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Pathology Update 2025
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Iron and the induction of ferroptosis in an animal model of type 1 hereditary haemochromatosis

Roche Scientific E Poster Display

Roche Scientific E-Poster Display

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Genetic Pathology

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Abstracts/Presentation Description

Moeza Arona Merchant1,2, Afolabi Akanbi1,2, Kim Bridle1,2, Greg Miller3, Darrell Crawford2
1Faculty of Medicine, The University of Queensland; 2Gallipoli Medical Research; 3Envoi Specialist Pathologists, Brisbane

 
Iron toxicity is associated with acute liver injury and chronic liver pathologies, such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis1,2. In hereditary haemochromatosis (HH), iron deposition is genetically driven and can potentiate the injury caused by other co-existent liver diseases 1,2. Ferroptosis is an iron-dependent cellular death pathway and has been implicated in various types of liver disease 3. This study examined the ferroptosis pathway caused by oxidative stress and secondary iron exposure in mice with type 1 HH. Forty Hfe-/- mice were assigned to four different groups according to diet and iron consumption (high-calorie vs low-calorie and standard iron vs low iron). Real-time PCR was performed on ferroptosis-associated genes and standardized to housekeeping genes. Haematoxylin-eosin (H & E) and Perls’ stains were applied to the liver samples to demonstrate the grade of iron and liver steatosis in the different mice groups. A low-iron diet led to a downregulation of ferroptosis-associated genes and reduced Perls’ staining compared to diets with standard iron levels. Steatosis was also reduced in mice on a low iron/high calorie diet. These findings indicate that iron modulation and the ferroptosis pathway could become a target for therapeutic interventions in chronic liver pathologies, such as NAFLD. 

References:

1.      Allameh A, Niayesh-Mehr R, Aliarab A, Sebastiani G, Pantopoulos K. Oxidative stress in liver pathophysiology and disease. Antioxidants. 2023 Aug 22;12(9):1653.
2.      Crawford DH, Ramm GA, Bridle KR, Nicoll AJ, Delatycki MB, Olynyk JK. Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver. Hepatology International. 2023 Jun;17(3):522-41.
3.      Liu P, Anandhan A, Chen J, Shakya A, Dodson M, Ooi A, Chapman E, White E, Garcia JG, Zhang DD. Decreased autophagosome biogenesis, reduced NRF2, and enhanced ferroptotic cell death are underlying molecular mechanisms of non-alcoholic fatty liver disease. Redox Biology. 2023 Feb 1;59:102570.

Presenting Author Statement:
I am the primary author of this abstract and conducted the experiments under the guidance of my co-authors and supervisors. 
AI was not used in the writing process.

Speaker/Presenting Authors

Authors

Submitting/Presenting Authors

Ms Moeza Arona Merchant - University of Queensland (Queensland, Australia )

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