How aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale

Abstract

Metal pollutants are a global health risk due to their ability to contribute to a variety of diseases. Aluminum (Al), a ubiquitous environmental contaminant is implicated in anemia, osteomalacia, hepatic disorder, and neurological disorder. In this review, we outline how this intracellular generator of reactive oxygen species (ROS) triggers a metabolic shift towards lipogenesis in astrocytes and hepatocytes. This Al-evoked phenomenon is coupled to diminished mitochondrial activity, anerobiosis, and the channeling of α-ketoacids towards anti-oxidant defense. The resulting metabolic reconfiguration leads to fat accumulation and a reduction in ATP synthesis, characteristics that are common to numerous medical disorders. Hence, the ability of Al toxicity to create an oxidative environment promotes dysfunctional metabolic processes in astrocytes and hepatocytes. These molecular events triggered by Al-induced ROS production are the potential mediators of brain and liver disorders.

Aluminium Involvement in Neurotoxicity

“…They represent a global health risk because of their ability to contribute to a variety of diseases. In this context, Al (which is a highly reactive element and ubiquitous environmental contaminant) has been associated with some diseases [1]. In fact, osteomalacia is a skeletal disease related to Al toxic effects, such as phosphate deficiency, Ca-uptake impairment, and dysfunctional osteoblast proliferation [19].…”

“…Al is a highly abundant and ubiquitously distributed as environmental and industrial toxicant and is also contained in many food products, being involved in skeletal, haematological, and neurological diseases [1]. Al toxicity is caused by disruption of homeostasis of metals such as magnesium, calcium, and iron (Fe): in fact, Al mimics these metals in their biological functions and triggers many biochemical alterations [2].…”

Bioactivity of Mineral Trioxide Aggregate and Mechanism of Action

“…These results have led to the preparation of experiment bioactive tricalcium silicate [30,48] and dicalcium silicate [25] cements for endodontic applications. The use of these experimental calcium silicate cements should alleviate potential concerns regarding aluminium-induced neurotoxicity [69,141,171] that may arise with the clinical use of clinker-derived tricalcium aluminate-containing hydraulic calcium (alumino)silicate cements.…”

Brain metabolism and Alzheimer's disease: The prospect of a metabolite-based therapy

“…The majority of the energy of the brain (~ 90%) is generated in the mitochondria via oxidative phosphorylation. The production of adenosine triphosphate (ATP), the universal energy currency, necessitates the formation of reactive oxygen species (ROS) that are nullified with the aid of a plethora of antioxidative tools such as superoxide dismutase (23,24). Dysfunctional mitochondrial activity can also be a cause of AD (25).…”

“…An elevated amount of both pyruvate and α-ketoglutarate has been reported in astrocytes subjected to hydrogen peroxide (H2O2) and Al respectively (24,30). A switch to ICDH-NADP dependent metabolism affords NADPH and αKG.…”