A dimethylnitrosamine-induced model of cirrhosis and portal hypertension in the rat

Jenkins, S. A.; Grandison, Alistair S.; Baxter, J. N.; Day, David W.; Taylor, Imogen; Shields, R.

doi:10.1016/s0168-8278(85)80747-9

Cited by 120 publications

(110 citation statements)

References 3 publications

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“…It is widely used in experimental animals, such as rats and mice 10,[12][13][14] to create a low-mortality and reproducible model of liver fibrosis [15][16][17][18] that is characterized in the early stages by centrilobular injury, followed by perivenular fibrosis and the formation of septa with the development of micronodular cirrhosis after 3 weeks of treatment. In this model, collagen accumulation is preceded by hepatic stem cell proliferation, which accumulates where fibrous septa will later appear, 19 and is associated with increased mRNA expression of types I, III and IV procollagen.…”

Section: Establishment Of a Mouse Hepatic Fibrosis Modelmentioning

confidence: 99%

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

et al. 2008

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The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis. Gene Therapy (2008) 15, 990-997;

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Section: Establishment Of a Mouse Hepatic Fibrosis Modelmentioning

confidence: 99%

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

et al. 2008

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“…The sugar content and number of PDP groups coupled to M6P-BSA or BSA was determined as described previously. TFO modified with sulfhydryl group at 3' end was first treated with DTT to generate a 3'-thiol functional group and then reacted with 2.5 mg of (M6P) 20 -BSA-PDP in glycine buffer. The product was eluted with PBS on a G 75 column (1×25 cm).…”

Section: Synthesis and Characterization Of M6p-bsa-tfomentioning

confidence: 99%

“…To maximize TFO delivery to the liver in general and to HSCs in particular, we recently synthesized mannose 6-phosphate bovine serum albumin (M6P-BSA) and conjugated to type α1(I) collagen gene promoter specific TFO via a disulfide bond (16). Following tail vein injection into normal rats, (M6P) 20 -BSA-33 P-TFO rapidly cleared from the circulation and accumulated mainly in the liver. TFO concentration residing in the HSCs was shown to be much higher with (M6P) 20 -BSA-33 P-TFO than that with 33 P-TFO (1093 vs 215 ng/mg cell protein).…”

Section: Introductionmentioning

confidence: 99%

“…Following tail vein injection into normal rats, (M6P) 20 -BSA-33 P-TFO rapidly cleared from the circulation and accumulated mainly in the liver. TFO concentration residing in the HSCs was shown to be much higher with (M6P) 20 -BSA-33 P-TFO than that with 33 P-TFO (1093 vs 215 ng/mg cell protein).…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we determined the cellular and nuclear uptake of (M6P) 20 -BSA-33 P-TFO by HSC-T6 cells, which is an immortalized rat hepatic cell line. The effect of M6P-BSA-TFO on type α1(I) collagen gene transcription has also been determined by real time RT-PCR.…”

Section: Introductionmentioning

confidence: 99%

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Receptor-Mediated Hepatic Uptake of M6P−BSA-Conjugated Triplex-Forming Oligonucleotides in Rats

Cheng

Guntaka

et al. 2006

Bioconjugate Chem.

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Excessive production of extracellular matrix, predominantly type I collagen results in liver fibrosis. Earlier we synthesized mannose 6-phosphate-bovine serum albumin (M6P-BSA) and conjugated to the type I collagen specific triplex forming oligonucleotide (TFO) for its enhanced delivery to hepatic stellate cells (HSCs), which is the principle liver fibrogenic cell. In this report, we demonstrate a time-dependent cellular uptake of M6P-BSA-33 P-TFO by HSC-T6 cells. Both cellular uptake and nuclear deposition of M6P-BSA-33 P-TFO were significantly higher than those of 33 P-TFO, leading to enhanced inhibition of type I collagen transcription. Following systemic administration into rats, hepatic accumulation of M6P-BSA-33 P-TFO increased from 55% to 68% with the number of M6P per BSA from 14 to 27. Unlike 33 P-TFO, there was no significant decrease in the hepatic uptake of (M6P) 20 -BSA-33 P-TFO in fibrotic rats. Prior administration of excess M6P-BSA decreased the hepatic uptake of (M6P) 20 -BSA-33 P-TFO from 66% to 40% in normal rats, and from 60% to 15% in fibrotic rats, suggesting M6P/insulin-like growth factor II (M6P/IGF-II) receptor-mediated endocytosis of M6P-BSA-33 P-TFO by HSCs. Almost 82% of the total liver uptake in fibrotic rats was contributed by HSCs. In conclusion, by conjugation with M6P-BSA, the TFO could be potentially used for the treatment of liver fibrosis.

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Experimental Models of Cirrhosis and Ascites

Clària¹,

Jiménez²

2005

Ascites and Renal Dysfunction in Liver Disease

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A dimethylnitrosamine-induced model of cirrhosis and portal hypertension in the rat

Cited by 120 publications

References 3 publications

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

Receptor-Mediated Hepatic Uptake of M6P−BSA-Conjugated Triplex-Forming Oligonucleotides in Rats

Experimental Models of Cirrhosis and Ascites

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