Programa de Pós-Graduação em Farmacologiahttp://repositorio.ufsm.br/handle/1/23442024-03-29T06:11:40Z2024-03-29T06:11:40ZAbordagens integrativas na prevenção de recaída por morfina em ratos: organoterápico e isoterápicoFontoura, Murilo Barbozahttp://repositorio.ufsm.br/handle/1/315802024-02-27T14:15:33Z2024-01-12T00:00:00ZAbordagens integrativas na prevenção de recaída por morfina em ratos: organoterápico e isoterápico
Fontoura, Murilo Barboza
Burger, Marilise Escobar
The World Health Organization (WHO) determines drug addiction as a chronic and recurrent disease, constituting an alarming public health problem. Considering the recreational use of psychoactive drugs, such as morphine (MORPH), dependence (compulsion to use), tolerance, abstinence syndrome and relapse can be triggered after withdrawal. Reinstatement to opioid drug use is one of the main obstacles to the success of detoxification treatment, since most individuals fall back to drug use after the detoxification period. In general, the pharmacological treatments developed to date are only symptomatic, proving to be ineffective when the situation involves drug addiction. In this sense, natural therapies such as ultra-diluted medicines that aim to reestablish and integrate the organism into its homeostasis represent promising therapeutic potential in the treatment of this condition, since the dysregulation of the homeostatic balance is directly related to impulsive-compulsive, emotional, social and physical symptoms caused by the drug. This project aims to evaluate the therapeutic potential of both medicines on behavioral and molecular parameters related to MORPH reinstatement. Rats were exposed to MORPH in the conditioned place preference (CPP) paradigm to assess the drug's addictive and drug-seeking symptoms, and subsequently treated with both homeopathy medicines for 14 days. After MORPH-preference extinction, animals were challenged to MORPH reconditioning in the same CPP paradigm to evaluate MOPRH-reinstatement. Behaviors related to drug addiction, anxiety-like, memory and locomotion were assessed evaluated during drug withdrawal, followed by ex vivo assays. Our results showed MORPH-preference confirming the strong hedonic power of the drug. In the memory test and locomotor activity, no differences were observed between the groups, thus confirming the results of the CPP paradigm. Both ISO and ORG medicines prevented reinstatement-like behavior of MORPH. Molecular analysis are still being carried out. In conclusion, as far as we know, this study shows by the first time that both ultra-high dilution medicines may be an alternative which can contribute with opioid addiction reestablishing the body's physiological functions when exposed to toxic agents such as MORPH.
Universidade Federal de Santa Maria
Dissertação
2024-01-12T00:00:00ZEfeito do resveratrol per se e associado à cetamina: avaliação comportamental e de marcadores bioquímicos em camundongosJuliani, Patrícia Zorzihttp://repositorio.ufsm.br/handle/1/312192024-01-23T14:15:55Z2023-12-04T00:00:00ZEfeito do resveratrol per se e associado à cetamina: avaliação comportamental e de marcadores bioquímicos em camundongos
Juliani, Patrícia Zorzi
Fachinetto, Roselei
Schizophrenia is a serious and chronic mental illness, which affects approximately 1% of the
world's population. It is characterized by positive, negative and cognitive symptoms, which
are associated to hyperactivation of the dopaminergic mesolimbic pathway and
hypoactivation of the mesocortical pathway, respectively. The conventional treatment for
schizophrenia consists of the use of typical and atypical antipsychotics, which are not always
effective for all symptoms of the disease and around 20-30% of patients do not respond
adequately to this treatment. Then, it is important to search for new treatments and/or
therapeutic adjuvants that can be used clinically. Ketamine, a non-competitive NMDA
receptor antagonist, is used as a pharmacological agent to cause schizophrenia-like behavior
in preclinical models. Literature data demonstrate that the resveratrol (3,5,4′-trihydroxy-transstilbene), a polyphenol found in grapes and red wine, antioxidant, anti-inflammatory and
neuroprotective effects. Studies demonstrate that resveratrol modifies dopaminergic markers
in rodents increasing the availability of monoamines including dopamine. However, little is
known about its effects in experimental models of pathologies where the dopaminergic
pathways are altered, such as in schizophrenia. This study aimed to investigate if resveratrol
(at different doses) could potentiate the effects of a low dose of ketamine in schizophrenialike symptoms in mice. Male Swiss mice received a low dose of ketamine (20 mg/kg) for 14
consecutive days, and resveratrol (10, 30 or 100 mg/kg) from day 8 to day 14 of the
experimental period, both intraperitoneally. Stereotyped behavior, locomotor activity, social
interaction, special (Y-maze) and non-spatial (novel object recognition test – NORT) memory
were quantified, as well as ex vivo analysis of MAO activity, IL-6 levels and oxidative
markers (TBARS and total thiol) in brain tissues. Resveratrol (100 mg/kg) alone reduced
locomotor activity in the open field, new object exploration time in NORT and MAO-A
activity in the striatum. All of these effects were not maintained when resveratrol was
associated with ketamine. In mice treated with ketamine+resveratrol 100 mg/kg, there was a
decrease in MAO-A activity in the cortex and ketamine reduced the number of stereotyped
behavior attacks on the 8th day of the experimental period. No significant changes were found
in IL-6 levels or oxidative markers. In conclusion, resveratrol does not appear to produce
significant changes in the ketamine-induced model of schizophrenia-like symptoms in mice,
however, the effects of resveratrol per se on locomotion and NORT should be further studied.
