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The present review aimed to evaluate the apoptotic effect of tributyltin (TBT) exposure on mammalian tissues and cells in vivo. A search was conducted in specialized literature databases including Embase, Medline, Pubmed, Scholar Google, and Scopus for all manuscripts using the following keywords: "tributyltin", "apoptosis", "mammals", "mammalian cells', "eukaryotic cells", 'rodents', "rats", "mice" and "in vivo" for all data published until September 2023. A total of 16 studies were included. The studies have demonstrated that TBT exposure induces apoptosis in cells from various mammalian organs or tissues in vivo. TBT is capable to increase apoptotic cells, to activate proapoptotic proteins such as calpain, caspases, bax and beclin-1 and to inhibit antiapoptotic protein bcl-2. Additionally, TBT alters the ratio of bcl-2/bax which favor apoptosis. Therefore, the activation of enzymes such as calpain induces apoptosis mediated by ERS and caspases through the intrinsic apoptosis pathway. This review has demonstrated that TBT exposure induces apoptosis in mammalian tissues and cells in vivo.

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Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science electronic databases that presented data on DNA damage caused by AAS were analyzed. A total of 15 articles were included in this study, and after thoroughly reviewing the studies, a total of 8 articles were classified as Strong, 6 were classified as Moderate, and only 1 was classified as Weak, totaling 14 studies being considered either Strong or Moderate. This classification makes it possible to consider the present findings as reliable. The meta-analysis data revealed a statistically significant difference in Wistar rat testis cells with AAS compared to control for tail length and % tail DNA (p < 0.001), so that the selected articles were considered homogeneous and the I2 of 0% indicated low heterogeneity. In summary, genotoxicity can be considered a suitable biomarker for monitoring AAS exposure as a result of DNA breakage and oxidative DNA damage.

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Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies.

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Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

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Social anxiety disorder (SAD) is a debilitating disorder, characterized by fear and anxiety in social situations. Evidence suggests that the levels of SAD are rising, in particularly after the COVID-19 pandemic. Serotonin and noradrenaline reuptake inhibitors and cognitive-behavioral therapy are effective treatments for SAD. Nevertheless, a significant number of patients do not respond well to these therapeutic options. During the last years, Cannabis and cannabinoid-containing products have been investigated for the treatment of different neuropsychiatric disorders. Nevertheless, their efficacy for the treatment of anxiety disorders is still a matter of debate. The purpose of this review was to investigate subjective, behavioral, and neurobiological effects of Cannabis and cannabinoids in social anxiety and SAD. A search in the PubMed database for articles published between the years of 2003-2023 was conducted. One hundred and seventeen (117) original studies were identified. After the exclusion criteria, eighteen (18) studies were selected. The studies investigated the effects of the cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in patients or healthy volunteers submitted to tasks that assessed social anxiety. Results showed that CBD decreases social anxiety, producing an inverted U-shaped curve, with anxiety measurements being reduced at intermediate doses administered orally (300-600 mg), but not at lower or higher doses. THC either reduces (lower doses, 6-7.5 mg) or increases (higher doses) social anxiety measurements. CBD attenuates the anxiogenic effects of THC. The effects of THC and CBD in anxiety are associated to the modulation of fronto-limbic regions. Further clinical trials, conducted with male and female patients and larger cohorts are still necessary to consolidate these results.

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The aim of this systematic review was to answer the question of whether crack cocaine can induce cellular and molecular alterations and whether such alterations are somehow related to clinical lesions in the oral mucosa. The searches were undertaken in three electronic databases and conducted based on the PRISMA 2020 statement. Eleven studies published between 1994 and 2020 were analyzed. The quality of the included studies was assessed by two independent reviewers (TGP and DAR) through a confounder's categorization methodology, in which final ratings were attributed (strong, moderate or weak) for each study. From 11 studies included, 7 evaluated the cellular/molecular impact of the addiction in a total of 492 individuals and compared to a control (non-exposure) group (n = 472). The main tests used for cellular alteration were MN and AgNORs. Cells from crack cocaine groups exhibited increased proliferation and MN counting. Only four studies evaluated the prevalence of oral lesions. All of them showed that individuals exposed to crack cocaine presented an increased number of oral lesions. Most studies showed good quality. In conclusion, our results demonstrate that crack use may induce changes at the cellular and molecular level and also exhibit an increased number of oral lesions. However, a correlation between such changes and oral mucosa lesions still needs further investigation and elucidation through other clinical studies in humans.

