Toxicological assessment of the Achyrocline satureioides aqueous extract in the Caenorhabditis elegans alternative model.

Achyrocline satureioides, popularly called "marcela" in Brazil, is used in traditional medicine in South America. A. satureioides, inflorescences are used for many conditions, including to minimize the Sars-Cov-2 symptoms. Therefore, the aim of this study was to determine the toxicity profile of A. satureioides aqueous extract (ASAE), using the Caenorhabditis elegans (C. elegans) alternative model. Survival, reproduction, development, and transgenerational assays were performed. The effects of ASAE were investigated under conditions of thermal stress and presence of oxidant hydrogen peroxide (H2O2). In addition, C. elegans strains containing high antioxidant enzyme levels and elevated lineages of daf-16, skn-1 and daf-2 regulatory pathways were examined. The ASAE LC50 value was found to be 77.3 ± 4 mg/ml. The concentration of ASAE 10 mg/ml (frequently used in humans) did not exhibit a significant reduction in worm survival at either the L1 or L4 stage, after 24 or 72 hr treatment. ASAE did not markedly alter the body area. In N2 strain, ASAE (10 or 25 mg/ml) reversed the damage initiated by H2O2. In addition, ASAE protected the damage produced by H2O2 in strains containing significant levels of sod-3, gst-4 and ctl - 1,2,3, suggesting modulation in these antioxidant systems by this plant extract. ASAE exposure activated daf-16 and skn-1 stress response transcriptional pathways independently of daf-2, even under extreme stress. Data suggest that ASAE, at the concentrations tested in C. elegans, exhibits a reliable toxicity profile, which may contribute to consideration for safe use in humans.

The Aging Process Alters IL-1ß and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid.

OBJECTIVE(S): The aim of this study was to investigate exosomal markers and inflammatory cargo of extracellular vesicles (EVs) obtained from cerebrospinal fluid (CSF) and plasma in the aging process. We also studied the inflammatory cargo by quantifying IL-1ß levels. METHODS: Male Wistar rats, aged 3 and 21 months, were used (n = 12 in each group). The CSF and plasma of animals were collected, and isolation of EVs was performed using a commercial kit. Total protein concentration, acetylcholinesterase (AChE) activity, and CD63 and IL-1ß levels were evaluated. RESULTS: AChE activity in EVs increased in both samples, specifically in the circulating EVs and those in the CSF of the older group. An age-related increase was observed in CD63 levels in EVs from the CSF but a decrease was observed in plasma EVs of the older group. Student's t test showed that the young adult rats had significantly higher circulating IL-1ß levels in the EVs compared to the aged ones, without any effect on central content. CONCLUSION: Our data suggest that the normal aging process causes different changes in the profiles of central and circulating EVs. Altered IL-1ß levels in circulating EVs can be linked, at least partly, to age-related inflammatory conditions, and a disruption of the CFS exosomes in aged rats, evaluated by CD63 levels, can be related to susceptibility to neurodegenerative disorders.

Histone deacetylase activity is altered in brain areas from aged rats.

It has been described that histone acetylation levels are decreased in several cellular and in vivo neurodegeneration models as well as in normal brain aging, although the impact of the aging process on histone deacetylases (HDAC) activity yet remains poorly understood. Therefore, our aim was to evaluate the effect of the aging process on HDAC activity in hippocampi and frontal cortices from 3 and 18-months-old Wistar rats. The animals were decapitated at different times of day, in the early morning and in afternoon. HDAC activity was increased in hippocampus from the aged group. Besides, the hippocampal HDAC activity was also significantly increased in early morning. A significant interaction between age and time of the day was observed in frontal cortices, given that the HDAC activity was higher in early morning in the aged group. These data support the hypothesis that the aging-related dysfunction may be related, at least in part, to acetylation imbalance through HDAC activity in rat brain.

Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats.

The aging process is associated with cognitive impairment and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress. We determined some parameters of oxidative stress in homogenates of hippocampus, hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A significant age-dependent increase in the generation of free radicals was observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx) activity was significantly reduced in hypothalamus and hippocampus from 6-months-old rats; a decline on GPx and catalase activities in adrenal glands of 24-months-old animals was also present. Interestingly, a great decrease in total antioxidant capacity was found in all tissues tested. Reported findings support the idea that oxidative events participate on multiple neuroendocrine-metabolic impairments and suggest that the oxidative stress found in hippocampus, hypothalamus and adrenals might be associated with age-related physiological deficits.

Hippocampal antioxidant system in neonates from methylmercury-intoxicated rats.

Methylmercury (MeHg) is a well-known environmental pollutant toxic to the nervous tissue, particularly during development. We recently described transitory hippocampal changes in neonate rats prenatally exposed to MeHg. In this study, we evaluate oxidative stress in the hippocampus on the 1st and 30th postnatal days. Motor behavior (open-field, foot-fault and strength tests) of these animals also was studied after the 30th postnatal day. Female Wistar rats were injected with MeHg (5 mg/Hg/day) on the 12th, 13th and 14th gestational days. Biochemical parameters measured for oxidative stress were levels of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Total antioxidant reactivity (TAR) and protein oxidation (contents of tryptophan and tyrosine) were also recorded. Our results showed low activities of antioxidant enzymes in the MeHg group at birth. SOD activity remained reduced on the 30th postnatal day. Moreover, a decrease of TAR and protein oxidation was observed only at 30 days of age. No changes were observed in the motor behavior of these animals. Although mercury content in hippocampus is present at undetectable levels at 30 days of age, we observed more persistent changes in oxidative balance. Our data confirm that mercury induces oxidative stress in hippocampus and that this alteration, particularly SOD activity, remained altered even when mercury was no longer present.