Related Experiment Video
Updated: May 30, 2026
A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice
Published on: April 16, 2018
Exogenous melatonin modulates apoptosis in the mouse brain induced by high-LET carbon ion irradiation
Yang Liu1, Luwei Zhang, Hong Zhang
1Department of Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
Abstract:
The aim of this study was to investigate whether melatonin, a free radical scavenger and a general antioxidant, regulates the brain cell apoptosis caused by carbon ions in mice at the level of signal transduction pathway. Young Kun-Ming mice were divided into five groups: control group, irradiation group and three melatonin (1, 5, and 10 mg/kg daily for 5 days i.p.) plus irradiation-treated groups. An acute study was carried out to determine oxidative status, apoptotic cells, and mitochondrial membrane potential (ΔΨm) as well as pro- and anti-apoptotic protein levels in a mouse brain 12 hr after irradiation with a single dose of 4 Gy. In irradiated mice, a significant rise in oxidative stress and apoptosis (TUNEL positive) was accompanied by activated expression of Bax, cytochrome c, caspase-3, and decreased ΔΨm level. Melatonin supplementation was better able to reduce irradiation-induced oxidative damage marked by carbonyl or malondialdehyde content, and stimulate the antioxidant enzyme activities (superoxide dismutase and catalase) together with total antioxidant capacity. Moreover, administration with melatonin pronouncedly elevated the expression of Nrf2 which regulates redox balance and stress. Furthermore, melatonin treatment mitigated apoptotic rate, maintained ΔΨm, diminished cytochrome c release from mitochondria, down-regulated Bax/Bcl-2 ratio and caspase-3 levels, and consequently inhibited the important steps of irradiation-induced activation of mitochondrial pathway of apoptosis. Thus, we propose that the anti-apoptotic action with the alterations in apoptosis regulator provided by melatonin may be responsible at least in part for its antioxidant effect by the abolishing of carbon ion-induced oxidative stress along with increasing Nrf2 expression and antioxidant enzyme activity.
Insights
Melatonin, a potent antioxidant, protects brain cells from carbon ion radiation damage by reducing oxidative stress and inhibiting apoptosis. This study shows melatonin enhances antioxidant defenses and blocks key cell death pathways.
Area of Science:
- Neuroscience
- Radiology
- Biochemistry
Background:
- Carbon ion irradiation induces oxidative stress and apoptosis in brain cells.
- Melatonin is a known free radical scavenger with antioxidant properties.
Purpose of the Study:
- To investigate melatonin's role in regulating carbon ion-induced brain cell apoptosis.
- To explore the effects of melatonin on the signal transduction pathway involved in apoptosis.
Main Methods:
- Mice were divided into control, irradiation, and melatonin-treated groups.
- Oxidative status, apoptosis, mitochondrial membrane potential (ΔΨm), and protein levels were assessed 12 hours post-irradiation.
- Melatonin was administered intraperitoneally at doses of 1, 5, and 10 mg/kg.
Main Results:
- Irradiation increased oxidative stress, apoptosis, and activated pro-apoptotic proteins (Bax, cytochrome c, caspase-3), while decreasing ΔΨm.
- Melatonin reduced oxidative damage, enhanced antioxidant enzyme activity (superoxide dismutase, catalase), and increased total antioxidant capacity.
- Melatonin upregulated Nrf2 expression, maintained ΔΨm, reduced cytochrome c release, and down-regulated the Bax/Bcl-2 ratio and caspase-3 levels, inhibiting apoptosis.
Conclusions:
- Melatonin exerts an anti-apoptotic effect against carbon ion-induced brain cell damage.
- Melatonin's protective action is mediated by abolishing oxidative stress, increasing Nrf2 expression, and enhancing antioxidant enzyme activity.
- Melatonin effectively inhibits the mitochondrial pathway of apoptosis, offering neuroprotection.
