Redox imbalance and inflammation: A link to depression risk in brazilian pesticide-exposed farmers.

This study aims to elucidate the mechanisms linking occupational pesticide exposure to depression among rural workers from Maravilha, Brazil. We assessed the mental health, oxidative, and inflammatory profiles of farmers exposed to pesticides (N = 28) and compared them to an urban control group without occupational exposure to pesticides (N = 25). Data on sociodemographic, occupational history, and clinical records were collected. Emotional states were evaluated using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). Biochemical, hematological, inflammatory, and redox parameters were examined in blood samples from both groups. Results showed educational disparities between groups and unveiled a concerning underutilization of personal protective equipment (PPEs) among farmers. Glyphosate was the predominant pesticide used by farmers. Farmers exhibited higher BDI scores, including more severe cases of depression. Additionally, elevated levels of creatinine, ALT, AST, and LDH were observed in farmers, suggesting potential renal and hepatic issues due to pesticide exposure. Oxidative stress markers, such as increased lipid peroxidation and superoxide dismutase (SOD) activity, along with decreased catalase (CAT) activity and ascorbic acid levels, were noted in the pesticide-exposed group compared to controls. Elevated levels of inflammatory cytokines, particularly IL-1ß, IL-6 and TNF-α, were also observed in pesticide-exposed group. Our findings suggest that inflammation, oxidative distress and lower educational levels may be associated with depression in pesticide-exposed farmers. This study highlights the impact of occupational pesticide exposure on the mental health of rural workers. The underuse of PPEs and the link between depressive symptoms, inflammation, and oxidative stress underscore the urgent need for improved safety measures in agricultural practices. Addressing these issues will contribute to a deeper understanding of the intricate relationship between environmental exposures and mental health outcomes.

Subacute exposure to Roundup® changes steroidogenesis and gene expression of the glutathione-glutaredoxin system in rat ovaries: Implications for ovarian toxicity of this glyphosate-based herbicide.

Studies have indicated that glyphosate induces endocrine disruption and may adversely affect the male reproductive system. However, evidence of its effects on ovarian function is poorly understood so far, making further studies necessary on the mechanisms of the glyphosate toxicity in the female reproductive system. The aim of this work was to evaluate the effect of a subacute exposure (28 days) to the glyphosate-based formulation Roundup® (1.05, 10.5 and 105 µg/kg b.w. of glyphosate) on steroidogenesis, oxidative stress, systems involved in cell redox control and histopathological parameters in rat ovaries. Hence we quantify plasma estradiol and progesterone by chemiluminescence; non-protein thiol levels, TBARS, superoxide dismutase and catalase activity by spectrophotometry; gene expression of steroidogenic enzymes and redox systems by real-time PCR; and ovarian follicles by optical microscopy. Our results demonstrated that oral exposure increased progesterone levels and the mRNA expression of 3ß-hydroxysteroid dehydrogenase. Histopathological analysis revealed a decrease in the number of primary follicles and an increase in the number of corpus luteum in rats exposed to Roundup®. An imbalance of the oxidative status was also evidenced by decreasing the catalase activity at all groups exposed to the herbicide. Increased lipid peroxidation and gene expression of glutarredoxin and decreased of glutathione reductase were also observed. Our results indicate that Roundup® causes endocrine disruption of hormones related to female fertility and reproduction and changes the oxidative status by altering antioxidant activity, inducing lipid peroxidation, as well as changing the gene expression of the glutathione-glutarredoxin system in rat ovaries.

Could pesticide exposure be implicated in the high incidence rates of depression, anxiety and suicide in farmers? A systematic review.

