Avaliação do perfil antioxidante da minociclina in vitro e de seus efeitos na disbiose, nas alterações comportamentais e cardíacas causadas por dietarica em carboidratos refinados em camundongos.

Abstract

Sugar-based foods are associated with cardiac and central nervous system damage due to increased oxidative stress, altered microbiota, and increased activation of the hypothalamic-pituitary-adrenal axis. Minocycline hydrochloride is an antibiotic that has anti-inflammatory and antioxidant properties and inhibits metalloproteinases (MMPs). Therefore, we aimed to evaluate the antioxidant profile of minocycline in vitro and its effects on dysbiosis, behavioral, and cardiac changes in mice fed a diet rich in refined carbohydrates (HC). For the in vitro tests, minocycline in its raw and digested form was compared in relation to its antioxidant activity and protection against oxidation in human erythrocytes and plasma. For in vivo tests, Balb/C mice were treated with a standard diet and HC diet for 12 weeks, receiving water or minocycline (50 mg/kg) by gavage from the 10th to the 12th week. Body weight and food consumption were monitored, and at the end of the protocol, feces were collected to evaluate the microbiota and the elevated plus maze (EPM) behavioral test. After euthanasia, white adipose tissue, blood and heart were collected for the following analyses: adiposity index, biochemical analyses and evaluation of oxidative stress markers. It was observed that the digestion process increased the antioxidant activity of minocycline in in vitro chemical tests and protected erythrocytes and plasma against oxidative damage. Regarding the in vivo analyses, the animals showed increased grooming, decreased head dipping and time spent in the open arms in the EPM. Furthermore, there was a change in the microbiota with an increase in Firmicutes and a decrease in Bacteroidetes. These data indicate the development of anxietylike behavior, and minocycline partially reversed this damage. Additionally, an increase in feed consumption was observed only at the beginning of the experiment, becoming insignificant after the 4th week. Body weight was not altered; however, there was an increase in the adiposity index with changes in the lipid profile in animals fed the HC diet, accompanied by an increase in the activity of creatine kinase MB fraction, indicating damage to the myocardium. In this sense, an increase in cardiac oxidative stress caused by the diet was observed, with a decrease in glutathione, an increase in reactive oxygen species, culminating in an increase in the activity of MMPs and a consequent increase in the deposition of interstitial collagen. In addition, there was an increase in the activity of catalase and glutathione peroxidase. Minocycline showed good antioxidant activity in vitro, mainly in its digested form. Animals treated with minocycline showed improvements in their lipid profile, oxidative stress and a decrease in the percentage of collagen, suggesting that this compound can reduce the damage caused by a HC diet, acting against tissue remodeling.