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

Jiuyang Ding; Yuanhe Wang; Zhuo Wang; Shanshan Hu; Zhu Li; Cuiyun Le; Jian Huang; Xiang Xu; Jiang Huang; Pingming Qiu

doi:10.1155/2022/5909926

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

Evid Based Complement Alternat Med. 2022 Mar 24:2022:5909926. doi: 10.1155/2022/5909926. eCollection 2022.

Authors

Jiuyang Ding^{1

2}, Yuanhe Wang¹, Zhuo Wang³, Shanshan Hu⁴, Zhu Li¹, Cuiyun Le¹, Jian Huang², Xiang Xu⁵, Jiang Huang¹, Pingming Qiu²

Affiliations

¹ Department of Forensic Medicine, Guizhou Medical University, Guiyang 550004, Guizhou, China.
² School of Forensic Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
³ Department of Infertility and Sexual Medicine, The Third Affiliated hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China.
⁴ Good Clinical Practice Center, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China.
⁵ School of Forensic Medicine, Wannan Medical College, Wuhu 241000, Anhui, China.

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.