Efeitos da associação de curcumina e piperina sobre parâmetros comportamentais e antioxidantes em um modelo da doença de Alzheimer esporádica em ratos

Abstract

Alzheimer's disease is a progressive neurodegenerative disease characterized especially by a decline in cognitive function. Considered as the biggest cause of dementia nowadays, sporadic Alzheimer's disease cover most cases and aging is the main risk factor. In this context, curcumin has aroused great interest due to its functional properties, including its antioxidant and neuroprotective action. However, curcumin's low bioavailability has encouraged the investigation of alternatives to improve its pharmacological effect. It is known that piperine promotes bioavailability increase in certain drugs when co-administered orally, including curcumin. For this reason, the aim of this study was to investigate the effects of the association of curcumin (CUR) with piperine (PIP) on behavioral parameters and antioxidants in a model of sporadic Alzheimer's disease in Wistar rats. For that, adult male Wistar rats were used, which ones were submitted to “intracerebroventricular” (ICV) administration of sterilizing solution or streptozotocin (STZ; 3 mg/kg). Afterwards, the animals received the treatment with the association of CUR/PIP (100 and 20 mg/kg, respectively) orally (VO) for 30 consecutive days. Thus, the animals were divided into four groups: 1) control group, which received sterilizing solution (ICV) and vehicle (VO); 2) CUR/PIP group, which received sterilizing solution (ICV) and association of CUR/PIP (VO); 3) STZ group, which received STZ (ICV) and vehicle (VO) and 4) STZ/CUR/PIP group, which received STZ (ICV) and CUR/PIP association (VO). After this period, the animals were submitted to different behavioral tasks to assess anxiety and cognition. Subsequently, they were euthanized in order to blood and brain collection to assess the antioxidant potential of the CUR/PIP association by measuring thiobarbituric acid reactive species (TBARS), blood glucose assessment and liver and kidney toxicity markers. The data were analyzed statistically by two-way analysis of variance (ANOVA), followed by post hoc testing when appropriate. Differences between groups were considered significant when p < 0,05. There was no statistically significant difference in motor activity, anxiety index and other parameters related with anxiety in the elevated plus- maze task. In the object recognition task, animals in the STZ group showed cognitive damage of short and long-term memories. However, animals in the STZ/CUR/PIP group showed a reversal of cognitive damage. With regard to TBARS there was no statistically significant difference between groups in the material evaluated. About the biochemical analyses, no significant differences were observed between groups for blood glucose, ALT, AST, urea and creatinine. These results indicate that the association of CUR/PIP improves cognitive damage in the used model, without influencing anxiety, locomotor parameters and also they are safe for chronic use, which may represent a strategy for its use in neurodegenerative diseases such as Alzheimer's Disease.