Serum HMGB-1 and P-glycoprotein levels in epileptic patients: Associations with clinical features, seizure patterns and drug resistance

Pharmacology 2025, Belfast, İngiltere, 16 - 18 Aralık 2025, ss.108-109, (Tam Metin Bildiri)

Yayın Türü: Bildiri / Tam Metin Bildiri
Basıldığı Şehir: Belfast
Basıldığı Ülke: İngiltere
Sayfa Sayıları: ss.108-109
İstanbul Medipol Üniversitesi Adresli: Evet

Özet

Epilepsy is a serious chronic neurological disorder affecting around 70 million people worldwide, with about one third of patients showing drug resistance [1]. Therefore, elucidating the mechanisms involved in epileptogenesis and seizure generation is of great importance for the development of novel and effective treatment strategies. Clinical and experimental studies show that inflammation triggers seizures, worsens prognosis and is associated with drug resistance [2]. In addition to inflammatory mechanisms, drug efflux transporters have also been implicated in resistance. Another important protein associated with multidrug resistance, P-glycoprotein (P-gp), a member of the ABC transporter family, has been found to be overexpressed in refractory epilepsy in both clinical and in vivo studies [3]. In this context, HMGB-1 and P-gp proteins are two key biological components associated with both epileptogenesis and drug resistance mechanisms. However, to date, no studies have simultaneously evaluated the relationship between HMGB-1 and P-gp levels in patients with epilepsy. This study aims to investigate serum HMGB-1 and P-gp levels in epilepsy patients, assess their interrelationship and clinical associations and evaluate their potential as biomarkers.

Methods

The study included a total of 80 patients diagnosed with epilepsy, 40 receiving monotherapy and 40 receiving polytherapy, as well as 40 healthy volunteers. Demographic data (age and sex) for all participants, along with clinical characteristics of the epilepsy patients such as seizure frequency (presence of seizures in the last year or more than three seizures per month), seizure severity, comorbidities, drug-resistant epilepsy status and antiepileptic drugs used, were obtained from electronic medical records and medical histories. Serum samples were collected from all participants, and HMGB-1 and P-gp levels were measured using the ELISA method. Comparison of the differences between the two groups is computed using the Mann–Whitney U test. The Kruskal–Wallis H test was used for comparisons among the three groups, followed by post hoc analyses. Spearman's rank correlation was used to assess correlations between serum levels. Logistic regression and multivariate logistic regression analyses were conducted to calculate adjusted p-values. Our study was conducted in accordance with the Declaration of Helsinki and with the approval of Istanbul Medipol University Non-Interventional Clinical Research Ethics Committee, with the number E-10840098-772.02-7713. Informed consent forms were obtained from all patients and healthy volunteers included in the study.

Results

According to the multinomial logistic regression model, serum P-gp levels were significantly higher in the polytherapy group compared to the healthy control group (p = 0.021). Notably, in the polytherapy patient group, serum P-gp levels showed a positive correlation with serum HMGB-1 levels (r = 0.354*, p = 0.025) (Table 1). Also, the prevalence of drug resistance was significantly higher in the polytherapy group compared to the monotherapy group (0.125 vs. 0.875; p < 0.001). On the other hand, there was no significant difference in serum HMGB-1 levels between patient groups and controls, whereas serum P-gp levels differed significantly between groups (p < 0.001) (Table 2). Furthermore, the proportion of patients with epilepsy duration greater than 10 years was statistically higher in the polytherapy group (0.65 vs. 0.90; p = 0.007) (Table 2). Additionally, the polytherapy and monotherapy groups differed significantly in terms of seizure type (p = 0.004) (Table2). Lastly, HMGB-1 was statistically higher on monotherapy patients than polytherapy patients (OR = 5.3;p = 0.002), whereas ABCB-1 was higher on polytherapy patients (OR = 1.06;p = 0.051) (Table 3).

Conclusions

This study is the first to evaluate the relationship between serum P-gp and HMGB-1 levels in patients with epilepsy, as well as their potential as biomarkers, and a weak correlation was identified in the polytherapy group. Further studies with larger cohorts are required to confirm these associations and to elucidate their underlying mechanisms.