Does valproate therapy in epileptic patients contribute to changing atherosclerosis risk factors? The role of lipids and free fatty acids.

BACKGROUND: We aimed to demonstrate the relationship between the valproate (VPA) treatment versus lipid and serum free fatty acids (FFAs) profiles to be the potential atherosclerosis risk factor in epileptic patients. METHODS: Fasting blood samples were taken from 21 adult VPA-treated patients and 21 controls. The profiles of lipids, FFAs, clinical parameters and body mass index (BMI) were evaluated. RESULTS: No significant differences between the study group and controls were found for any of the studied parameters. However, significant differences in the total cholesterol (CHOL), low-density-lipoprotein cholesterol (LDL), triglycerides, the CHOL/HDL (high-density-lipoprotein cholesterol) ratio, and Atherogenic Index of Plasma were observed for overweight patients when compared to those of normal weight. Patients with uncontrolled epilepsy tended to have significantly lower palmitic acid level than seizure-free patients. Oleic acid was found to be positively correlated with VPA concentration for patients with uncontrolled epilepsy, and with the dose corrected VPA concentration for all the patients. The acid was however negatively correlated with stearic acid for both the controls and the patients with uncontrolled epilepsy. PLS method revealed CHOL, LDL, triglycerides and myristic acid to be positively interrelated for the whole group under the study, whereas these parameters were found to be negatively correlated with VPA concentration, and positively with BMI. Furthermore, high sensitivity C-reactive protein was found to be negatively correlated with palmitic acid levels. CONCLUSION: Overweight VPA-treated patients are exposed to higher risk of atherosclerosis. Alterations in FFAs are likely to depend on seizures control, and on VPA levels.

Antioxidant agents and physiological responses in adult epileptic patients treated with lamotrigine.

BACKGROUND: The aim of our research was to evaluate some biochemical changes in blood during lamotrigine (LTG) monotherapy of adult patients with epilepsy, and to check possible associations between typical selenium status parameters and the frequency of seizures. METHODS: The study was performed by examining aspartate aminotransferase (AspAT), alanine aminotransferase (AlaAT), creatinine, ferric reducing ability of plasma (FRAP), serum uric acid (UA), uric-acid-independent FRAP (UAiFRAP), plasma glutathione peroxidase (GPX3), selenoprotein P (SelP), plasma superoxide dismutase (pSOD), 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum and urine, serum selenium (sSe) and zinc (sZn), in 22 adult patients with epilepsy and 22 healthy controls. Additionally, the levels of LTG were determined in patients. RESULTS: pSOD activity was higher in the study group (5.32±1.24 U/ml) compared with the controls (4.05±0.92 U/ml, p=0.008). No other statistical difference between patients and controls was found. CONCLUSION: Lack of difference in parameters other than SOD, particularly no difference in 8-OHdG concentrations between the patients treated with LTG compared to the control subjects suggests that these patients are at no particular risk of oxidative DNA damage. In patients who are well or moderately well clinically controlled, selenium status parameters (sSe, GPX3, SelP) are not directly connected with the frequency of seizures.

Valproic acid modulates superoxide dismutase, uric acid-independent FRAP and zinc in blood of adult epileptic patients.

We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7-14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.

Antioxidant nutrients and mycotoxins.

Mycotoxins are fungal secondary metabolites that are toxic to vertebrates produced by organisms that occur as plant pathogens, soilborne fungi, airborne fungi and aeroallergens. They are distributed worldwide and may be recovered from a wide range of substrates. Their presence in food and feeds, as the result of fungal diseases in crops, can present a danger to animal and human health. Many mycotoxins have also been shown to be phytotoxic and in some cases, such as with trichothecenes produced by the wheat head blight fungus Fusarium graminearum, mycotoxins may act as virulence factors. Several natural (vitamin, provitamins, carotenoids, chlorophyll and its derivatives, phenolics, and selenium) and synthetic (butylated hydroxyanisole and butylated hydroxytoluene) compounds with antioxidant properties seem to be potentially very efficacious in protecting against the toxic effects of mycotoxins. The protective properties of antioxidants are probably due to their ability to act as superoxide anion scavengers, thereby protecting cell membranes from mycotoxin-induced damage and in some cases, antioxidant vitamins may play a role in preventing mycotoxicosis. However, much less information is available from studies carried out on antioxidants and mycotoxins, such as OTA, FB(1), T-2 toxin, ZEN, and citrinin. No such studies have been performed on recently discovered toxins such as beauvericin, fusaproliferin, moniliformin, and fusaric acid. However, supplementation with antioxidant nutrients to prevent mycotoxicosis has been controversial. The case for the use of supplemental antioxidant vitamins at the present time needs further research.