Marcadores de estresse oxidativo em pacientes com epilepsia do lobo temporal mesial

Abstract

Epilepsy, a chronic neurological condition of heterogeneous etiology, affects around 50 million people worldwide. Temporal lobe epilepsy (TLE), with an estimated prevalence of 20-25%, induces complex biochemical, physiological, molecular and structural changes in the brain. Temporal mesial sclerosis (TMS) is one of the lesions most frequently associated with TLE. There is a high prevalence of psychiatric disorders (PD) in patients with TLE-TMS, whose pathophysiological mechanisms may be correlated. The study of oxidative stress, due to the imbalance between the production of oxidant compounds and the activity of the antioxidant defense system, may contribute to the understanding of the biological basis of TLE-TMS. Objectives - To evaluate the association of oxidative stress markers with TLE-TMS in patients resistant to drug treatment, with and without PD. Patients and Methods - We studied 98 individuals, distributed in three groups: G1 -25 patients diagnosed with TLE-TMS refractory without PD; G2 - 21 patients with refractory TLE-TMS and PD; G3 - 52 individuals without diagnosis of epilepsy (Control Group). Oxidative stress markers, including catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione plus oxidized glutathione (GSH-t), glucose-6-phosphate dehydrogenase (G6PD), trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid reactive substances (TBARS) by spectrophotometry. Clinical / demographic / social profile and life habits were obtained by means of a questionnaire and medical records. A 5% alpha error was allowed. Results – The groups showed similarity for sex, smoking, alcoholism and comorbidities (P> 0.05). Familial history of epilepsy prevailed in patients compared to controls (G1=60%; G2=57.1%; G3=15.4%; P=0.0002 and P=0.0009, respectively). For the social profile, lower financial income was observed in patients (G1=48%; G2=42.9%), compared to controls (G3=90.4%; P=0.0003 and P<0.0001; respectively); the same occurred for higher level education (G1=4%; G2=4.8%; G3=63.5%; P<0.0001 and P<0.0001; respectively). In relation to the markers of oxidative stress, CAT levels were increased in patients (G1=15,901±5,395.5U/mL; G2=16,334±5,815.8U/mL), compared to controls (G3=10,155±4,286.2U/mL; P<0.0001), as well as TBARS (G1=569.73±694.35ng/mL, G2=506.13±598.08ng/mL; G3=180.23±47.09ng/mL; P=0.0013). On the other hand, patients presented a reduction in GPx levels (G1=4.81±1.54U/mL; G2=4.81±1.40U/mL), G6PD (G1=0.91±0.32U/mL; G2=0.85±0.24U/mL) and GSH-t (G1=0.53±0.15mM; G2=0.55±0.15mM), compared to controls (G3=7.06±1.81U/mL; 1.10±0.32U/mL; 0.66±0.27mM; P<0.0001; P=0.0057; P=0.0454). There was a negative correlation between TBARS and GPx in G2 (R=-0.5151; P=0.0240); however, there was a positive correlation in the control group between GR and G6PD (R=0.2854; P=0.0403), GPx and G6PD (R=0.3362; P=0.0148); GSH-t and G6PD (R=0.2950; P=0.0338) and GPx and GSH-t (R=0.5977; P<0.0001). Conclusion - Reduced values of GPx, G6PD and GSH-t and increased CAT in patients with or without PD indicate a demand for antioxidants on the combat against oxidative stress in TLE-MTS, but not always effective as shown by the increase in TBARS, a marker of lipid peroxidation. The correlation between oxidative stress markers reflects the integration of antioxidant systems and lipid peroxidation. It is also worth to point out the persistence of pre-established social stigmas in patients with TLE-MTS, related to socioeconomic-educational profile, as well as genetic character associated with the disease.