Lipoxin-A4 in the rabbit model of atherosclerosis and liver steatosis

BACKGROUND: Obesity is a global health problem that is associated with wide range of diseases, including atherosclerosis and Nonalcoholic fatty liver (NAFL) disease. Hepatic inflammation can cause cirrhosis, hepatic decompensation (liver failure) and cancer. Recent research now looks at the chronic systemic effects and inter-organ communication between atherosclerosis potentially promoting the development of NAFL. The resolution of inflammation is regulated naturally in the body by specialized pro-resolving mediators (SPMs). Immunoresolvents like ⍹6-derived Lipoxin A4 are suggested as a therapeutic strategy to overcome chronic inflammation and disease. In this study we investigated the therapeutic potential of Lipoxin A4 (LXA4) in cholesterol fed rabbit model of hypercholesterolemia, with atherosclerotic plaques and confined vascular endothelial injury and its effect on the progression of NAFL. OBJECTIVE: This is a continuation of studies pioneered in the Hamilton lab and an extension of the recent study by Taylor et. al in 201811 linking aortic plaque and liver disease. We will now investigate the therapeutic potential of Lipoxin A4 on lipid-rich atherosclerotic plaques in cholesterol fed rabbits and its effect on the progression of NAFL to NASH. METHODS: In vivo magnetic resonance imaging (MRI) measured aortic atherosclerotic inflammation (with plaque Gd-enhancement), plaque size (vessel wall area), and composition, within rabbits fed normal chow or a 1% cholesterol-enriched diet. Biomarkers in the blood were monitored in the rabbits, with follow-up by histology, which included Masson’s trichrome staining. Light Microscopy was used for liver imaging. Ex vivo MRI, T1W imaging was used to quantify VWA (vessel wall area), with Image J programming. RESULTS: Cholesterol-fed rabbits with and without aortic injury developed hypercholesterolemia, NAFL, and atherosclerotic plaques in the aorta. Elevated plasma gamma-glutamyl transferase (GGT; p =0.014) and the ratio of liver enzymes aspartate and alanine aminotransferases (AST/ALT; p = 0.033) confirmed the progression of steatosis to non-alcoholic steatohepatitis (NASH). Histological images showed less fibrosis in those rabbits fed 1% CHOL diet with injury treated with LipoxinA4, when compared to 1% CHOL diet and injury alone. The plasma biomarkers showed a decrease in cholesterol (79%) and triglycerides (49.9%) in those rabbits given LXA4 therapy. The LXA4 treated 1% CHOL diet with injury group showed a marked decrease in the aorta vessel wall area when compared to the 1% CHOL diet with injury, without treatment; as seen in ex vivo, MRI T1W imaging. CONCLUSION: Lipoxin implementation in cholesterol fed rabbits that have localized regions of highly inflamed aortic atherosclerotic plaques, may contribute to the attenuation on the progression of NAFL to NASH as seen in histology and plasma biomarkers including; cholesterol and triglycerides. Lipoxin as a therapeutic has an effect on treating atherosclerotic plaques and attenuating atherosclerosis progression

Rabbit Model of Retinoblastoma

We created a rabbit model of retinoblastoma and confirmed the tumor clinically and histopathologically. Seventeen New Zealand rabbits were immunosuppressed with cyclosporin A at doses of 10–15 mg/kg. At day 3, the animals received a 30 μl subretinal injection of 1 × 106 cultured WERI retinoblastoma cells. Digital fundus images were captured before euthanasia, and the eyes were submitted for histopathology. Retinoblastoma cells grew in all the inoculated eyes and established a tumor under the retina and/or in the vitreous. New blood vessels in the tumor were observed starting at week 5. Cuffs of viable tumor cells surrounded the blood vessels with regions of necrosis present at 70–80 μm from nutrient vessels. Occasional tumor seeds in the vitreous histologically exhibited central necrosis. This rabbit model demonstrated similar fundus appearance and pathologic features to human retinoblastoma and may be used as a model to test various routes of drug delivery for retinoblastoma

