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Does trimetazidine exert cytoprotective activity on astrocytes subjected to hypoxia in vitro?
B Gabryel1, M Adamek, H I Trzeciak
1Department of Pharmacology, Silesian Medical University, Katowice, Poland. phacom@promarcos.com.pl
Abstract:
The aim of the present study was to establish whether trimetazidine (TMZ) is capable of protecting astrocytes against hypoxic injury. Using the model of astrocyte cell culture we tried to observe the cells treated with TMZ before, during and after hypoxia simulated in vitro. Cell viability was determined by Live/Dead (viability/cytotoxicity) Assay Kit and MTT conversion test. Apoptotic cell death was distinguished by a method using fluorescence microscopy with Hoechst 33342. The effect of the drug on the DNA synthesis was evaluated by measuring the incorporation of [3H]thymidine into DNA of astrocytes. TMZ stimulates the proliferation of astrocytes most significant one when the astrocytes are exposed to the drug in normoxia, hypoxia and/or re-oxygenation. Adding TMZ into cultures during re-oxygenation and hypoxial re-oxygenation significantly decreases the number of dead and apoptotic cells. Our experiment has proved that TMZ exerts the most significantly cytoprotective effect on astrocytes in vitro when added during hypoxia and/or re-oxygenation. We may conclude that the protective effect of TMZ depends on the sequence of drug adding and hypoxia/ re-oxygenation onset.
Insights
Trimetazidine (TMZ) protects astrocytes from hypoxic injury. Adding TMZ during hypoxia or re-oxygenation significantly reduces cell death and apoptosis, highlighting its cytoprotective role.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Astrocytes play crucial roles in central nervous system function.
- Hypoxic injury can lead to astrocyte dysfunction and death.
- Trimetazidine (TMZ) is a drug with potential cytoprotective properties.
Purpose of the Study:
- To investigate the protective effects of trimetazidine (TMZ) against hypoxia-induced injury in astrocytes.
- To determine the optimal timing for TMZ administration to maximize its cytoprotective effects.
Main Methods:
- Primary astrocyte cell cultures were subjected to simulated in vitro hypoxia.
- Cells were treated with TMZ before, during, or after hypoxic exposure.
- Cell viability was assessed using Live/Dead assay and MTT test.
- Apoptotic cell death was quantified via Hoechst 33342 staining and fluorescence microscopy.
- DNA synthesis was measured by [3H]thymidine incorporation.
Main Results:
- TMZ stimulated astrocyte proliferation, particularly when added during normoxia, hypoxia, and/or re-oxygenation.
- Administration of TMZ during re-oxygenation and hypoxic re-oxygenation significantly reduced the number of dead and apoptotic cells.
- The most significant cytoprotective effect of TMZ on astrocytes in vitro was observed when added during hypoxia and/or re-oxygenation.
Conclusions:
- The cytoprotective effect of TMZ against hypoxic injury in astrocytes is sequence-dependent.
- TMZ demonstrates significant efficacy in protecting astrocytes when administered during critical phases of hypoxia and re-oxygenation.