Pesticide exposure and poisoning may rise the risk of mental health problems and suicidal tendencies. To explore the potential connection between chronic occupational exposure to pesticides and depression, anxiety, and suicide-related outcomes in farmers, a systematic review was performed. Systematic review protocol is available in PROSPERO registration number CRD42022316285. A total of fifty-seven studies met inclusion criteria: twenty-nine on depression or other mental disorders, twelve on suicide (two of them on both depression and suicide), and fourteen on pesticide poisoning or self-poisoning and death. Among the fifty-seven selected studies, eighteen were conducted in Asia, seventeen in North America, fourteen in South America, seven in European Union, one in Africa, and one in Australia/Oceania. Selected studies demonstrated an increased prevalence of depressive disorders in farmworkers exposed to pesticides as well as an increased self-reported prevalence of depression in this population. Moreover, previous pesticide poisoning increased the risk estimates for depression or other mental disorders as compared with chronic pesticide exposure. Severe pesticide poisoning and multiple poisoning showed increased risks of depressive symptoms compared with milder cases. In addition, financial difficulties and poor health were positively correlated with depression. Among studies on suicide, nine of them found that suicide rates increased in areas devoted to agriculture with intensive pesticide consumption. Moreover, studies demonstrate a higher suicide risk among farmers. The present review suggests more attention to the farmer's mental health and more detailed studies on occupational exposure to the mixture of these compounds.

In vivo exposure to pyriproxyfen causes ovarian oxidative stress and inhibits follicle maturation in zebrafish.

We analyzed the effects of pyriproxyfen (PPF) on oxidative stress and ovarian morphology in zebrafish. PPF (10-9  M) exposure increased reactive oxygen species generation in ovaries, in association with a decrease in glutathione content. The activities of glutathione S-transferase, superoxide dismutase, and catalase were increased, while γ-glutamyltransferase activity was not altered by pesticide treatment. The histology of ovarian tissue showed an increase in the number of previtellogenic oocytes I, and a decrease in the rate of vitellogenic oocyte (VIT) count, suggesting inhibition of follicular maturation. An increase in the thickness of the vitelline envelope was observed in VIT, as was a tendency toward an increase in atresia in the ovary of the PPF-treated group. These findings indicate that the deleterious effect of PPF on ovarian maturation is mediated by a redox imbalance and oxidative damage. So, PPF acts as an endocrine disruptor chemical and may compromise fish reproduction by reducing female fertility.

Deregulation of purinergic ectoenzyme activity in head and neck cancer promotes immunosuppression.

BACKGROUND: Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer. METHODS AND RESULTS: We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p < 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5'-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p < 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment. CONCLUSIONS: Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.

Characterization of the chemical profile and the effects of ethanolic extracts of Maytenus ilicifolia Mart. ex Reissek on glucose metabolism in normal hyperglycemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, Celastraceae, is popularly known as "espinheira-santa" and used to treat pathologies related to the stomach. However, in popular culture, this species has also been used to treat other disorders such as diabetes, but without scientific evidence, requiring more phytochemical and pharmacological studies on the plant. AIM OF THE STUDY: This work aims to investigate the anti-hyperglycemic potential of ethanolic extracts obtained from leaves from two different accessions of Maytenus ilicifolia (MIA and MIB) in normal hyperglycemic rats. MATERIALS AND METHODS: The animals were divided into different experimental groups: normal hyperglycemic (negative control); MIA (treatment of Maytenus ilicifolia extract from access 116); MIB (treatment with Maytenus ilicifolia extract from access 122; and glipizide (positive control). At 30 min after treatment, all animals received glucose overload orally. Blood collection occurred at different periods for the assessment of blood glucose (0, 60, 90 and 210 min after treatment) and at the end of the experiment blood was collected through cardiac puncture and the liver, muscle, pancreas and intestine were dissected for further analysis. RESULTS: Chromatographic analysis identified oleic and palmitic acid as the most common constituents, and both extracts of Maytenus ilicifolia caused a reduction in blood glucose levels within 60 min after administration of glucose overload when compared to the normal hyperglycemic group. No significant changes were observed in hepatic and muscular glycogen levels, plasma insulin concentration and disaccharidases activity with none of the extracts in the model employed. However, hyperglycemic rats treated with the extracts showed a marked increase in triglyceride and HDL cholesterol levels. CONCLUSIONS: Our data suggest that Maytenus ilicifolia extracts from different locations showed differences in chemical composition which did not reflect significant differences in the results of biological tests. In addition, it was possible to conclude that the treatment with Maytenus ilicifolia had a discreet anti-hyperglycemic effect; however, it was not possible to identify the responsible mechanism, being necessary, therefore, new studies using different technologies in order to determine the possible mechanisms of action of the extract.