The Temporal Expression of Adipokines During Spinal Fusion

Background Context Adipokines are secreted by white adipose tissue and have been associated with fracture healing. Our goal was to report the temporal expression of adipokines during spinal fusion in an established rabbit model. Purpose Our goal was to report the temporal expression of adipokines during spinal fusion in an established rabbit model. Study Design The study design included a laboratory animal model. Methods New Zealand white rabbits were assigned to either sham surgery (n=2), unilateral posterior spinal fusion (n=14), or bilateral posterior spinal fusion (n=14). Rabbits were euthanized 1–6 and 10 weeks out from surgery. Fusion was evaluated by radiographs, manual palpation, and histology. Reverse transcription-polymerase chain reaction on the bone fusion mass catalogued the gene expression of leptin, adiponectin, resistin, and vascular endothelial growth factor (VEGF) at each time point. Results were normalized to the internal control gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (2^ΔCt), and control bone sites (2^ΔΔCt). Quantitative data were analyzed by two-factor analysis of variance (p\u3c.05). Results Manual palpation scores, radiograph scores, and histologic findings showed progression of boney fusion over time (p Conclusions Leptin expression is likely associated with the maturation phase of bone fusion. Adiponectin and resistin may play a role early on during the fusion process. Our results suggest that leptin expression may be upstream of VEGF expression during spinal fusion, and both appear to play an important role in bone spinal fusion

Osseointegration of Wrapped Dental Implants in Rabbits

Edentulous patients (those lacking teeth) require one of two approaches to augmentation: inserting a vertical bone graft, or subperiosteally anchoring a device on which an implant can be attached. Bone grafts have had unpredictable results and can undergo resorption over time, compromising implant stability and success. As of the subperiosteal approach, current materials have not proven to directly integrate with the bone, in a process termed osseointegration. Therefore, we used additive manufacturing to create a Ti6Al4V alloy surface with a specific roughness to determine if it would be osseoinductive in a challenging rabbit model over six weeks

A rabbit model for liver fibrosis

This experiment was carried out to investigate the role of cells participating in fibrosis induced by bile-duct ligation in rabbits. Histologically, bile stasis, degeneration and focal necrosis of hepatocytes, bile ductular proliferation, and an increase of the connective tissue were seen in periportal regions. Immunohistochemically, it was found that the majority of cells observed in the fibrosis regions were positive cells (spindle cells) for alpha-smooth muscle actin (ASMA). It is suggested that the spindle cells, probably transforming from Ito cells or myofibroblasts, play an important role in the pathogenesis ofhepatic fibrosis

Is intra-abdominal hypertension a missing factor that drives multiple organ dysfunction syndrome?

In a recent issue of Critical Care, Cheng and colleagues conducted a rabbit model study that demonstrated that intra-abdominal hypertension (IAH) may damage both gut anatomy and function. With only 6 hours of IAH at 25 mmHg, these authors observed an 80% reduction in mucosal blood flow, an exponential increase in mucosal permeability, and erosion and necrosis of the jejunal villi. Such dramatic findings should remind all caring for the critically ill that IAH may severely damage the normal gut barrier functions and thus may be reasonably expected to facilitate bacterial and mediator translocation. The potential contribution of IAH as a confounding factor in the efficacy of selective decontamination of the digestive tract should be considered

Effects on the maternofetal unit of the rabbit model after substitution of the amniotic fluid with perfluorocarbons

Objectives: Exchanging amniotic fluid (AF) with perfluorocarbon (PFC) may serve as a medium for fetoscopic surgery. This study evaluates the distribution and physiologic effects of intraamniotic PFC as a medium for fetoscopy. Methods: Fetuses of 17 pregnant rabbits underwent either exchange of the AF with PFC, electrolyte solution (ES), or control. The quality of vision during fetoscopy was assessed in AF and PFC. After 6 h, we determined the distribution of PFC in the maternofetal unit. Results: Quality of vision during fetoscopy was better in PFC than with AF. There was no difference in fetal survival between the study groups. PFC was demonstrated on X-ray in the pharynx of 4 fetuses, and the esophagus in 1. Conclusions: PFC provided an ideal medium for fetoscopy without fetal compromise. Copyright (c) 2005 S. Karger AG, Basel

