IJBST 2019 Volume 12 Issue 3

Rohini Keshava, Vikas Vazhayil, Rohan Mitra, Indira Devi Bhagavatula, & Rajalakshmi Gope. (2019). AlCl3 causes Fas/Fas-L mediated cell death in the cortex and hippocampus of mouse brain. International Journal of Biosciences and Technology (IJBST) ISSN: 0974-3987, 12(3), 21–35. http://doi.org/10.5281/zenodo.3369193

AlCl3 causes Fas/Fas-L mediated cell death in the cortex and hippocampus of mouse brain

Rohini Keshava1, Vikas Vazhayil2, Rohan Mitra3, Indira Devi Bhagavatula4 and Rajalakshmi Gope5

1 Department of Biotechnology, Faculty of Life and Allied Health Sciences, Bangalore 560054, India.

2,4 Department of Neurosurgery, NIMHANS, Bangalore 560029, India.

3 Medical Writer, Sanofi, Mumbai 400072, India.

5 Department of Human Genetics, NIMHANS, Bangalore 560029, India.

rohinikeshavaofficial@gmail.com; vikas.drv@gmail.com; mitrohan@gmail.com; bidevidr@gmail.com; rlgope@gmail.com

ABSTRACT

In this study effect of sustained toxicity of low dose of aluminum trichloride (AlCl3, Anhydrous) in mouse brain and liver was evaluated. Six weeks old Swiss albino mice were given orally 2 mg AlCl3/ kg body weight / per day for three consecutive weeks. Three weeks after last feeding the brain and liver tissues were examined for histopathological changes which revealed Al toxicity related changes. Oral administration AlCl3 caused a slight decrease in the whole-body weight and a significant decrease in the weight of liver and brain tissues. In addition, AlCl3 ingestion resulted in increased level of total protein in the liver but decreased the same in the brain tissue in the experimental mice. AlCl3 feeding also caused DNA laddering that is characteristics of apoptotic cell death in the liver and brain tissues. Moreover, AlCl3 feeding lead to decreased level of anti-apoptotic Bcl2 and PI3K proteins, and increased levels of p53 as well as pro-apoptotic phospho c-Jun N-terminal kinase (pJNK), Bax, Caspase 3, p21 and Fas proteins in the cortex and in the hippocampus regions. Trace level of Fas protein was present in the cortex and hippocampus regions of the control brain which increased to 2 to 3-fold upon AlCl3 feeding. Higher level of Fas ligand was present in the cortex and hippocampus regions of the control and it remained unchanged with AlCl3 ingestion. Our data shows that the observed cell death caused by AlCl3 in the cortex and hippocampus region of mouse brain could be Fas mediated.

Running title: Aluminium chloride causes Fas mediated cell death

Key words: AlCl3, apoptosis, Bcl2: Bax ratio, cell death/survival, Fas/Fas-L, p53