Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan;85(1):36-44.

Evaluation of metallothionein and Ki-67 expression in chronic cholangiohepatitis in cats

Divya Jose  1 , Andrew L Allen  1 , Barry Blakley  1 , Ahmad Al-Dissi  1
Affiliations

Evaluation of metallothionein and Ki-67 expression in chronic cholangiohepatitis in cats

Divya Jose et al. Can J Vet Res. 2021 Jan.

Abstract
in English, French

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.

La cholangiohépatite chronique (CCH) est une affection pathologique courante chez les chats avec un pronostic réservé et une étiologie inconnue. Récemment, en médecine humaine, il y a eu un intérêt accru pour l’amélioration des mécanismes de défense hépatique en tant que stratégie de traitement efficace pour contrôler les maladies du foie qui ont un mauvais pronostic. La métallothionéine (MT) est une protéine omniprésente, qui a été largement étudiée pour son rôle dans la défense du foie par la détoxification des métaux lourds, la neutralisation des espèces réactives de l’oxygène et la régénération du foie. Dans cette étude, l’immunohistochimie a été utilisée pour évaluer le rôle de la MT dans la CCH et la régénération hépatocellulaire chez 34 chats diagnostiqués histologiquement avec cette condition en évaluant la corrélation entre l’expression hépatocellulaire de la MT et du Ki-67 (marqueur de la prolifération cellulaire) avec les paramètres histologiques de la CCH, comme l’inflammation, la fibrose et la prolifération des voies biliaires. L’analyse statistique a été réalisée à l’aide du test de corrélation de rang de Spearman. Une corrélation positive significative a été observée entre l’inflammation et le nombre d’hépatocytes MT-positifs (r = 0,36, P = 0,03) et l’intensité de marquage MT (r = 0,37, P = 0,03). Dans 16 des 34 cas (47 %), l’intensité du marquage MT était prononcée vers la zone centrolobulaire et très faible ou absente vers la zone porte. Les résultats suggèrent que la MT est induite dans le foie pendant les états inflammatoires chroniques, ce qui pourrait être supposé comme un mécanisme de défense de l’hôte pour protéger le foie contre les lésions hépatiques induites par l’inflammation. Les interventions thérapeutiques utilisant la MT peuvent donc avoir un effet positif sur les chats atteints de cholangiohépatite chronique.(Traduit par Docteur Serge Messier).

PubMed Disclaimer

Figures

Figure 1
Figure 1
A — Photomicrograph of a liver from a cat affected by chronic cholangiohepatitis (10×). Note the centrilobular zones (arrowhead) devoid of inflammatory cells and the portal zones surrounded by abundant infiltration of lymphocytes and plasma cells, together with fibrosis and bile duct proliferation (arrows). B — Portal zones contain multiple bile ducts surrounded by abundant infiltration of lymphocytes and plasma cells. Case no. 2. H & E staining.
Figure 2
Figure 2
Photomicrographs of the liver from cats affected by chronic cholangiohepatitis, stained with Masson’s Trichrome (10×). A — Score ‘1,’ presence of fibrosis around portal tracts only. Case no. 11. B — Score ‘2,’ presence of nonbridging fibrosis extending beyond portal or centrilobular areas into the hepatic parenchyma. Case no. 20. C — Score ‘3,’ presence of bridging fibrosis. Case no. 32.
Figure 3
Figure 3
Photomicrograph of a liver from a cat affected by chronic cholangiohepatitis, immunohistochemically stained for MT expression (40×). Arrowheads indicate hepatocytes with positive MT staining. Note diffuse dark brown cytoplasmic staining and variable nuclear staining in MT positive cells. Labelling intensity score ‘2.’ Case no. 24. DAB staining & hematoxylin counterstaining.
Figure 4
Figure 4
Photomicrograph of a normal liver from a cat, immunohistochemically stained for MT expression (40×). None of the cells stain positive for MT. Labelling intensity score ‘0.’ Case no. 37. DAB staining & hematoxylin counterstaining.
Figure 5
Figure 5
Photomicrograph of a liver from a cat affected by chronic cholangiohepatitis, immunohistochemically stained for MT expression (40×). All the cells in the section express MT. Labelling intensity score ‘3.’ Case no. 1. DAB staining & hematoxylin counterstaining.
Figure 6
Figure 6
Photomicrograph of a liver from a cat affected by chronic cholangiohepatitis, immunohistochemically stained for Ki-67 expression (40×). Arrow points to the dark brown intranuclear staining in a hepatocyte with positive Ki-67 expression. Case no. 12. DAB staining & hematoxylin counterstaining.
Figure 7
Figure 7
Photomicrograph of a liver from a cat affected by chronic cholangiohepatitis, immunohistochemically stained for MT expression (10×). Note the labelling intensity is strongest in cells near the centrilobular zone and weak in cells near the portal zone. A — Case no. 9. B — Case no. 11. DAB staining & hematoxylin counterstaining.
See this image and copyright information in PMC

References

    1. Callahan Clark JE, Haddad JL, Brown DC, Morgan MJ, Van Winkle TJ, Rondeau MP. Feline cholangitis: A necropsy study of 44 cats (1986–2008) J Feline Med Surg. 2011;13:570–576. - PMC - PubMed
    1. Day DG. Feline cholangiohepatitis complex. Vet Clin North Am Small Anim Pract. 1995;25:375–385. - PubMed
    1. Brain PH, Barrs VR, Martin P, Baral R, White JD, Beatty JA. Feline cholecystitis and acute neutrophilic cholangitis: Clinical findings, bacterial isolates and response to treatment in six cases. J Feline Med Surg. 2006;8:91–103. - PMC - PubMed
    1. Gagne JM, Weiss DJ, Armstrong PJ. Histopathologic evaluation of feline inflammatory liver disease. Vet Pathol. 1996;33:521–526. - PubMed
    1. Solís Herruzo JA, Solís-Muñoz P, Muñoz-Yagüe T, García-Ruiz I. Molecular targets in the design of antifibrotic therapy in chronic liver disease. Rev Esp Enfermedades Dig. 2011;103:310–323. - PubMed

LinkOut - more resources