Bromocriptina na lactação atenua os efeitos deletérios do desmame precoce

Abstract

As non-pharmacological early weaning (EW) programs the offspring to obesity, liver microsteatosis and increased oxidative stress in adulthood, and the pharmacological EW, inhibiting the prolactin with a dopamine agonist (bromocriptine), also cause obesity in this study we aim to: (1) verify the redox status and hepatic function in the programming model of pharmacological EW. As bromocriptine has protective effects on glucose homeostasis in adult animals, we hypothesized that it could interfere with the programming of non-pharmacological EW and to test it we aimed: (2) to evaluate the potential interference of this drug in programming through its application in the offspring submitted to non-pharmacological EW; (3) to evaluate the long-term effects of treatment of a hyperlipidic diet. Experiment 1: lactating rats were divided into 2 groups: EW (BROMO) in which the mothers were treated i.p. with 1 mg / day of bromocriptine in the last 3 days of lactation; Control (C) whose mothers received similar treatment with vehicle solution. The offspring were evaluated at 90 and 180 days old (P90 and P180). The differences were analyzed through Student's t-test (significance P<0.05). Experiment 2: we performed a protocol where lactating rats were divided into 2 groups: non-pharmacological EW (EW) whose mothers received an adhesive bandage around the body to prevent access of pups to milk the last 3 days of lactation; Control (C) whose pups suckled freely. Thus the offspring of both groups were subdivided according to treatment: offspring that received bromocriptine (i.p. 4 mg / kg bw / day) on the last 3 days of lactation (EW/BRO and C/BRO); offspring receiving vehicle solution (EW and C). The groups were analyzed at P120. At P130 the offspring were subdivided according to the diet, constituting 8 experimental groups (C; C/BRO, EW and EW/BRO - standard chow and C-HF; C/BRO-HF, EW-HF and EW/BRO-HF - high-fat diet - 45% Kcal from lipid). The animals were followed until P200. The statistical analysis were performed by two-way ANOVA with Bonferroni post-test, one-way ANOVA with Newman-Keuls post-test and Student's t-test (between respective groups with different diets) (P<0.05). Experiment 1: we verified that the EW promoted greater visceral adiposity and dyslipidemia. At P90, BROMO offspring showed glucose intolerance, normoinsulinemia, overexpression of sirtuin-1 (SIRT-1) in the liver, increased activity of superoxide dismutase (SOD) in plasma and liver and liver glutathione peroxidase (GPx) leading to a reduced malondialdehyde (MDA) only in the liver. At P180 we observed an insulin resistance, higher GPx activity in the plasma and SOD and catalase in the liver, promoting therefore, a reduction of MDA in both tissues and preventing the onset of hepatic steatosis in the BROMO offspring, despite the decline of SIRT-1 expression. Experiment 2: The bromocriptine enhances weight loss of the pups at the end of lactation. At P120 only observed a glucose intolerance in C/BRO (remaining throughout the experiment) and adipocyte hypertrophy in the EW. Already at P200 evidenced in the EW group, greater adiposity, hyperleptinaemia, adipocyte hypertrophy, and increased hepatic triglyceride. These changes were prevented in the groups treated with bromocriptine. In contrast, the HF diet promote a greater dysfunction in the metabolism and the beneficial effects of bromocriptine were not so evident. We confirm the deleterious effects of EW and verify the therapeutic potential of bromocriptine, preventing the weight gain, adiposity and hyperleptinemia, contributing therefore, with the prevention of damage to liver tissue, when associated with an adequate dietary pattern.