Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Feng, Lei; Cai, Lei; He, Guolin; Weng, Jun; Yang, Li; Pan, Mingxin; Jiang, Zhiying; Peng, Qing; Gao, Yi

doi:10.3748/wjg.v23.i42.7572

Cited by 12 publications

(16 citation statements)

References 32 publications

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“…Numerous cytokines such as interleukin family, colony-stimulating factor and chemokines formed a complex, overlapping communication network. Based on our data, significant increase of inflammatory markers as IL-1β, IL-6, and TNF-α was detected, which was consistent with previous studies and showed to be positively correlated with liver cell necrosis (Pan et al, 2016; Feng et al, 2017). Higher levels of colony stimulating factors including GM-CSF, M-CSF, and G-CSF were found in rats with D-GalN injection.…”

Section: Discussionsupporting

confidence: 92%

Pretreatment With Bacillus cereus Preserves Against D-Galactosamine-Induced Liver Injury in a Rat Model

et al. 2019

Front. Microbiol.

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Bacillus cereus ( B. cereus ) functions as a probiotic in animals, but the underlying mechanisms remain unclear. We aim to evaluate the protective effects and definite mechanism by which orally administered B. cereus prevents D-galactosamine (D-GalN)-induced liver injury in rats. Twenty-one Sprague–Dawley rats were equally assigned into three groups ( N = 7 animals per group). B. cereus ATCC11778 (2 × 10 9 colony-forming units/ml) was administered to the B. cereus group via gavage, and phosphate-buffered saline was administered to the positive control (PC) and negative control (NC) groups for 2 weeks. The PC and B. cereus groups received 1.1 g/kg D-GalN via an intraperitoneal injection to induce liver injury. The blood, terminal ileum, liver, kidney and mesenteric lymph nodes (MLNs) were collected for histological examinations and to evaluate bacterial translocation. Liver function was also determined. Fecal samples were collected for deep sequencing of the 16S rRNA on an Illumina MiSeq platform. B. cereus significantly attenuated D-GalN-induced liver injury and improved serum alanine aminotransferase (ALT) and serum cholinesterase levels ( P < 0.05 and P < 0.01, respectively). B. cereus modulated cytokine secretion, as indicated by the elevated levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in both the liver and plasma ( P < 0.05 and P < 0.01, respectively) and the substantially decreased levels of the cytokine IL-13 in the liver ( P < 0.05). Pretreatment with B. cereus attenuated anoxygenic bacterial translocation in the veins ( P < 0.05) and liver ( P < 0.05) and upregulated the expression of the tight junction protein 1. The gut microbiota from the B. cereus group clustered separately from that of the PC group, with an increase in species of the Ruminococcaceae and Peptococcaceae families and a decrease in those of the Parabacteroides , Paraprevotella , and Desulfovibrio families. The potential probiotic B. cereus attenuated liver injury by restoring the gut flora balance and enhancing the intestinal barrier function.

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Section: Discussionsupporting

confidence: 92%

Pretreatment With Bacillus cereus Preserves Against D-Galactosamine-Induced Liver Injury in a Rat Model

et al. 2019

Front. Microbiol.

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“…At present, there are two main methods to construct ALF animal models: drug model [7,22,23] and surgical model [6,24,25]. Compared with the drug model, surgical ALF animal model requires high surgical techniques, and surgical trauma affects the pathophysiology of liver, which is different from the physiological and biochemical manifestations of clinical ALF.…”

Section: Discussionmentioning

confidence: 99%

“…The most common used drugs for inducing ALF mainly include D-galactosamine (D-gal) [7,22], acetaminophen (APAP) [26][27][28][29], thioacetamide (TAA) [30], and carbon tetrachloride (CCl 4 ) [31]. In most drug models of ALF, there are nephrotoxicity, cardiotoxicity and other organ damage besides hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Acute Liver Failure Model in Tibet Miniature Pig and Verified by a Non-bioartificial Liver