Pyriproxyfen induces intracellular calcium overload and alters antioxidant defenses in Danio rerio testis that may influence ongoing spermatogenesis.

We investigated the in vitro effects of pyriproxyfen on ionic balance in the testis of the zebrafish by measuring 45Ca2+ influx. In vivo pyriproxyfen treatment was carried out to study oxidative stress, and conduct morphological analysis of the testis and liver. Whole testes were incubated in vitro with/without pyriproxyfen (10-12, 10-9 or 10-6 M; 30 min) and 45Ca2+ influx determined. To study pyriproxyfen's mechanism of action, inhibitors/activators of ionic channels or pumps/exchangers, protein kinase inhibitors or a calcium chelator were added 15 min before the addition of 45Ca2+ and pyriproxyfen. We evaluated the in vivo effects of 7 day exposure to waterborne pyriproxyfen (10-9 M) on reactive oxygen species (ROS) formation, lipid peroxidation, and reduced glutathione content (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) activity. Morphological analyses of the testis and liver were carried out after in vivo exposure of D. rerio to pyriproxyfen. Pyriproxyfen increased 45Ca2+ influx by opening the voltage-dependent T-type channels (T-type VDCC), inhibiting sarco/endoplasmic reticulum 45Ca2+-ATPase (SERCA) and the NCX exchanger (forward mode) and by mobilizing calcium from stores. The involvement of potassium channels and protein kinase C (PKC) was also demonstrated in pyriproxyfen-induced intracellular calcium elevation. In vivo pyriproxyfen treatment of D. rerio increased lipid peroxidation, decreased GSH content and increased GST activity in testes, in addition to increasing the number and size of spermatogonia cysts and inducing hepatocyte basophilia and dilation of blood vessels in the liver. The toxicity of pyriproxyfen is mediated by calcium overload, increased lipid peroxidation, and a diminished antioxidant capacity in the testis, due to GSH depletion, and altered spermatogenesis. The development of high basophilia in the liver suggests that pyriproxyfen may have estrogenic activity, possibly acting as an endocrine-disruptor. These findings indicate that these alterations may contribute to pyriproxyfen toxicity and spermatogenesis disruption.

Iron and manganese present in underground water promote biochemical, genotoxic, and behavioral alterations in zebrafish (Danio rerio).

Iron (Fe) and manganese (Mn) are metals commonly found at high concentrations in underground water. These metals are essential for the good functioning of living organisms, but high concentrations lead to imbalance, potentiating the appearance of pathologies. This study aimed to evaluate the effect of exposure to naturally occurring metals in groundwater, using zebrafish (Danio rerio) as an experimental model. Thus, zebrafish were exposed to Fe (0.8 and 1.3 mg/L), Mn (0.2 and 0.4 mg/L), and groundwater collected from deep tube wells with Fe and Mn (Fe 0.8/Mn 0.2 mg/L and Fe 1.3/Mn 0.4 mg/L) for 30 days. Bioaccumulation of these metals has been demonstrated in the livers and muscles of zebrafish. Acetylcholinesterase activity changed only in zebrafish muscles in all groups. Sulfhydryl levels changed mainly in the group Mn 0.4. SOD/CAT ratio decreased in the groups Fe 0.8 and 1.3, Mn 0.4, and Fe 0.8/Mn 0.4. An increase in the frequency of micronucleus in all groups was shown as a consequence of these changes. Behavioral parameters (time and distance traveled, mean speed, turn angle, latency, and number of crossings between compartments) have also changed, mainly in the groups Fe 1.3, Mn 0.4, and Fe 1.3/Mn 0.4. Therefore, long-term exposure to Fe and Mn, even at not so high concentrations, may cause biochemical, genotoxic, and behavioral changes in zebrafish.