced hepatitis, which mimics the pathophysiology of human viral and autoimmune hepatitis [ 66 ]. In addition, it was reported that the oral or intravenous administration of lactoferrin exhibited potent hepatoprotection against obstructive jaundiced rats [ 67 ], hepatic amoebiasis model hamster [ 68 ], d -GalN/LPS-induced hepatitis model mice [ 69 ], carbon tetrachloride-induced hepatitis model mice [ 69 ], and chemical-induce rat liver fibrosis [ 70 ].…”

Section: Lactoferrinmentioning

confidence: 99%

Potential Use of Biological Proteins for Liver Failure Therapy

et al. 2015

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Biological proteins have unlimited potential for use as pharmaceutical products due to their various biological activities, which include non-toxicity, biocompatibility, and biodegradability. Recent scientific advances allow for the development of novel innovative protein-based products that draw on the quality of their innate biological activities. Some of them hold promising potential for novel therapeutic agents/devices for addressing hepatic diseases such as hepatitis, fibrosis, and hepatocarcinomas. This review attempts to provide an overview of the development of protein-based products that take advantage of their biological activity for medication, and discusses possibilities for the therapeutic potential of protein-based products produced through different approaches to specifically target the liver (or hepatic cells: hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) in the treatment of hepatic diseases.

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Lactoferrin protects against concanavalin A-induced liver injury in mice

Abstract: These findings indicate a great therapeutic potential of Lac in treating in treating inflammatory hepatitis and possibly other inflammatory diseases.

Cited by 15 publications

References 38 publications

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

Potential Use of Biological Proteins for Liver Failure Therapy

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