Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt

Abstract

Given the observable toxicity of lithium carbonate, neuropharmacology requires effective and non-toxic lithium salts. In particular, these salts can be employed as neuroprotective agents since lithium ions demonstrate neuroprotective properties through inhibition of glycogen synthetase kinase-3β and other target proteins, increasing concentrations of endogenous neurotrofic factors. The results of theoretical and experimental studies of organic lithium salts presented here indicate their potential as neuroprotectors. Chemoreactomic modeling of lithium salts made it possible to select lithium ascorbate as a suitable candidate for further research. A neurocytological study on cerebellar granular neurons in culture under conditions of moderate glutamate stress showed that lithium ascorbate was more effective in supporting neuronal survival than chloride or carbonate, i.e., inorganic lithium salts. Biodistribution studies indicated accumulation of lithium ions in a sort of “depot”, potentially consisting of the brain, aorta, and femur. Lithium ascorbate is characterized by extremely low acute and chronic toxicity (LD50 > 5000 mg/kg) and also shows a moderate antitumor effect when used in doses studied (5 or 10 mg/kg). Studies on the model of alcohol intoxication in rats have shown that intake of lithium ascorbate in doses either 5, 10 or 30 mg/kg did not only reduced brain damage due to ischemia, but also improved the preservation of myelin sheaths of neurons.

Keywords

• lithium therapy
• neurocytology
• toxicology
• neuroprotection
• chemoinformatics
• big data