Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.
BackgroundThe prevalence of smokers among blood donors and the effect of smoking on the quality of donated blood have not been extensively explored. In the present study, we determined the prevalence of smoker donors in a large blood bank in Southern Brazil and evaluated the quality of packed red blood cells (RBCs) from these donors through recommended quality control tests and measurement of carboxyhemoglobin (COHb) levels. We then assessed the influence of smoking habits and abstinence before donation on these parameters.Material and methodsAn observational study was conducted to determine the prevalence of smoking donors, while a prospective cohort study compared conventional hematological and serological parameters and COHb levels at 0, 15, and 30 days after donation in RBCs donated by smokers (N = 31) and nonsmokers (N = 31) and their association with smoking habits and abstinence before donation.ResultsOf 14,428 blood donations received in 1 year, 5.9% were provided by smokers. Storage over time slightly altered some quality parameters, such as hematocrit, hemoglobin, hemolysis, and COHb levels, in RBC packs. COHb levels were higher in RBC packs from smokers (8%) than from non-smokers (2%), and increased as a function of the number of cigarettes smoked daily and time elapsed since the last cigarette smoked before donation. Lower levels were found in RBC packs from donors who smoked fewer than 20 cigarettes per day or remained abstinent for more than 12h before giving blood.ConclusionAlthough cigarette smoke had no significant effect on blood quality parameters such as hematocrit, hemoglobin, or hemolysis, it quadrupled COHb levels in packed RBCs. Abstinence from smoking for more than 12h or smoking fewer than 20 cigarettes daily helped decrease COHb levels.ImplicationsGiven the increasing prevalence of tobacco use worldwide, we suggest blood banks recommend 12h of tobacco abstinence before donation and analyze COHb levels in donated blood as an approach to reduce risk for high-risk recipients.
Major depression is more prevalent among women than men, and progesterone might be involved in the mechanisms that generate these differences. Progesterone is clinically used for women in several reproductive events, but its antidepressant effect is unclear. Animal studies showed the interference of progesterone on depressive behaviors of rodents, but they are inconclusive, and no study compared different treatment durations. This study investigated the antidepressant effect of low doses of progesterone in male and female rats under acute or chronic administration. Male and female Wistar rats in different phases of the estrous cycle were acutely administered different doses of progesterone (0.0, 0.4. 0.8 and 1.2mg/kg) and tested in the forced swimming test (FST). The lowest dose of progesterone (0.4 mg/kg) was chronically administered during two complete estrous cycles and diestrous II female and male rats were tested in the FST. Progesterone decreased depressive-like behaviors only in chronically treated diestrous II female rats and increased immobility in male rats. This low dose of progesterone did not interfere in the hormonal cycling in female rats. Results also showed that diestrous II female rats had greater immobility than male rats in the FST. The greater immobility of diestrous II female rats shows that rats in this estrous phase present more depressive-like behaviors that may be associated with their lower serum levels of progesterone. We showed that progesterone chronically administered at low doses reverses these depressive-like behaviors and has an antidepressant effect during the diestrous II phase of the estrous cycle.
Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R subunits are related to depressive-like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA(A)R α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg⁻¹) or vehicle, during two complete female estrous cycles (8-10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive-like behaviors and GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats.
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