Rosmarinic acid improves oxidative stress parameters and mitochondrial respiratory chain activity following 4-aminopyridine and picrotoxin-induced seizure in mice
Studies have indicated that epilepsy, an important neurological disease, can generate oxidative stress and mitochondrial dysfunction, among other damages to the brain. In this context, the use of antioxidant compounds could provide neuroprotection and help to reduce the damage caused by epileptic seizures and thereby the use of anticonvulsant drugs. Rosmarinic acid (RA) is an ester of caffeic acid and 3,4-dihydroxyphenylactic acid that prevents cell damage caused by free radicals, acting as an antioxidant. It also presents anti-inflammatory, antimutagenic, and antiapoptotic properties. In this work, we used two models of acute seizure, 4-aminopyridine (4-AP) and picrotoxin (PTX)-induced seizures in mice, to investigate the anticonvulsant, antioxidant, and neuroprotective profile of RA. Diazepam and valproic acid, antiepileptic drugs already used in the treatment of epilepsy, were used as positive controls. Although RA could not prevent seizures in the models used in this study, neither enhance the latency time to first seizure at the tested doses, it exhibited an antioxidant and neuroprotective effect. RA (8 and 16 mg/kg) decreased reactive oxygen species production, superoxide dismutase activity, and DNA damage, measured in hippocampus, after seizures induced by PTX and 4-AP. Catalase activity was decreased by RA only after seizures induced by 4-AP. The activity of the mitochondrial complex II was increased by RA in hippocampus samples after both seizure models. The results obtained in this study suggest that RA is able to reduce cell damage generated by the 4-AP and PTX seizures and therefore could represent a potential candidate in reducing pathophysiological processes involved in epilepsy.
Keywords4-aminopyridine Mitochondrial respiratory chain Oxidative stress Picrotoxin Rosmarinic acid Seizure
The authors were supported by the Brazilian’s agencies: National Council for Scientific and Technological Development (CNPq) (Dr. Guilhian Leipnitz and Dr. P Pereira), and Federal University of Rio Grande do Sul (UFRGS).
JGL, LS, AMM, MSR, and DG conducted the behavioral and biochemical experiments. GRG and PFP analyzed data. GL, DJM, JGL, and PP developed the experimental design, analyzed the data, and wrote the paper. All authors read and approved the manuscript.
Compliance with ethical standards
Experimental protocol adhered to the Guidelines of Brazilian Council of Animal Experimentation—CONCEA—and EU Directive 2010/63/EU for animal experiments.
Conflict of interest
The authors declare that they have no conflict of interest.
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