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Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells
M A Siddiqui1, J Ahmad, N N Farshori
1Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia, maqsoodahmads@gmail.com.
Abstract:
Rotenone, a commonly used pesticide, is well documented to induce selective degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced neurodegenration has been primarily suggested through mitochondria-mediated apoptosis and reactive oxygen species (ROS) generation. But the status of rotenone induced changes in liver, the major metabolic site is poorly investigated. Thus, the present investigation was aimed to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2 receiving experimental exposure of rotenone (12.5-250 μM) for 24 h. Rotenone depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic responses were in concurrence with the markers associated with oxidative stress such as an increase in ROS generation and lipid peroxidation as well as a decrease in the glutathione, catalase, and superoxide dismutase levels. The decrease in mitochondrial membrane potential also confirms the impaired mitochondrial activity. The events of cytotoxicity and oxidative stress were found to be associated with up-regulation in the expressions (mRNA and protein) of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone-induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3.
Insights
Rotenone pesticide exposure causes liver cell damage by increasing oxidative stress and triggering apoptosis. This study reveals rotenone
Area of Science:
- Hepatotoxicity and cellular toxicology
- Environmental toxicology
- Biochemistry and molecular biology
Background:
- Rotenone, a pesticide, is known to cause neurodegeneration via mitochondrial dysfunction and reactive oxygen species (ROS) generation.
- The effects of rotenone on liver cells, a key metabolic organ, remain under-investigated.
Purpose of the Study:
- To investigate rotenone-induced oxidative stress, cytotoxicity, and apoptotic cell death in human liver cells (HepG2).
- To elucidate the molecular mechanisms underlying rotenone's hepatotoxic effects.
Main Methods:
- Human liver cells (HepG2) were exposed to varying concentrations of rotenone (12.5–250 μM) for 24 hours.
- Assessed cytotoxicity, ROS generation, lipid peroxidation, and antioxidant levels (glutathione, catalase, superoxide dismutase).
- Evaluated mitochondrial membrane potential and the expression of apoptosis-related proteins (p53, Bax, Bcl-2, caspase-3).
Main Results:
- Rotenone induced a dose-dependent cytotoxic response in HepG2 cells.
- Increased ROS generation and lipid peroxidation, alongside decreased antioxidant levels, indicated significant oxidative stress.
- Rotenone exposure led to decreased mitochondrial membrane potential and altered expression of apoptosis markers, favoring cell death.
Conclusions:
- Rotenone induces cytotoxicity and apoptosis in human liver cells (HepG2) through ROS-mediated oxidative stress.
- Mitochondrial dysfunction and the p53/Bax/Bcl-2/caspase-3 pathway are critically involved in rotenone-induced hepatotoxicity.
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