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PURPOSE: The aim of this study was to evaluate if the micronucleus test using oral epithelial cells is a suitable biomarker for biomonitoring children exposed to X-ray. MATERIAL AND METHODS: A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to February 2022 that examined the relationship between exposure of children to radiographic examinations and micronucleus. RESULTS: A total of 17 full-text manuscripts were screened for eligibility. Only two studies found a difference in micronucleus labeling. On the other hand, all studies showed that X-ray was able to induce cellular death in oral mucosa cells. Following the parameters of the Effective Practices in Public Health Project (EPHPP), five manuscripts reached moderate and strong scores, and four studies were categorized as weak at final rating. In the meta-analysis, statistically significant difference was detected in micronucleated cells in children before and after radiographic examinations (SMD = 0.96, 95% CI, 0.07-1.84, p = .04), with τ2=1.09; χ2=53.37, and p < .001. CONCLUSION: Radiographic examinations in children can cause genotoxic and cytotoxic damage in the oral epithelium with a large effect size.

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This work is a literature review, presenting the current state of the use of cannabinoids on neurodegenerative diseases. The emphasis is on Parkinson's (PD) and Alzheimer's (AD) diseases, the two most prevalent neurological diseases. The review goes from Cannabis sativa and its hundreds of bioactive compounds to Δ9-tetrahydrocannabinol (THC) and mainly cannabidiol (CBD) and their interactions with the endocannabinoid receptors (CB1 and CB2). CBD molecular targets were also focused on to explain its neuroprotective action mechanism on neurodegenerative diseases. Although THC is the main psychoactive component of C. sativa, and it may induce transient psychosis-like symptoms, growing evidence suggests that CBD may have protective effects against the psychotomimetic effects of THC and therapeutic properties. Furthermore, a great number of recent works on the neuroprotective and anti-inflammatory CBD effects and its molecular targets are also reviewed. We analyzed CBD actions in preclinical and in clinical trials, conducted with PD and AD patients. Although the data on preclinical assays are more convincing, the same is not true with the clinical data. Despite the consensus among researchers on the potential of CBD as a neuroprotective agent, larger and well-designed randomized clinical trials will be necessary to gather conclusive results concerning the use of CBD as a therapeutic strategy for the treatment of diseases such as PD and AD.

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This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible neurobiological mechanisms explain behavioral differences. Three different researchers conducted a search in PUBMED for all kinds of articles published between the years of 1991 to 2021 on the theme "reproductive cycle and cocaine", "estrous cycle and cocaine", "menstrual cycle and cocaine", "fluctuation of ovarian hormones and cocaine", "estrogen and cocaine" and "progesterone and cocaine". Sixty original studies were identified and subdivided into experimental rodent studies and clinical trials. Experimental studies were characterized by author/year, species/strain, sex/number, age/weight, dose/route/time of administration, hormonal assessment, or administration. Clinical trials were characterized by author/year, sex/number, age, exclusion criterion, dose/route of administration/time of cocaine, and hormonal assessment. Results gathered showed that rodent females develop increased consumption, seeking behavior, craving, relapse, locomotion, increases in stress and anxiety, among other behavioral alterations during peaks of estrogen. These observations are related to the direct effects played by ovarian hormones (in particularly estradiol), in dopamine, but also in serotonin neurons, and in brain regions such as the tegmental area, the nucleus accumbens, the hypothalamus, the amygdala and the prefrontal cortex. Increased sensitization to cocaine presented by high estradiol females was linked to the activation of a CBR1-mediated mechanism and GABA-A-dependent suppression of inhibitory synaptic activity of the prelimbic prefrontal cortex. Estradiol facilitation of cocaine-increased locomotion and self-administration was shown to require the release of glutamate and the activation of metabotropic glutamate receptors subtype 5. Clinical studies also tend to point to a stimulatory effect of estradiol on cocaine sensitization and a neuroprotective effect of progesterone. In conclusion, the results of the present review indicate a need for further preclinical and clinical trials and neurobiological studies to better understand the relationship between sex and ovarian hormones on cocaine sensitization.

