INTRODUCTION: Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. CONCLUSIONS: Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.
INTRODUCTION:Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epilepticpatients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epilepticpatients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epilepticpatients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epilepticwomen noticeably higher than those of epilepticmen. CONCLUSIONS: Plasma from epilepticpatients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.
Authors: Yussra Ata Yaseen Abdulqader; Hala Salah Abdel Kawy; Huda Mohammed Alkreathy; Nisreen Abdullah Rajeh Journal: Saudi Pharm J Date: 2021-04-09 Impact factor: 4.330