Luteolin Ameliorates Methamphetamine-Induced Podocyte Pathology by Inhibiting Tau Phosphorylation in Mice

Abstract

Methamphetamine (METH) can cause kidney dysfunction. Luteolin is a flavonoid compound that can alleviate kidney dysfunction. We aimed to observe the renal-protective effect of luteolin on METH-induced nephropathies and to clarify the potential mechanism of action. The mice were treated with METH (1.0–20.0 mg/kg/d bodyweight) for 14 consecutive days. Morphological studies, renal function, and podocyte specific proteins were analyzed in the chronic METH model in vivo. Cultured podocytes were used to support the protective effects of luteolin on METH-induced podocyte injury. We observed increased levels of p-Tau and p-GSK3β and elevated glomerular pathology, renal dysfunction, renal fibrosis, foot process effacement, macrophage infiltration, and podocyte specific protein loss. Inhibition of GSK3β activation protected METH-induced kidney injury. Furthermore, luteolin could obliterate glomerular pathologies, inhibit podocyte protein loss, and stop p-Tau level increase. Luteolin could also abolish the METH-induced podocyte injury by inactivating GSK3β-p-Tau in cultured podocytes. These results indicate that luteolin might ameliorate methamphetamine-induced podocyte pathology through GSK3β-p-Tau axis.

Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus

“…In addition to neurotoxicity, METH can lead to hepatotoxicity, aortic aneurysm, renal dysfunction, etc. ( Ding et al, 2022 ; Luo et al, 2022 ; Zhang et al, 2022 ).…”