Efeito cicatrizante do ácido alfa-lipóico em modelo animal de lesão por pressão associado às alterações comportamentais e neuroquímicas

Abstract

The development of a Pressure Injury (PI) is a very recurrent outcome in long-stay patients in hospitals or even in-home care who are bedridden. Besides raising the costs of treatment and the length of stay of the user in health services, PIs also cause suffering. This wear generated by a PI has been suggested to establish its relationship with the development of depression, a severe and disabling psychiatric disorder. In this sense, substances with antioxidant and anti-inflammatory activity are being discussed as new forms of treatment and early healing of a PI. Thus, recent studies have sought to demonstrate the healing role of alpha-lipoic acid (ALA) in skin lesions. That way, the present study aimed to investigate the wound healing effect of the topical application of ALA in an animal model of pressure injury associated with behavioral and neurochemical changes. We aimed to investigate a new therapeutic perspective for PI healing and avoid its complications. For the development of the study, we used male Swiss mice (25-30g) and separated them into the following experimental groups: control, SHAM, vehicle, ALA, and Hydrogel with Alginate. All subjects were submitted to the ischemia/reperfusion cycle (I/R) for 4 consecutive days, by placing two magnets on the skin of the dorsal region. The animals had their PI treated for 5 days topically with ALA cream or Hydrogel with Alginate and polyurethane film in the association. The control group did not have lesion induction. The vehicle group received only the ALA vehicle, and the SHAM group had the lesion-induced but received no topical treatment. The animals were submitted to the following behavioral tests: open field, splash, tail suspension, and social interaction, six hours after application of the topical treatment on days 1 and 5 of treatment. Immediately after the behavioral tests, the animals were euthanized by decapitation and their prefrontal cortex (CPF), hippocampus (HC), lesion/scar were removed, and plasma was collected for the determination of Myeloperoxidase (MPO) enzyme activity. Only the lesion/scar was used to determine the concentration of the cytokine TNF-α. The area of the lesion or scar was also removed for histopathological evaluation. Photos of the lesion were taken on days 1 and 5 of treatment. The body weight was measured at the beginning of the protocol and the end of the treatments. In the open field test, the SHAM group demonstrated a reduction in the number of crossings. while all treatments reversed this alteration. SHAM animals demonstrated an increase in immobility time in the tail suspension test. All treatments reversed this alteration. In the sucrose spray test, the SHAM group showed increased latency for grooming and decreased number and time of grooming. On the other hand, ALA cream reversed the alteration in all parameters. The other treatments only had a reversal effect on the number and time of grooming. Furthermore, SHAM animals showed a significant reduction in social interaction while all treatments reversed this modification. Furthermore, SHAM animals showed a reduction in social interaction, while all treatments managed to minimize this behavioral alteration. Concerning the behavioral assessment, the depressive-like behaviors that were mitigated due to the healing/anti-inflammatory effect of the treatments can be highlighted by: the reduction of crossings in the open field, the increase of immobility in the tail suspension; increased latency, decreased number, and time of grooming when spraying sucrose in the mice’s back, and reduced social interaction. In terms of weight variation, it was revealed that PI induction leads to a reduction in the weight of animals, on the other hand, no treatment was able to reduce. Concerning the enzymatic activity of MPO, the SHAM group showed an increase in the parameter evaluated in CPF, HC, plasma, and lesion, and the treatments reversed this effect in all tissues investigated. When assessing the TNF-α in the lesion, the SHAM group caused an increase in the concentration. All the treatments reversed this effect. About the healing effects, treatments were able to reduce the area and increase the contraction of the lesion. About the histological parameters, all treatments reduced inflammatory scores caused by PI, but only ALA was able to induce angiogenesis. Altogether, these data show that the topical treatment with ALA has a wound healing activity on PI and that this local treatment can exert an indirect antidepressant action.