Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

A doença de Parkinson (DP) é caracterizada pela degeneração progressiva dos neurônios dopaminérgicos na substância negra pars compacta. Além disso, o estresse oxidativo, presente nesta doença, causa ou contribui para o processo neurodegenerativo. Atualmente, a DP tem apenas tratamento sintomático e ainda nada pode ser feito para interromper o processo degenerativo. Este estudo teve como objetivo avaliar, comparativamente, a capacidade antioxidante do pramipexol, selegilina e amantadina em diferentes testes in vitro e oferecer possíveis explicações sobre os mecanismos moleculares antioxidantes destes fármacos. Avaliou-se a atividade antioxidante dos fármacos através da capacidade em diminuir ou sequestrar espécies reativas de oxigênio no burst respiratório, da capacidade em doar hidrogênio e estabilizar o radical livre 2,2-difenil-1-picril-hidrazil (DPPH•), de remover o radical 2,2'-azino-di-(3-etilbenzotiazolina-6-sulfônico (ABTS+) e da verificação do poder redutor/antioxidante do ferro (FRAP). Este estudo demonstrou que tanto o pramipexol como a selegilina, mas não a amantadina, possuem efeitos antioxidantes in vitro por eliminar o ânion superóxido no burst respiratório, doar elétrons no método ABTS e apresentar poder redutor sobre o ferro (FRAP). Essa capacidade antioxidante pode estar relacionada com a estrutura química desses medicamentos, sugerindo possíveis mecanismos neuroprotetores destes fármacos além de seus mecanismos de ação já conhecidos.Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Furthermore, oxidative stress plays a role in PD, causing or contributing to the neurodegenerative process. Currently PD has only symptomatic treatment and still nothing can be done to stop the degenerative process of the disease. This study aimed to comparatively evaluate the antioxidant capacity of pramipexole, selegeline and amantadine in different in vitro studies and to offer possible explanations on the molecular antioxidant mechanisms of these drugs. In vitro, the antioxidant capacity of the drugs was assessed by the ability of antiparkinsonian drugs to decrease or scavenge ROS in the neutrophil respiratory burst, ability of antiparkinsonian drugs to donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), to scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS+) and evaluation of the ferric reducing antioxidant power (FRAP). This study demonstrated that both pramipexole and selegiline, but not amantadine, have antioxidant effects in vitro by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS+ assay and presenting ferric reduction antioxidant power. This chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs beyond their already recognized mechanism of action

Effects of Inducible Nitric Oxide Synthase Inhibition on Cardiovascular Risk of Adult Endotoxemic Female Rats: Role of Estrogen

Aim: Autonomic modulation responds to ovarian hormones and estrogen increases nitric oxide bioavailability. Also, females have minor susceptibility to sepsis and a higher survival rate. However, few studies have evaluated the role of estrogen in cardiovascular, autonomic, and oxidative parameters during initial endotoxemia and under inducible nitric oxide synthase (iNOS) inhibition in female rats.Methods: Female wistar rats were subjected to ovariectomy and divided into three groups: OVX (ovariectomized), OVX+E (OVX plus daily estradiol) and SHAM (false surgery). After 8 weeks, mean arterial pressure (MAP) and heart rate (HR) were recorded in non-anesthetized catheterized rats, before and after intravenous LPS injection, preceded by S-methylisothiourea sulfate (SMT) injection, or sterile saline. Cardiovascular recordings underwent spectral analysis for evaluation of autonomic modulation. Two hours after LPS, plasma was collected to assess total radical-trapping antioxidant (TRAP), nitrite levels (NO2), lipoperoxidation (LOOH), and paraoxonase 1 (PON1) activity.Results: Two hours after LPS, females treated with SMT presented a decrease of MAP, when compared to saline-LPS groups. At this same time, all SMT+LPS groups presented an increase of sympathetic and a decrease of parasympathetic modulation of HR. Two hours after saline+LPS, OVX presented decreased total radical-trapping antioxidant (TRAP) compared to SHAM. When treated with SMT+LPS, OVX did not altered TRAP, while estradiol reduced LOOH levels.Conclusion: iNOS would be responsible for sympathetic inhibition and consumption of antioxidant reserves of females during endotoxemia, since iNOS is inhibited, treatment with estradiol could be protective in inflammatory challenges

Passiflora incarnata treatment during gestation and lactation: toxicological and antioxidant evaluation in wistar dams

Passiflora incarnata is marketed in many countries as a phytomedicine. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. In this study, a reproductive toxicity evaluation of P. incarnata was conducted in Wistar rats gavaged (30 or 300 mg/kg) during pregnancy and lactation. Moreover, considering that antioxidant properties have been attributed to flavonoids present in the genus Passiflora, it was also evaluated the antioxidant/pro-oxidant balance in the plasma of these dams and the antioxidant potential in an in vitro test. P. incarnata treatment did not influence dams´ body weight as well as reproductive (gestation length, post-implantation loss, litter size, litter weight) and hepatic (albumin, AST, ALT, GGT) parameters. The antioxidant property of P. incarnata was evidenced both in vivo (increase in the total antioxidant plasmatic potential) and in vitro (decrease in neutrophil-induced respiratory burst). The results from the present study indicate that under the experimental conditions evaluated, P. incarnata treatment during gestation and lactation presented antioxidant activity in the absence of maternal reproductive toxicity