Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Posttraumatic epilepsy can be modeled by intracortical iron ion injection.
• Oxidative stress, particularly hydroxyl radical (OH) generation, contributes to iron-induced seizures.
• Reactive oxygen species (ROS) play a role in neural membrane lipid peroxidation.

Purpose of the Study:

• To investigate the free radical scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on hydroxyl radicals (OH) and superoxide (O2.-).
• To evaluate the anticonvulsant properties of Ado and Cl-Ado in a rat model of FeCl3-induced epilepsy.

Main Methods:

• Electron spin resonance (ESR) spectroscopy was used to detect OH and O2.- spin adducts.
• FeCl3 was injected into the rat sensorimotor cortex to induce epileptic discharges.
• Electrocorticogram (ECoG) recordings monitored seizure activity.
• Ado and Cl-Ado were administered intraperitoneally before FeCl3 injection.

Main Results:

• Ado and Cl-Ado effectively quenched DMPO-OH spin adducts generated by the Fenton reagent.
• Neither Ado nor Cl-Ado quenched DMPO-O2.- spin adducts from the hypoxanthine-xanthine oxidase system.
• FeCl3 injection induced epileptic discharges, which were suppressed or delayed by pretreatment with Ado or Cl-Ado.

Conclusions:

• Ado and Cl-Ado exhibit scavenging activity against hydroxyl radicals (OH).
• Adenosine and 2-chloroadenosine demonstrate anticonvulsant effects in an iron-induced epilepsy model.
• These findings suggest that Ado and Cl-Ado may suppress seizures by scavenging OH radicals and exerting an anticonvulsant action.