Universidade Federal de Santa Maria
Dissertação
2023-12-04T00:00:00ZAvaliação da influência da dieta em parâmetros de estresse oxidativo, inflamação e modificações epigenéticas em pacientes com lúpus eritematoso sistêmicoSafraid, Giovana Floreshttp://repositorio.ufsm.br/handle/1/304912023-11-13T19:33:19Z2023-10-11T00:00:00ZAvaliação da influência da dieta em parâmetros de estresse oxidativo, inflamação e modificações epigenéticas em pacientes com lúpus eritematoso sistêmico
Safraid, Giovana Flores
Brucker, Natália
Exacerbated cellular activation due to autoimmunity in Systemic Lupus Erythematosus (SLE)
can generate an imbalance between antioxidants and pro-oxidants, triggering oxidative stress.
In addition to oxidative stress, chronic inflammation in SLE is a risk factor for developing
metabolic diseases. It is known that food plays an important role in modulating oxidative stress
and inflammation through the intake of nutrients that enhance or destabilize these aspects.
The study aimed to evaluate whether a diet with antioxidant and anti-inflammatory potential
can modulate oxidative stress, inflammation and epigenetic modifications in patients with SLE.
For this, a review article was first developed covering the methodologies and nutritional tools
applied to evaluate the diet profile and the influence on the progression of SLE. From the
review article, it was possible to observe that the available literature reveals a diversity in the
results investigated with heterogeneity in the methodologies and instruments for assessing
diet quality and collecting dietary data, resulting in varied conclusions about the relationship
between diet and SLE. Subsequently, a study was carried out with 40 participants, 20 patients
diagnosed with SLE and 20 control individuals. Nutritional data were collected using the food
frequency questionnaire (FFQ) and evaluated using previously validated dietary indices.
Essential and non-essential elements, biomarkers of oxidative stress and inflammation, DNA
damage, and global DNA methylation were assessed in all participants. The biomarkers of
oxidative stress, TBARS, non-protein thiols, catalase, FRAP and vitamin C did not show
significant differences between SLE patients and the control group. However, higher levels of
nitric oxide were observed in patients with SLE compared to the control group, in addition to a
positive correlation with disease activity. Patients with SLE who had more significant disease
activity had lower plasma selenium levels. An increase in the expression of β2-integrins in
neutrophils was also observed in patients with more significant renal impairment and elevated
levels of vitamin C in plasma in patients with a lower percentage of expression of ICAM-1 and
β2-integrins in neutrophils. Patients with SLE showed hypomethylation in relation to controls
and global DNA methylation negatively correlated with aspects of disease activity.
Furthermore, patients with SLE showed greater cell expression with micronuclei than controls.
Regarding food, it was observed that daily consumption of the macronutrients recommended
above may be associated with worse disease activity in patients with SLE. The dietary index
assesses the anti-inflammatory potential of the diet correlated with the lipid peroxidation
biomarker, and the dietary index assesses the antioxidant potential correlated with non-protein
thiols. Therefore, although the existing literature presents significant heterogeneity in its
conclusions, it is possible to observe that diet impacts SLE activity. Biomarkers related to
disease activity and dietary patterns that may interfere with oxidative stress were identified. A
more comprehensive evaluation of diet and SLE with a more significant number of participants
is necessary to understand biological changes better and, especially, evaluate the impact of
diet on this disease.
Universidade Federal de Santa Maria
Dissertação
2023-10-11T00:00:00ZEfeitos comportamentais e endócrinos da exposição na fase embrionária ao etonogestrel em peixe-zebraVarela, Amanda Carolina Colehttp://repositorio.ufsm.br/handle/1/304162023-10-31T18:23:41Z2023-09-18T00:00:00ZEfeitos comportamentais e endócrinos da exposição na fase embrionária ao etonogestrel em peixe-zebra
Varela, Amanda Carolina Cole
Barcellos, Leonardo Jose Gil
Improper disposal of expired drugs directly into the garbage or sewage systems
without specific treatment increases concentration of these components in wastewater.
Waste from pharmaceutical industries, used in research and treated animal waste can
contribute to this problem. Several studies have already confirmed the interference of these
compounds in embryonic growth and development, altering the behavior of exposed species
and even causing endocrine, hormonal or even genetic alterations. With use of progestins
for various purposes in human and veterinary medicine, the appearance of their residues in
natural waters has been reported. The exposure of these animals can negatively affect their
sexual development, leading to alterations such as intersex induction or changes in the
proportion of males and females. Etonogestrel (ETO) is a compound derived from 19-
nortestosteron, but it can also be found commercially in the form of a contraceptive implant.
However, few studies have evaluated its possible effects on non-target organisms in aquatic
environments, such as fish. In this study, was evaluated whether exposure to ETO in the
early stages of development causes hormonal and behavioral changes in zebrafish larvae. In
this study, embryos were exposed to 3.2 ng/L of ETO in the first five days post-fertilization.
Exposed larvae showed behavioral changes that characterize anxiety and fear-like behavior,
and also showed an increase in stress hormone levels. These results show that accidental
exposure to ETO can alter the natural behavior of fish and other non-target organisms,
leaving them susceptible to predators and other threats in the aquatic environment.
Universidade Federal de Santa Maria
Dissertação
2023-09-18T00:00:00Z