Luteolin alleviates inorganic mercury-induced kidney injury via activation of the AMPK/mTOR autophagy pathway.

Inorganic mercury is a ubiquitous toxic pollutant in the environment. Exposure to inorganic mercury can cause various poisonous effects, including kidney injury. However, no safe and effective treatment for kidney injury caused by inorganic mercury has been found and used. Luteolin (Lut) possesses various beneficial bioactivities. Here, our research aims to investigate the protective effect of Lut on renal injury induced by mercury chloride (HgCl2) and identify the underlying autophagy regulation mechanism. Twenty-eight 6-8 weeks old Wistar rats were randomly assigned to four groups: control, HgCl2, HgCl2 + Lut, and Lut. We performed the determination of oxidative stress and renal function indicators, histopathological analysis, the terminal deoxynucleotidyl transferase-mediated deoxyuracil nucleoside triphosphate nick-end labeling assay to detect apoptosis, western blot detection of autophagy-related protein levels, and atomic absorption method to detect mercury content. Our results showed that Lut ameliorated oxidative stress, apoptosis and restored the autophagy and renal function caused by HgCl2 in rats. Concretely, the level of nuclear factor E2-related factor, renal adenosine monophosphate-activated protein kinase (AMPK) expression, and autophagy regulation-related proteins levels were down-regulated, and the mammalian target of rapamycin (mTOR) expression was up-regulated by HgCl2 treatment. However, Lut treatment reversed the above changes. Notably, Lut reduced the accumulation of HgCl2 in the kidneys and promoted the excretion of HgCl2 through urine. Collectively, our results demonstrate that Lut can attenuate inorganic mercury-induced renal injury via activating the AMPK/mTOR autophagy pathway. Therefore, Lut may be a potential biological medicine to protect against renal damage induced by HgCl2.