Liu

Wang

et al. 2021

Preprint

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Background and aims Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality. Animal model is very important to research ALF. This study aimed to establish a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF and verified by a non-bioartificial liver (NBAL).Methods Thirteen Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after central venous catheterization, then D-galactosamine (D-gal) at 0.45, 0.40 and 0.35g/kg body weight were injected through the central venous catheter in group A, B, C. While in group D, D-gal at 0.35g/kg body weight was injected and treated by a NBAL at 48 h after D-gal administration. Vital signs, blood index values were recorded at every 12 h after D-gal administration and every 2 h during NBAL treatemnt. Meanwhile, clinical manifestations, survival times and results of H&E staining, Tunel, Ki67, Masson assays and Picrosirius red staining were performed.Results Tibet miniature pigs developed different degrees of debilitation, loss of appetite and jaundice after D-gal administration. Survival times of groups A, B, C and D were 39.7±5.9 h, 53.0±12.5 h, 61.3±8.1 h and 61±7 h, respectively. Blood levels of ALT, AST, TBIL, Cr, BUN, Amm, PT and inflammation factors (such as TNF-α, IL-1β, IL-6) levels significantly increased compared with baseline in different groups (Ps < 0.05). Pathological results showed obvious liver cell necrosis positively correlated to the dose of D-gal. However, the NBAL did not increase the survival times of ALF, neither Amm and liver cell necrosis, it just decreased some biochemistry indexes (such as TBIL, ALT, AST).Conclusions: We successfully established a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF, the NBAL did not improve the survival times of ALF and we think the dosage of 0.35 g/kg is optimal.

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“…D-GalN is the most commonly used hepatotoxic agent in large animal models of ALF, in which D-GalN is administered directly through the jugular or central vein. 0.5–1.5 g kg −1 D-GalN can induce fulminant hepatic failure in pigs [ 8 , 53 , 54 ], while 0.2–0.3 g kg −1 D-GalN is used for constructing D-GalN-related cynomolgus monkey model of ALF [ 55 , 56 ]. LPS triggers the activation of Kupffer cells and production of tumor necrosis factor-α (TNF-α), resulting in inflammatory necrosis of hepatocytes.…”

Section: Mechanism Of Nanomedicines For Acute Liver Failure Therapymentioning

confidence: 99%

Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure

Jin

Wang

et al. 2020

Nano-Micro Lett.

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Highlights This review focuses on the therapeutic mechanisms, targeting strategies of various nanomaterials in acute liver failure, and recent advances of diverse nanomaterials for acute liver failure therapy, diagnosis, and imaging. This review provides an outlook on the applications of nanomaterials, especially on the new horizons in acute liver failure therapy, and inspires broader interests across various disciplines. Abstract Acute liver failure (ALF), a fatal clinical disease featured with overwhelming hepatocyte necrosis, is a grand challenge in global health. However, a satisfactory therapeutic option for curing ALF is still absent, other than liver transplantation. Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF. The liver can sequester most of nanoparticles from blood circulation, which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases. Nanobiomaterials can enhance the bioavailability of free drugs, thereby significantly improving the therapeutic effects in ALF. Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells. In addition, stimuli-responsive, optical, or magnetic nanomaterials exhibit great potential in the therapeutical, diagnostic, and imaging applications in ALF. Therefore, therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy, diminish adverse systemic effects, and offer a multifunctional theranostic platform. Nanobiomaterial holds excellent significance and prospects in ALF theranostics. In this review, we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF. We highlight recent developments of diverse nanomedicines for ALF therapy, diagnosis, and imaging. Furthermore, the challenges and future perspectives in the theranostics of ALF are also discussed.

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Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Cited by 12 publications

References 32 publications

Pretreatment With Bacillus cereus Preserves Against D-Galactosamine-Induced Liver Injury in a Rat Model

Pretreatment With Bacillus cereus Preserves Against D-Galactosamine-Induced Liver Injury in a Rat Model

Establishment of Acute Liver Failure Model in Tibet Miniature Pig and Verified by a Non-bioartificial Liver

Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure

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