Luteolin induces cholangiocarcinoma cell apoptosis through the mitochondrial-dependent pathway mediated by reactive oxygen species

Recently, the toxic hydroxyl radical (·OH) has received wide interest in inducing cell apoptosis by increasing the intracellular reactive oxygen species (ROS) levels. Herein, a cationic polymer (MV-PAH) was rationally...

Download Full-text

CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22031106 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1106

Author(s):

Rayan Bou-Fakhredin ◽

Batoul Dia ◽

Hilda E. Ghadieh ◽

Stefano Rivella ◽

Maria Domenica Cappellini ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Mouse Model ◽

Cell Injury ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

Species Production ◽

Different Sources ◽

Dependent Pathway

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbbth3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbbth3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbbth3/+ mice through an NADPH-dependent pathway.

Download Full-text

Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.20:76-83 ◽

2021 ◽

Vol 20 (1) ◽

pp. 76-83

Author(s):

Chi-Sen Chang ◽

Yuh-Chiang Shen ◽

Chi-Wen Juan ◽

Chia-Lin Chang ◽

Po-Kai Lin

Keyword(s):

Reactive Oxygen Species ◽

Pc12 Cells ◽

Cell Apoptosis ◽

Active Component ◽

Caspase 3 ◽

Reactive Oxygen ◽

B Cell Lymphoma ◽

Oxygen Species ◽

Protein Levels ◽

Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

Download Full-text