Chronic cholangiohepatitis (CCH) is a common pathological condition in cats with a guarded prognosis and unknown etiology. Recently, in human medicine, there has been increased interest in enhancing liver defense mechanisms as an effective treatment strategy to control liver diseases that have a poor prognosis. Metallothionein (MT) is a ubiquitous protein, which has been widely researched for its role in liver defense through heavy metal detoxification, neutralization of reactive oxygen species, and liver regeneration. In this study, immunohistochemistry was used to evaluate the role of MT in CCH and hepatocellular regeneration in 34 cats histologically diagnosed with this condition by assessing the correlation between hepatocellular MT and Ki-67 (marker for cellular proliferation) expression with histological parameters of CCH, such as inflammation, fibrosis, and bile duct proliferation. Statistical analysis was performed using the Spearman-rank correlation test. A significant positive correlation was observed between inflammation and the number of MT-positive hepatocytes (r = 0.36, P = 0.03) and MT labelling intensity (r = 0.37, P = 0.03). In 16 of 34 cases (47%) MT labelling intensity was noted to be pronounced towards the centrilobular zone and very weak or absent towards the portal zone. The results suggest that MT is induced in the liver during chronic inflammatory conditions, which could be speculated as a host defensive mechanism to protect the liver from inflammation-mediated liver injury. Therapeutic interventions utilizing MT, therefore, may have a positive effect on cats with chronic cholangiohepatitis.

Objective: To characterize mucosal gene expression in dogs with chronic enteropathy (CE). Animals: 18 dogs with CE and 6 healthy control dogs. Procedures: Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed. Results: 1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis. Conclusions and Clinical Relevance: Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity. Impact for Human Medicine: Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.

This study was conducted to investigate the effects of the sources and levels of dietary copper supplementation on broiler chickens. A 37-day feeding trial was accomplished using 192 one-day-old unsexed Arbor Acres broiler chicks which were randomly allocated into four groups with different strategies of copper supplementation. The first group was the negative control and fed on diets containing copper-free mineral-vitamin broiler premix. Diets of the second group were supplemented with copper sulfate (Cu2SO4) at the level of 7.5 mg/kg. The third and fourth groups were fed on diets supplemented with copper nanoparticles (Cu-NPs) at the levels of 7.5 mg/kg and 3.75 mg/kg, respectively. Growth performance, carcass characteristics, copper concentrations, serum antioxidant bio-markers and mRNA of metallothionein and ceruloplasmin were evaluated. Results of growth performance showed that Cu-NPs significantly (P ≤ 0.05) increased body weight gain and feed utilization compared to an equal quantity of Cu2SO4. No adverse effect on growth performance occurred when Cu-NPs were supplemented at half of the level of Cu2SO4. Dressing and thigh yields were significantly (P ≤ 0.05) increased in birds in the fourth group. Total antioxidant capacity, malondialdehyde level and transcription of ceruloplasmin were not significantly affected by the tested copper sources or levels. The superoxide dismutase enzyme activity and transcription of metallothionein were significantly (P ≤ 0.05) increased by the replacement of Cu2SO4 with the same quantity of Cu-NPs. Our findings suggested that Cu-NPs could be a superior dietary supplement of copper in broiler chickens’ diets over Cu2SO4, with possibility of quantity reduction.