Morin attenuates arsenic-induced toxicity in 3T3 embryonic fibroblast cells by suppressing oxidative stress, inflammation, and apoptosis: In vitro and silico evaluations.
Velid UnsalMustafa CicekNecmettin AktepeErkan OnerPublished in: Toxicology research (2024)
This study aims to investigate the curative effects of Morin, a flavonoid, against arsenic toxicity in 3T3 embryonic fibroblast cells and its effect on the molecular mechanisms of cells. The cytotoxicity and viability of the cells were measured by MTT and LDH tests. Arsenic (0.74 μM) was used to trigger toxicity and Morin (50 μM) was used for treatment. The levels of oxidative stress biomarkers and the activities of antioxidant enzymes were measured by spectrophotometric method, and inflammatory markers were measured by ELISA method. While mRNA expression levels of Bax, Bcl-2 levels, and Caspase-3 activity were measured by qRT-PCR technique, TUNEL staining was performed to detect DNA breaks and DAPI staining to visualize nuclear changes. Protein structures were retrieved from the protein data bank. OpenBabel and Autodock programs were used for the molecular docking study. Morin rescued the 3T3 embryonic fibroblast cells exposed to arsenic. However, Arsenic decreased the activities of antioxidant enzymes in cells and significantly increased oxidative stress, inflammation, and apoptosis. Morin treatment reduced oxidative damage and TNF-α and IL-1β levels. Arsenic-induced Caspase-3 mRNA expression level and Bax protein mRNA expression level were significantly increased, while Bcl-2 mRNA expression level was significantly decreased. While Caspase-3 mRNA expression level and Bax protein mRNA expression level decreased with morin treatment, Bcl-2 mRNA expression level increased significantly. Molecular docking study results showed good binding affinity of morin in SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α, and IL-1β structures. Morin showed antioxidant, anti-inflammatory, and anti-apoptotic effects against Arsenic-induced cellular toxicity.
Keyphrases
- induced apoptosis
- oxidative stress
- diabetic rats
- endoplasmic reticulum stress
- cell cycle arrest
- molecular docking
- cell death
- signaling pathway
- ischemia reperfusion injury
- dna damage
- drinking water
- heavy metals
- anti inflammatory
- endothelial cells
- risk assessment
- pi k akt
- high glucose
- machine learning
- mass spectrometry
- drug induced
- high resolution
- dna binding
- combination therapy
- artificial intelligence
- cell proliferation
- flow cytometry
- liquid chromatography