Neurodegenerative and Hepatorenal Disorders Induced Via Aluminum Chloride in Murine System: Impact of β-Secretase, MAPK, and KIM

Aluminum chloride (AlCl3) is commonly used in daily life; meanwhile, it is the potential etiology of various neurodegenerative as well as hepatorenal diseases. Therefore, the present study was carried out to investigate the correlation between AlCl3-induced biochemical alterations and the toxicity induced in various organs such as the brain, liver, and kidney. Male mice received AlCl3 in an oral dose of 50 mg kg(-1) in addition to (50 mg) in drinking water for 2 weeks. Two weeks post-AlCl3 intoxication, the brain, liver, and kidney biochemical indices were assessed via molecular and western blot analysis. The results are as follows: AlCl3 intoxication induced a significant elevation in serum malondialdehyde in addition to a significant reduction in serum glutathione (GSH) and superoxide dismutase (SOD) levels. Brain beta-secretase (tubulin-binding protein) and tau proteins which are responsible for the synthesis of beta-amyloid protein that may interfere with neuronal communication in Alzheimer's disease (AD) were also upregulated; regarding hepatic function, AlCl3 elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Moreover, it upregulated hepatic mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) protein expressions as well as renal kidney-inducible molecule-1 (KIM-1) which indicated the deleterious effect of AlCl3 on these organs. These results were confirmed by histopathological investigations. So, we hypothesize that acute AlCl3 administration is responsible for oxidative cell damage that interferes with brain function inducing beta-amyloid accumulation, Alzheimer's disease, and neurodegenerative damage as well as hepatorenal injuries.

Automated summary

This study revealed significant biochemical alterations induced by AlCl3 in the brain, liver, and kidney, including oxidative damage and changes in protein expressions, which may contribute to the development of various diseases.