Artigos - Princípios Ativos Naturais e Toxicologia - FCFAR

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Anterior cingulate cortex, but not amygdala, modulates the anxiogenesis induced by living with conspecifics subjected to chronic restraint stress in male mice
(2023-01-06) Silveira, Lara Maria; Tavares, Ligia Renata Rodrigues [UNESP]; Baptista-de-Souza, Daniela [UNESP]; Carmona, Isabela Miranda [UNESP]; Carneiro de Oliveira, Paulo Eduardo; Nunes-de-Souza, Ricardo Luiz [UNESP]; Canto-de-Souza, Azair [UNESP]; Universidade Federal de São Carlos (UFSCar); Universidade Estadual Paulista (UNESP); Institute of Neuroscience and Behaviour
Cohabitation with a partner undergoing chronic restraint stress (CRE) induces anxiogenic-like behaviors through emotional contagion. We hypothesized that the anterior cingulate cortex (ACC) and the amygdala would be involved in the modulation of this emotional process. This study investigated the role of the ACC and amygdala in empathy-like behavior (e.g., anxiety-like responses) induced by living with a mouse subjected to CRE. Male Swiss mice were housed in pairs for 14 days and then allocated into two groups: cagemate stress (one animal of the pair was subjected to 14 days of restraint stress) and cagemate control (no animal experienced stress). Twenty-four hours after the last stress session, cagemates had their brains removed for recording FosB labeling in the ACC and amygdala (Exp.1). In experiments 2 and 3, 24 h after the last stress session, the cagemates received 0.1 μL of saline or cobalt chloride (CoCl2 1 mM) into the ACC or amygdala, and then exposed to the elevated plus-maze (EPM) for recording anxiety. Results showed a decrease of FosB labeling in the ACC without changing immunofluorescence in the amygdala of stress cagemate mice. Cohabitation with mice subjected to CRE provoked anxiogenic-like behaviors. Local inactivation of ACC (but not the amygdala) reversed the anxiogenic-like effects induced by cohabitation with a partner undergoing CRE. These results suggest the involvement of ACC, but not the amygdala, in anxiety induced by emotional contagion.
The Reversal of Empathy-Induced Hypernociception in Male Mice by Intra-Amygdala Administration of Midazolam and Cannabidiol Depends on 5-HT3Receptors
(2023-04-01) Rodrigues Tavares, Ligia Renata [UNESP]; Baptista-De-Souza, Daniela [UNESP]; Canto-De-Souza, Lucas [UNESP]; Planeta, Cleopatra Da Silva [UNESP]; Guimaraes, Francisco Silveira; Nunes-De-Souza, Ricardo Luiz [UNESP]; Canto-De-Souza, Azair [UNESP]; Universidade Federal de São Carlos (UFSCar); Universidade Estadual Paulista (UNESP); Neuroscience and Behavioral Institute-INeC; Universidade de São Paulo (USP)
Introduction: Empathy is a fundamental prosocial behavior. It has been defined as perception, awareness, and understanding of others' emotional states, including painful processes. Mice living in pairs with conspecific chronic suffering from constriction injury exhibit pain hypersensitivity mediated by the amygdaloid complex. Nevertheless, the underlying mechanisms in the amygdala responsible for this response remain to be determined. This study investigated if the anxiolytic benzodiazepine midazolam (MDZ) and cannabidiol (CBD), a phytocannabinoid with multiple molecular targets, would attenuate this behavioral change. We also investigated if serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the amygdala are involved in this effect. Materials and Methods: Male Swiss mice were housed in pairs for 28 days. The pairs were divided into two groups on the 14th day: cagemate nerve constriction and cagemate sham. On the 24th day, cagemates underwent a stereotaxic surgery and, on the 28th day, were evaluated on the writhing test. Results: The results showed that living with chronic pain leads to hypernociception in the cagemate and increases the expression of 5-HT3 receptor (5-HT3R) and glutamic acid decarboxylase 67 within the amygdala. MDZ (3.0 and 30 nmol) and CBD (30 and 60 nmol) attenuated the hypernociceptive behavior. The 5-HT3R antagonist ondansetron (0.3 nmol) prevented the antinociceptive effects of MDZ and CBD. Conclusion: These findings indicate that 5-HT3R and GABAergic mechanisms within the amygdala are involved in the pain hypersensitivity induced by the empathy for pain model. They also suggest that MDZ and CBD could be a new potential therapy to alleviate emotional pain disorders.
