Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition.

The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Prednisona e meloxicam no tratamento de ratos submetidos ao trauma agudo da medula espinhal / Prednisone and meloxicam in the treatment of rats underwent to acute spinal cord injury

O objetivo deste estudo foi investigar o efeito da prednisona e do meloxicam na terapia de ratos submetidos ao modelo experimental de trauma agudo da medula espinhal, induzida pelo cateter de Fogarty 2Fr, mediante a avaliação dos parâmetros de estresse oxidativo, dos testes neurológicos e do exame histopatológico da medula espinhal. Foram utilizados 90 ratos Wistar, distribuídos em seis grupos, denominados controle salina ou GCS (n=15), controle prednisona ou GCP (n=15), controle meloxicam ou GCM (n=15), trauma mais salina ou GTS (n=15), trauma mais prednisona ou GTP (n=15) e trauma mais meloxicam GTM (n=15). Cada grupo foi redistribuído em três subgrupos de igual número, de acordo com o tempo de tratamento no pós-operatório de 24h, 72h e sete dias. Todos os grupos foram submetidos à laminectomia e, nos grupos GTS, GTM e GTP, após a exposição da medula espinhal, foi realizado o trauma medular compressivo, utilizando o cateter de Fogarty 2Fr. Os grupos GCS e GTS foram tratados com solução salina, os GSM e GTM receberam meloxicam e os GSP e GTP prednisona, sendo administrados pela via intraperitoneal. Em todos os ratos, foram avaliados os parâmetros de estresse oxidativo, testes neurológicos e exame histopatológico da medula espinhal. Os animais dos grupos GTS, GTM e GTP, nos diferentes tempos (24h, 72h e sete dias), tiveram pontuação zero na escala de Basso, Beattie e Bresnahan (BBB); no plano inclinado, permaneceram com pontuação três e perderam a percepção da dor profunda. Os grupos GTM e GTP apresentaram menor atividade da catalase e de níveis de TBARS, quando comparado ao grupo GTS. Foi constatada degeneração Walleriana e necrose da substância cinzenta de intensidades variáveis, não apresentando diferença entre os grupos submetidos ao trauma. O meloxicam e a prednisona apresentam possível efeito antioxidante, mas não impedem a necrose e a degeneração Walleriana da medula espinhal de ratos.

The aim of the study was investigate the use of the prednisone and meloxicam in treatment of rats underwent to the experimental model of acute spinal cord injury with 2Fr Fogarty catheter, with evaluation of the oxidative stress, neurological test and histopathological analysis of the spinal cord. Ninety rats were separated into six equal groups denominated saline control or SCG, prednisone control or PCG, meloxicam control or MCG, saline and injury or STG, prednisone and injury PTG and meloxicam and injury MTG. Each group was divide into three subgroups according to treatment time in the postoperative period of 24h, 72h and seven days. All the rats underwent laminectomy and in the groups STG, MTG and PTG, after exposure of the spinal cord it was performed a compressive spinal cord injury with a 2Fr Fogarty catheter. The SCG and STG were treated with saline, MSG and MTG, with meloxicam and PSG and PTG with prednisone. All rats were evaluated for oxidative stress, neurological tests and histopathology of the spinal cord. Neurological tests were performed with Basso, Beattie e Bresnahan score (BBB), inclined plane and deep pain 24 hours before and after surgery and repeated every 48 hours until the day of euthanasia. The groups STG, MTG and PTG in the different times were zero point in the BBB scale and three points in the inclined plane and absence of deep pain. MTG and PTG had lower catalase activity and TBARS levels when compared to the STG. In the histopathological analysis it was found Wallerian degeneration and necrosis of gray matter of intensity variation. Meloxicam and prednisone can exhibit antioxidant effect, but the necrosis and Wallerian degeneration were not stop in rats underwent to acute spinal cord injury.