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Luteolin inhibits multi-heavy metal mixture-induced HL7702 cell apoptosis through downregulation of ROS-activated mitochondrial pathway.

Abstract：

:With the rapid economic development in recent years, China is facing a great challenge due to heavy metal pollution. The heavy metals may enter the human body through ingestion of aqua products to cause great health risks. In the present study, the inhibitory effects of luteolin on the combined toxicity of multi-heavy metals (including zinc, manganese, lead, copper, cadmium, mercury, chromium and nickel) were investigated in HL7702 hepatocyte cells. An MTT assay demonstrated that 20 µM luteolin significantly alleviated the multi-heavy metal mixture-induced cell death and morphological changes. Furthermore, 20 µM luteolin significantly inhibited multi-heavy metal mixture-induced reactive oxygen species (ROS) generation, lipid peroxidation (malondialdehyde content) and caused a decrease in adenosine triphosphate levels in HL7702 cells. A JC-1 staining assay indicated that 20 µM luteolin inhibited the mitochondrial membrane potential-reducing effect of the multi-heavy metal mixture. Apoptotic assays revealed that the multi-heavy metal mixture induced HL7702 cell apoptosis in a dose-dependent manner, which was significantly inhibited by 20 µM luteolin. Western blot analysis indicated that addition of luteolin to the multi‑heavy metal mixture significantly alleviated cytochrome c release from the mitochondria into the cytosol. In addition, 20 µM luteolin had a significant inhibitory effect on multi-heavy metal mixture-induced cleavage of caspase-9, caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein. Immunofluorescence staining demonstrated that addition of luteolin significantly alleviated caspase-3 cleavage induced by the multi-heavy metal mixture. The present results suggested luteolin exerts its inhibitory effects of on multi-heavy metal mixture induced cell apoptosis through downregulation of the ROS-activated mitochondrial pathway.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Wang Y,Su H,Song X,Fiati Kenston SS,Zhao J,Gu Y

doi

10.3892/ijmm.2017.3219

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

233-241

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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Luteolin inhibits multi-heavy metal mixture-induced HL7702 cell apoptosis through downregulation of ROS-activated mitochondrial pathway.