Abstract
To develop pharmacological therapy for acute hepatic encephalopathy (AHE), understanding the molecular basis for cell injury is essential. Excitotoxic neural cell injury mediated by calpain as a post- receptor mechanism has been proposed as a player in neuronal injury in AHE. Concurrent assessment of Calpain and Caspase3 activities in the brain of AHE mice in acetaminophen- induced mourine model was performed. After induction of AHE by acetaminophen in mice, the model was confirmed by histopathological, biochemical and behavioural studies. The brains were removed, western blot analysis was done and the relative activity of calpain and caspase was estimated and compared to control group calpain but not caspase 3 activity was significantly increased in the AHE group compared to the control brains. Experimentally, this finding is the first to report. Increased calpain activity in liver has been previously reported. To translate both finding it can be suggested that calpain inhibition can be an investigational intervention in saving lives in AHE. To confirm the results, besides more advanced toxicodynamic studies on acetaminophen, the results should be confirmed in other models of AHE in future.
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Acknowledgements
This work is a part of thesis of PharmD approved by Shiraz Universiyy of Medical Sciences (project number 92-01-05-6478). The authors acknowledge Shiraz University of Medical Sciences for financial support. The study was a part of thesis to receive a degree of PharmD by B.Sh. (Grant number 709. The authors appreciate Dr. Maghboul and Dr. Azarpira for pathological evaluation of the livers. We truly appreciate Dr.Farjadian for her endless supports in the lab.
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M.F, B.Sh, A.J and O.K contributed to the Study concept and design. B.Sh, A.E and O.K had major roles in Acquisition of data either in animal experiments or in preparing the samples and performing the laboratory tasks. Data analysis and interpretation was performed by A.J, M.F. and A.E. Drafting of the manuscript was done by M.F, B.Sh, and A.J. All the authors contributed to Critical revision of the manuscript for important intellectual content. Statistical analyses was done by B.Sh and A.j. Administrative, technical, and material support was done by M.F, A.E, O.K and A.j. Study supervision was carried out by A.J and M.F.
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Shabrang, B., Jamshidzadeh, A., Farjam, M. et al. Concurrent assessment of calpain and caspase3 activities in brains of mice with acetaminophen-induced acute hepatic encephalopathy. Metab Brain Dis 32, 2139–2142 (2017). https://doi.org/10.1007/s11011-017-0096-z
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DOI: https://doi.org/10.1007/s11011-017-0096-z