Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation

Abstract

The risk of developing epilepsy is strongly linked to peripheral inflammatory disorders in humans. High-mobility group box protein 1 (HMGB1) has the most focus for being a suspect in this scenario. The current study aimed to detect the celecoxib effect, an anti-inflammatory drug, on decreasing seizure susceptibility and organ damage in lipopolysaccharides (LPS)/pilocarpine (PILO) pretreated Wistar rats. Rats were divided into 6 groups (8 each): group 1 (control), group 2 (PILO), group 3 (PILO+LPS), group 4 (PILO+LPS+(VPA) Valproic acid), group 5 (PILO+LPS+Celecoxib), and group 6 (PILO+LPS+VPA+Celecoxib). LPS was used to induce sepsis and PILO to induce seizures. Oxidative stress markers, pro-inflammatory cytokines, and HMGB1 levels in serum and brain homogenate were evaluated. Histopathological studies were conducted on the hippocampus, liver, lung, and kidney. Treatment with celecoxib either alone or in combination with VPA significantly reduced Racine score and delays latency to generalized tonic-clonic seizures onset with a significant decrease in hippocampal levels of pro-inflammatory cytokines, oxidative stress markers, and increase in reduced glutathione. In addition, celecoxib treatment either alone or in combination with VPA suppressed HMGB1translocation into peripheral circulation more than treatment with VPA alone. Furthermore, hippocampus, liver, lung, and kidney histopathological changes were improved in contrast to other epileptic groups. Celecoxib either alone or combined with VPA has antiepileptic and multiorgan protective effects on acute seizures and inflammatory models induced by PILO with LPS. It decreased histopathological findings, oxidative, and inflammatory effects induced by VPA and LPS. This might be due to its anti-oxidative, anti-inflammatory and anti-HMGB1 mediated effects.

Ursolic Acid Protects Neurons in Temporal Lobe Epilepsy and Cognitive Impairment by Repressing Inflammation and Oxidation

“…Neuronal injury is strongly associated with SE occurrence ( Alsaegh et al, 2021 ; Zhu et al, 2020 ). Therefore, we evaluated the effect of UA on hippocampal neuronal injury by Nissl staining ( Figure 4A ) and FJC staining on d 4 after SE induction ( Figures 4B–E ).…”

Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture

“…Both safinamide and celecoxib have evidence of anti-seizure activity. 46,47 SCN8A, which encodes a voltagegated sodium channel, is an established epileptic encephalopathy gene and is associated with common epilepsies for the first time here. Nav1.6 (encoded by SCN8A) is targeted by commonly used sodium channel blocking drugs that have been found to be the most efficacious ASMs for people with monogenic SCN8A-related epilepsies that are often due to channel gain-of-function.…”

Correlation Analysis of Blood Glucose Level with Inflammatory Response and Immune Indicators in Patients with Sepsis

“…CD8+ is generated during the differentiation of lymphocyte surface antigens and can identify different stages of lymphocyte development. Studies have demonstrated that CD8+ belongs to an important subgroup of T lymphocytes and exerts cell proliferation and expansion effects after differentiation to directly participate in the body's immune regulation [ 18 – 20 ]. It has been found that there is an interplay between the blood glucose level of patients with sepsis and the development of the disease.…”