Sodium Butyrate Ameliorates Fluorosis-Induced Neurotoxicity by Regulating Hippocampal Glycolysis In Vivo

Abstract

Fluorosis can induce neurotoxicity. Sodium butyrate (SB), a histone deacetylase inhibitor, has important research potential in correcting glucose metabolism disorders and is widely used in a variety of neurological diseases and metabolic diseases, but it is not yet known whether it plays a role in combating uoride-induced neurotoxicity. This study aims to evaluate the effect of SB on uoride neurotoxicity and the possible associated mechanisms. The results of HE staining and Morris water maze showed that in mice exposed to 100 mg/L uoride for three months, the hippocampal cells arranged in loosely with large cell gaps and diminished in number. In addition, 1000 mg/kg/day SB treatment improved uorideinduced neuronal cell damage and spatial learning memory impairment. Western blotting showed that the abundance of malate dehydrogenase 2 (MDH2) and pyruvate dehydrogenase (PDH) in the hippocampus of mice increased after uorosis, while the abundance of pyruvate kinase M (PKM), lactate dehydrogenase (LDH) and hexokinase (HK) decreased. SB treatment reversed the decreased glycolysis in the hippocampus of uorosis mice. We suspected that the PI3K/AKT/HIF-1α pathway may be involved in mediating the protective effects of SB against uorosis invasion in the hippocampus. These results suggested that SB could ameliorate uorosis-induced neurotoxicity, which might be linked with its function in regulating glycolysis as well as inhibition of the PI3K/AKT/HIF-1α pathway.

Uncovering novel therapeutic targets in glucose, nucleotides and lipids metabolism during cancer and neurological diseases

“… 79 Fluorosis-induced neurotoxicity links to the PI3K/AKT/HIF-1α pathway and ameliorates by Sodium Butyrate Regulating Hippocampal Glycolysis InVivo. 80 The microbe-gut-brain axis shows neurotoxicity during exposure to imidacloprid. 81 Glycogen mediates metabolic switching in ischemic astrocytes during neurotoxicity.…”

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

“…The results of the current study reveal that an overdose of fluoride induces liver damage. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are two important intracellular biomarkers for assessing liver function [ 29 ]. The serum levels of ALT and AST increase during hepatocyte injury due to the increased permeability of the cell membranes [ 33 , 34 ].…”

“…The wax blocks were placed in a temperature box at 60 °C for 2 h and dried, the paraffin sections were immersed in hematoxylin for 5 min followed by eosin for 2 min, and the slides were dehydrated and sealed with a neutral resin. A Leica DM1000 microscope (Leica, Heidelberg, Germany) was used to observe the histopathological changes [ 29 ].…”