ABSTRACT
PURPOSE/BACKGROUND: Accumulating evidence suggests an involvement of oxidative stress in the pathophysiology of schizophrenia. This offers a hypothesis-derived therapeutic approach to hinder oxidative damage and its clinical sequelae. α-Lipoic acid (ALA) is a powerful natural antioxidant indicated to treat diabetic neuropathy. METHODS/PROCEDURES: In this pilot investigation, we administered ALA (100 mg/d) for 4 months, as an adjunct to antipsychotic medication, to 10 patients with schizophrenia. FINDINGS/RESULTS: We found robust improvement in measures of psychopathology (63.9% reduction in Brief Psychiatric Rating Scale scores), neurocognitive parameters, extrapyramidal symptoms, and decreased lipid peroxidation. IMPLICATIONS/CONCLUSIONS: If larger, double-blind, placebo-controlled studies confirm these preliminary findings, ALA could prove useful as adjunctive therapy for schizophrenia.
Subject(s)
Antioxidants/pharmacology , Antipsychotic Agents/pharmacology , Outcome Assessment, Health Care , Schizophrenia/drug therapy , Thioctic Acid/pharmacology , Adult , Antioxidants/administration & dosage , Antipsychotic Agents/administration & dosage , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Pilot Projects , Thioctic Acid/administration & dosageABSTRACT
Some proteins present in snake venom possess enzymatic activities, such as phospholipase A(2) and l-amino acid oxidase. In this study, we verify the action of the Bothrops marajoensis venom (BmarTV), PLA(2) (BmarPLA(2)) and LAAO (BmarLAAO) on strains of bacteria, yeast, and Leishmania sp. The BmarTV was isolated by Protein Pack 5PW, and several fractions were obtained. Reverse phase HPLC showed that BmarPLA(2) was isolated from the venom, and N-terminal amino acid sequencing of sPLA(2) showed high amino acid identity with other lysine K49 sPLA(2)s isolated from Bothrops snakes. The BmarLAAO was purified to high molecular homogeneity and its N-terminal amino acid sequence demonstrated a high degree of amino acid conservation with others LAAOs. BmarLAAO was able to inhibit the growth of P. aeruginosa, C. albicans and S. aureus in a dose-dependent manner. The inhibitory effect was more significant on S. aureus, with a MIC=50 microg/mL and MLC=200 microg/mL. However, the BmarTV and BmarPLA(2) did not demonstrate inhibitory capacity. BmarLAAO was able to inhibit the growth of promastigote forms of L. chagasi and L. amazonensis, with an IC(50)=2.55 microg/mL and 2.86 microg/mL for L. amazonensis and L. chagasi, respectively. BmarTV also provided significant inhibition of parasitic growth, with an IC(50) of 86.56 microg/mL for L. amazonensis and 79.02 microg/mL for L. chagasi. BmarPLA(2) did not promote any inhibition of the growth of these parasites. The BmarLAAO and BmarTV presented low toxicity at the concentrations studied. In conclusion, whole venom as well as the l-amino acid oxidase from Bothrops marajoensis was able to inhibit the growth of several microorganisms, including S. aureus, Candida albicans, Pseudomonas aeruginosa, and Leishmania sp.