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.

Metabolic Responses to Manganese Toxicity in Soybean Roots and Leaves

“…Furthermore, seedling roots of L. luteus preprocessing with total flavone extracted from Pb-treated cotyledons exhibit strengthened toleration to heavy metal stress [40]. Luteolin, a common flavonoid, has an inhibitory effect on the toxicity induced by heavy metals [41]. For example, luteolin regulates the redox imbalance, preserves mitochondrial function, and depresses caspase-family-associated apoptosis induced by copper (Cu) [42].…”

Luteolin Alleviates Cadmium-Induced Kidney Injury by Inhibiting Oxidative DNA Damage and Repairing Autophagic Flux Blockade in Chickens

“…Many studies have found that Lut effectively ameliorates heavy metal-induced pathological lesions in various organs by enhancing antioxidant enzyme activities and reversing mitochondrial dysfunction [27][28][29]. Moreover, Lut inhibits PARP-1 activation and apoptosis induced by a mixture of heavy metals via reducing reactive oxide species (ROS) levels [30]. Recent studies have reported that the hepatorenal protective effects of Lut involve the activation of SIRT1 and the repair of impaired autophagic flux [31][32][33].…”

Inhibition of the BNIP3/NIX‐dependent mitophagy aggravates copper‐induced mitochondrial dysfunction in duck renal tubular epithelial cells

“…These processes lead to the accumulation of toxic metabolites in cells. Excessive heavy metals invade the human body, leading to the decrease of mitochondrial number and mitochondrial respiratory chain enzyme activity, eventually the mitochondrial respiratory function 12 . More disadvantageous is that dysfunctional mitochondria can increase the production and release of reactive oxygen species, further aggravating mitochondrial damage 13 .…”

“…Excessive heavy metals invade the human body, leading to the decrease of mitochondrial number and mitochondrial respiratory chain enzyme activity, eventually the mitochondrial respiratory function. 12 More disadvantageous is that dysfunctional mitochondria can increase the production and release of reactive oxygen species, further aggravating mitochondrial damage. 13 Therefore, mitochondrial health is particularly crucial for maintaining the normal physiological functions of the kidney.…”