Creating a Long-Term Diabetic Rabbit Model

This study was to create a long-term rabbit model of diabetes mellitus for medical studies of up to one year or longer and to evaluate the effects of chronic hyperglycemia on damage of major organs. A single dose of alloxan monohydrate (100 mg/kg) was given intravenously to 20 young New Zealand White rabbits. Another 12 age-matched normal rabbits were used as controls. Hyperglycemia developed within 48 hours after treatment with alloxan. Insulin was given daily after diabetes developed. All animals gained some body weight, but the gain was much less than the age-matched nondiabetic rabbits. Hyperlipidemia, higher blood urea nitrogen and creatinine were found in the diabetic animals. Histologically, the pancreas showed marked beta cell damage. The kidneys showed significantly thickened afferent glomerular arterioles with narrowed lumens along with glomerular atrophy. Lipid accumulation in the cytoplasm of hepatocytes appeared as vacuoles. Full-thickness skin wound healing was delayed. In summary, with careful management, alloxan-induced diabetic rabbits can be maintained for one year or longer in reasonably good health for diabetic studies

Surgical technique for developing a rabbit model of congenital diaphragmatic hernia and tracheal occlusion

The surgical model of congenital diaphragmatic hernia (CDH) has been utilized in exploring treatments and innovative therapies, such as tracheal occlusion (TO). The rabbit is an excellent surgical model compared to others due to lower cost, ease of care, short gestational period, and large litter size. This model is also ideal in studying lung hypoplasia of CDH because rabbit lung development is most similar to humans as alveolarization begins prior to birth and continues post-natally. However, the surgical technique in creating a rabbit model of CDH is quite difficult and information is lacking on how to establish this model. Therefore, the aim of this paper is to describe: • Surgical technique in establishing a rabbit model of CDH and TO • Perioperative care for pregnant rabbit doe

Prosopis alba seed flour improves vascular function in a rabbit model of high fat diet-induced metabolic syndrome

Aims: Prosopis alba flour is a natural source of nutrient and phytochemicals with potential effects on cardiovascular risk factors. The aim of this work was to examine the effects of dietary supplementation with Prosopis alba seed flour (Pr-Feed) on a high fat diet (FD)-induced rabbit model of metabolic syndrome. Main methods: Rabbits were separated in four groups: fed regular diet (CD); CD supplemented with Pr-Feed; fed on 18 % FD; FD supplemented with Pr-Feed. All diets were administrated for 6 weeks. After the feeding period body weights, mean blood pressure, heart rate and visceral abdominal fat (VAF) were determined; glucose tolerance test (GTT) was performed; total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), fasting glucose (FG), aspartate amino transferase, alanine amino transferase, bilirubin and creatinine were measured in serum. Abdominal aorta was excised and vascular function was assessed by acetylcholine relaxation and contractile response to KCl, norepinephrine and angiotensin II. Key findings: Phytochemical analyses showed that the main compounds of Pr-Feed were apigenin C-glycosides. FD increased VAF, FG, TG, reduced HDL-cholesterol and induced abnormal GTT. Pr-Feed addition to FD did not modify these alterations. Aortic rings from rabbits fed on FD exhibited an impaired relaxation-response to acetylcholine and increased agonist vasoconstrictor responses. Pr Feed-supplemented FD improved the response to acetylcholine, and prevented the increase of the contractile response to KCl, norepinephrine and angiotensin II. Significance: Results suggest that dietary supplementation with Pr-Feed, rich in apigenin C-glycosides, has vascular protector properties and could be used to prevent vascular alterations characterizing the metabolic syndrome.Fil: Cattaneo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Roco, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Alarcón, Gabriela del Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Isla, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; ArgentinaFil: Jerez, Susana Josefina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentin