Pathobiological Mechanisms of Endothelial Dysfunction Induced by tert -Butyl Hydroperoxide via Apoptosis, Necrosis and Senescence in a Rat Model

International Journal of Medical Sciences
Yueh-Chiao YehHui-Chin Lai

Abstract

Background: Endothelial dysfunction is one of the underlying causes for vascular diseases. tert-Butyl hydroperoxide (t-BHP), a short-chain lipid hydroperoxide analog, has been reported to cause adverse effects in different systems. However, the adverse actions of t-BHP on inducing endothelial dysfunction are unclear and remain under investigation. Aim of the present study was to identify the pathobiological mechanisms of t-BHP in rat aortic endothelial cells and thoracic aorta. Methods: Primary cultured cells were treated with vehicle or t-BHP (50, 100, 250, 500, and 1,000 μM). Cells were harvested and specific analyses regarding cellular apoptosis, necrosis, and senescence were conducted. Additionally, t-BHP (0.1, 0.2, and 0.4 mmol/kg body weight) or vehicle were administered to male rats (the young group at 6 weeks of age and the mature adult group at 24 weeks of age) daily through intraperitoneal injections. At 10 days after the first drug treatment apoptotic endothelial toxicity was evaluated by biochemical, histological, and immunofluorescent staining analyses. Results: Dose-dependent effects of t-BHP were observed for the reduction of cell viability, deterioration of cell toxicity, initiation of cell cycle arrest, and tri...Continue Reading

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
Assay

Software Mentioned

CellQuest TM Pro
Advanced Spot RT
ScienceLab 2001 ImageGauge

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis