The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a signifi cant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These fi ndings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.

We investigated the effects of acute diazepam (DZP) administration on thiobarbituric acid-reactive substance (TBARS) levels, protein carbonyl content, and on the activities of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the brain of rats. Additionally, we investigated the antioxidant role of chronic pretreatment with simvastatin on the effects provoked by DZP. Simvastatin was administered (1 or 10 mg/kg by oral gavage) for 30 days. On the 30th day of treatment, groups were randomized and DZP was administered (0.5 or 1.0 mg/kg by intraperitoneal injection). Control groups received saline. Results showed that DZP enhanced TBARS levels and protein carbonyl content and altered enzymatic activity in the brain of rats. Simvastatin prevented most of the alterations caused by DZP on the oxidative stress parameters. Data indicate that DZP administration causes an oxidative imbalance in the brain areas studied; however, in the presence of simvastatin, some of these alterations in oxidative stress were prevented.

Introduction: Deficiency of guanidinoacetate methyltransferase, the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate (GAA) in brain and body fluids. The present study aimed to investigate the influence of GAA on the activities of antioxidant enzymes, as well as on thiobarbituric acid-reactive substances (TBARS) and butyrylcholinesterase (BuChE) activity in the blood of rats. We also evaluated the effect of trolox (6-hydr oxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), GSH (glutathione) and L-NAME (NG-nitro-L-arginine methyl ester) on the alterations elicited by GAA. Methods: The rats were randomly divided into 8 groups: (1) control; (2) GAA (10, 30, 50, 100 mM/kg); (3) trolox (1 mM/kg) + control; (4) trolox (1 mM/kg) + GAA (100 mM/kg); (5) GSH (1 mM/kg) + control; (6) GSH (1 mM/kg) + GAA (100 mM/kg); (7) L-NAME (1 mM/kg) + control; (8) L-NAME + GAA (100 mM/kg). After the addition of compounds, erythrocytes and plasma were pre-incubated at 37°C for 1h and tested immediately. Results: GAA enhanced the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in the erythrocytes and BuChE activity. In addition, GAA enhanced TBARS levels in the plasma. Trolox, GSH and L-NAME addition prevented the majority of alterations in oxidative stress parameters and the increase of BuChE activity that were caused by GAA. Data suggest that GAA alters antioxidant defenses and induces lipid peroxidation in the blood, as well altering BuChE activity. However, in the presence of trolox, GSH and L-NAME some of these alterations in oxidative stress and BuChE activity were prevented. Conclusions: Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by GAA.