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Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.

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The systematic review (SR) with meta-analysis aimed to infer if micronucleus assay using oral mucosal cells a useful biomarker for biomonitoring populations continuously exposed to pesticides (EP). The SR has been made in accordance with the PRISMA-P guidelines. The PICOS strategy has focused to answer the following question: "Does exposure to pesticides cause genetic damage in oral cells?" The literature search was made in the following scientific databases: Web of Science, PubMed/Medline, and Scopus. The approach was defined as follows: standardized mean difference (SMD) and 95% confidence intervals (CI). The quality assessment of manuscripts was obtained by the EPHPP (Effective Public Health Practice Project). The GRADE tool was chosen for assessing the quality of evidence. A total of 108 articles were selected in this setting. After screening abstracts and titles, 23 manuscripts were evaluated for eligibility. After reviewing the studies, two were considered weak and 22 were classified as moderate or strong. The meta-analysis data pointed out statistically significant differences in volunteers exposed to EP (SMD = 1.23, 95% CI, 0.69 to 1.77, p < 0.001), with a Tau2 = 1.44; Chi2 = 566.38, and p < 0.001, so that the selected manuscripts were considered heterogeneous and the I2 of 97% indicated high heterogeneity. Taken together, this review was able to validate the micronucleus assay in oral exfoliated cells as a useful biomarker in individuals continuously exposed to EP because the studies categorized as moderate and strong have demonstrated positive response related to mutagenesis.

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In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.

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This systematic review (SR) with meta-analysis aimed to evaluate the scientific data related to cytogenetic damage in oral exfoliated cells of patients diagnosed with oral potentially malignant disorders (OPMDs). The SR was conducted according to the PRISMA-P guidelines. The PICOS (Participants, Intervention, Comparison, Outcome, and Study Design) strategy was used to answer the question: "Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with OPMDs?" The search strategy was performed in the following electronic databases: PubMed, Medline, Scopus and Web of Science. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CI). The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). The GRADE tool was also utilized to assess the quality of evidence of the SR. A total of 110 potentially relevant studies were selected through the search strategy. After screening titles and abstracts, 20 full-text manuscripts were assessed for eligibility and three observational studies were included in the meta-analysis. After reviewing the 20 studies, 13 were considered weak. The meta-analysis data revealed a statistically significant difference in oral micronucleated cells by patients with OPMDs when compared to control (SMD=1.77, 95% CI, 0.36-3.18, p = 0.01), with a Tau2 = 1.97; Chi2 = 66.64, and p < 0.001. Patients with OPMDs had a positive response related to mutagenicity in oral cells compared to control patients. However, SR was not able to validate the micronucleus assay as a putative biomarker in individuals with oral potentially malignant disorders since the majority of studies were considered weak based on high risk of bias.

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Elevated levels of endogenous ovarian hormones are conditions commonly experienced by women undergoing assisted reproductive technologies (ART). Additionally, infertility-associated stress and treatment routines are factors that together may have a highly negative impact on female emotionality, which can be aggravated when several cycles of ART are needed to attempt pregnancy. This study aimed to investigate the effect of high and fluctuating levels of gonadal hormones induced by repeated ovarian stimulation on the stress response in rodents. To mimic the context of ART, female rats were exposed to an unpredictable chronic mild stress (UCMS) paradigm for four weeks. During this time, three cycles of ovarian stimulation (superovulation) (150 IU/Kg of PMSG and 75 IU/Kg of hCG) were applied, with intervals of two estrous cycles between them. The rats were distributed into four groups: Repeated Superovulation/UCMS; Repeated Superovulation/No Stress; Saline/UCMS; and Saline/No Stress. Anxiety-like and depressive-like behaviors were evaluated in a light-dark transition box and by splash test, respectively. Corticosterone, estradiol, progesterone, and biometric parameters were assessed. Data were analyzed using a two-way Generalized Linear Model (GzLM). Our results showed that repeated ovarian stimulation exerts by itself an expressive anxiogenic effect. Surprisingly, when high and fluctuating levels of ovarian hormones were combined with chronic stress, anxiety-like behavior was no longer observed, and a depressive-like state was not detected. Our findings suggest that females subjected to emotional overload induced by repeated ovarian stimulation and chronic stress seem to trigger the elaboration of adaptive coping strategies.

