Neuroprotective effects of chlorogenic acid against oxidative stress in rats subjected to lithium-pilocarpine-induced status epilepticus

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-09, Vol.397 (9), p.6989-6999
• Main Authors: Carreño-González, Alberth Jonnathan, Liberato, José Luiz, Celani, Marcus Vinicius Batista, Lopes, Norberto Peporine, Lopes, João Luís Callegari, Gobbo-Neto, Leonardo, Fontana, Andreia Cristina Karklin, dos Santos, Wagner Ferreira
• Format: Article
• Language: English
• Subjects: Analgesics; Animal models; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic agents; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Central nervous system; Chlorogenic acid; Chlorogenic Acid - pharmacology; Chlorogenic Acid - therapeutic use; Comorbidity; Disease Models, Animal; Drug interaction; Drug resistance; Epilepsy; Food plants; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Laboratory animals; Lithium; Lithium - pharmacology; Male; Medicinal plants; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Oxidative stress; Oxidative Stress - drug effects; Patients; Pharmacology/Toxicology; Pilocarpine; Pilocarpine - toxicity; Quality of life; R&D; Rats; Rats, Wistar; Research & development; Seizures; Side effects; Status Epilepticus - chemically induced; Status Epilepticus - drug therapy; Superoxide dismutase; Thiopental
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-024-03080-0

Epilepsy is a condition marked by sudden, self-sustained, and recurring brain events, showcasing unique electro-clinical and neuropathological phenomena that can alter the structure and functioning of the brain, resulting in diverse manifestations. Antiepileptic drugs (AEDs) can be very effective in 30% of patients in controlling seizures. Several factors contribute to this: drug resistance, individual variability, side effects, complexity of epilepsy, incomplete understanding, comorbidities, drug interactions, and no adherence to treatment. Therefore, research into new AEDs is important for several reasons such as improved efficacy, reduced side effects, expanded treatment options, treatment for drug-resistant epilepsy, improved safety profiles, targeted therapies, and innovation and progress. Animal models serve as crucial biological tools for comprehending neuronal damage and aiding in the discovery of more effective new AEDs. The utilization of antioxidant agents that act on the central nervous system may serve as a supplementary approach in the secondary prevention of epilepsy, both in laboratory animals and potentially in humans. Chlorogenic acid (CGA) is a significant compound, widely prevalent in numerous medicinal and food plants, exhibiting an extensive spectrum of biological activities such as neuroprotection, antioxidant, anti-inflammatory, and analgesic effects, among others. In this research, we assessed the neuroprotective effects of commercially available CGA in Wistar rats submitted to lithium-pilocarpine-induced status epilepticus ( SE ) model. After 72-h induction of SE, rats received thiopental and were treated for three consecutive days (1 st , 2 nd , and 3 rd doses). Next, brains were collected and studied histologically for viable cells in the hippocampus with staining for cresyl-violet ( Nissl staining ) and for degenerating cells with Fluoro-Jade C (FJC) staining. Moreover, to evaluate oxidative stress, the presence of malondialdehyde (MDA) and superoxide dismutase (SOD) was quantified. Rats administered with CGA (30 mg/kg) demonstrated a significant decrease of 59% in the number of hippocampal cell loss in the CA3, and of 48% in the hilus layers after SE. A significant reduction of 75% in the cell loss in the CA3, shown by FJC+ staining, was also observed with the administration of CGA (30 mg/kg). Furthermore, significant decreases of 49% in MDA production and 72% in the activity of SOD were seen, when compared to animals subjecte