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The aim of this study was to investigate histopathological and inflammatory response in liver and kidney of rats after crack exposure. For this purpose, a total of 32 male Wistar rats were distributed into four groups: (G1) and (G2): received 18 mg/kg of body weight (b.w) of crack cocaine, but Group G2 remained 72 h without exposure after the experimental period (5 days). Experimental group 3 (G3): received 36 mg/kg of body weight (b.w) of crack cocaine. Control Group (CTRL): received only the vehicle (DMSO) administered by intraperitoneal (i.p) route for 5 days. The results showed that crack cocaine induced histopathological changes in liver and kidney. Immunohistochemistry data revealed that G2 group showed a higher immunoexpression of Ki-67 in hepatic and renal tissues. Regarding inflammation, the results showed that all groups exposed to crack cocaine decreased the expression of TNF-α, IL-6, and IL-10 in liver and kidney. In summary, our results showed that the subacute doses of crack cocaine used in this study had cytotoxic, and immunosuppressive effects in liver and kidney of rats, especially at 36 mg/kg dose. Since cellular death and inflammation participates in the multi-step process of chemical carcinogenesis, these data offer new insights into potential ways to understand the pathobiological mechanisms induced by crack cocaine in several tissues and organs.

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AIM: The aim of this review was to evaluate the scientific literature regarding the cytogenetic damage in oral exfoliated cells of adult patients submitted to panoramic X-ray. MATERIALS AND METHODS: An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all studies published until April 2021 using combinations of the following keywords: "panoramic X-ray," "DNA damage," "genetic damage", "genotoxicity", "mutagenicity", cytotoxicity", "buccal cells", "oral mucosa", "tongue", "gingiva", "micronucleus assay", according to the PRISMA guidelines. All clinical studies in English language were included in the study. A total of 10 studies were identified. RESULTS: As expected, the results regarding the cytogenetic damage induced by panoramic X-ray are conflicting. Some authors have demonstrated that panoramic X-ray induces mutagenesis in oral cells, whereas others did not. After reviewing the 10 studies, two were classified as strong, four were considered moderate, and four were considered weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed a negative response related to mutagenicity in oral cells by panoramic X-ray. CONCLUSION: Taken together, this review failed to demonstrate the association between micronucleus frequency and panoramic X-ray.

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BACKGROUND/AIM: The aim of the present study was to investigate the biological effects of subacute crack cocaine exposure in rat liver. MATERIAL AND METHODS: A total of 32 rats were distributed into four groups (n=8): Experimental group 1 (G1) and Experimental group 2 (G2): rats received 18 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day, group G2 remained 72 h without exposure after the experimental period (5 days)(abstinence); Experimental group 3 (G3): rats received 36 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day; Control Group (CTRL): rats received only the vehicle (DMSO) administered by the intraperitoneal (i.p) route for 5 days, once a day. RESULTS: All groups exposed to crack cocaine had an increase in the number of micronucleated hepatocytes and binucleated cells only in the highest tested dose (36 mg/kg). Karyolysis had an increase in the 18 mg/kg dose, in the abstinence group (G2), and 36 mg/kg group (G3); whereas pyknotic nuclei had an increase in the G2 group. The group exposed to 18 mg/kg of crack cocaine also showed high 8 OHdG expression. The p-NF-κB p65 protein decreased in the groups exposed to crack cocaine at doses of 18 and 36 mg/kg, as well as in the abstinence group. MyD88 was also found decreased in the group exposed to crack cocaine at 18 mg/kg. CONCLUSION: Crack cocaine inhibited toll like signaling pathway whilst being associated with genomic instability in rat liver cells.

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