Electrobiochemical skills of Pseudomonas aeruginosa species that produce pyocyanin or pyoverdine for glycerol oxidation in a microbial fuel cell
(2023-09-01) Zani, Ana Clara Bonizol; Almeida, Érica Janaina Rodrigues de; Furlan, João Pedro Rueda; Pedrino, Matheus; Guazzaroni, María-Eugenia; Stehling, Eliana Guedes; Andrade, Adalgisa Rodrigues de [UNESP]; Reginatto, Valeria; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
Pseudomonas aeruginosa can produce pigments, which mediate external electron transfer (EET). Depending on the mediator, this species can be explored in bioelectrosystems to harvest energy or to obtain chemicals from residual organic compounds. This study has compared the performance of microbial fuel cells (MFCs) inoculated with a Pseudomonas aeruginosa isolate, namely EW603 or EW819, which produce pyocyanin and pyoverdine, respectively. The efficiency of these MFCs in glycerol, a typical residue of biodiesel production, were also compared. The MFCs exhibited different performances. The maximum voltage was 411 and 281 mV m2, the power density was 40.1 and 21.3 mW m−2, and the coulombic efficiency was 5.16 and 1.49% for MFC-EW603 and MFC-EW819, respectively. MFC-EW603 and MFC-EW819 achieved maximum current at 560 and 2200 Ω, at 141.2 and 91.3 mA m−2, respectively. When the system was operated at the respective maximum current output, MFC-EW603 consumed the total glycerol content (11 mmol L−1), and no products could be detected after 50 h. In turn, acetic and butyric acids were detected at the end of MFC-EW819 operation (75 h). The results suggested that P. aeruginosa metabolism can be steered in the MFC to generate current or microbial products depending on the pigment-producing strain and the conditions applied to the system, such as the external resistance. In addition, gene cluster pathways related to phenazine production (phzA and phzB) and other electrogenic-related genes (mexGHI-opmB) were identified in the strain genomes, supporting the findings. These results open new possibilities for using glycerol in bioelectrochemical systems.
Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice
(2023-04-01) da Silva Santos, Yasmin; Gamon, Thais Helena Martins; de Azevedo, Marcela Santiago Pacheco; Telezynski, Bruna Larotonda; de Souza, Edmarcia Elisa; de Oliveira, Danielle Bruna Leal; Dombrowski, Jamille Gregório; Rosa-Fernandes, Livia; Palmisano, Giuseppe; de Moura Carvalho, Leonardo José; Luvizotto, Maria Cecília Rui [UNESP]; Wrenger, Carsten; Covas, Dimas Tadeu; Curi, Rui; Marinho, Claudio Romero Farias; Durigon, Edison Luiz; Epiphanio, Sabrina; Universidade de São Paulo (USP); Oswaldo Cruz Foundation; Hospital Israelita Albert Einstein; Macquarie University; Universidade Estadual Paulista (UNESP); Butantan Institute; Cruzeiro do Sul University
Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.
MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil
(2022-10-25) Castelli, Erick C. [UNESP]; de Castro, Mateus V.; Naslavsky, Michel S.; Scliar, Marilia O.; Silva, Nayane S. B. [UNESP]; Pereira, Raphaela N. [UNESP]; Ciriaco, Viviane A. O. [UNESP]; Castro, Camila F. B. [UNESP]; Mendes-Junior, Celso T.; Silveira, Etiele de S.; de Oliveira, Iuri M.; Antonio, Eduardo C.; Vieira, Gustavo F.; Meyer, Diogo; Nunes, Kelly; Matos, Larissa R. B.; Silva, Monize V. R.; Wang, Jaqueline Y. T.; Esposito, Joyce; Cória, Vivian R.; Magawa, Jhosiene Y.; Santos, Keity S.; Cunha-Neto, Edecio; Kalil, Jorge; Bortolin, Raul H.; Hirata, Mário Hiroyuki; Dell’Aquila, Luiz P.; Razuk-Filho, Alvaro; Batista-Júnior, Pedro B.; Duarte-Neto, Amaro N.; Dolhnikoff, Marisa; Saldiva, Paulo H. N.; Passos-Bueno, Maria Rita; Zatz, Mayana; Universidade Estadual Paulista (UNESP); Universidade de São Paulo (USP); Centro Universitário Sudoeste Paulista; Universidade Federal do Rio Grande do Sul (UFRGS); Universidade La Salle; Instituto Nacional de Ciências e Tecnologia-iii (INCT); Prevent Senior Institute
Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins’ family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
Preparation, cytotoxic activity and DNA interaction studies of new platinum(II) complexes with 1,10-phenanthroline and 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives
(2022-12-01) Souza, Wesley A.; Ramos, Luana M.S.; de Almeida, Angelina M.; Tezuka, Daiane Y.; Lopes, Carla D.; Moreira, Mariete B. [UNESP]; Zanetti, Renan D. [UNESP]; Netto, Adelino V.G. [UNESP]; Ferreira, Francis B.; de Oliveira, Ronaldo Junio; Guedes, Guilherme P.; de Albuquerque, Sérgio; Silva, Júlia R.L.; Pereira-Maia, Elene C.; Resende, Jackson A.L.C.; de Almeida, Mauro V.; Guerra, Wendell; Universidade Federal de Uberlândia (UFU); Universidade Federal de Juiz de Fora; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP); Universidade Estadual de Maringá (UEM); Faculdades Associadas de Uberaba; Universidade Federal do Triângulo Mineiro; Universidade Federal Fluminense (UFF); Universidade Federal de Minas Gerais (UFMG); Universidade Federal do Mato Grosso
This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1)2(1,10-phen)] 1 and [Pt(L2)2(1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with Kb values of 104 M−1. According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism
(2023-05-01) de Jager, Lorena; Vidigal, Camila Borecki; de Campos, Blenda Hyedra; Reginato, Gabriela Souza; Fernandes, Lorena Maria; Ariza, Deborah; Higashi-Mckeown, Carolina Matias; Bertozzi, Mariana Marques; Rasquel de Oliveira, Fernanda Soares; Verri Jr, Waldiceu Aparecido; Ceravolo, Graziela Scalianti; Crestani, Carlos César [UNESP]; Pinge-Filho, Phileno; Martins-Pinge, Marli Cardoso; Universidade Estadual de Londrina (UEL); Universidade Estadual Paulista (UNESP)
Introduction: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. Materials and methods: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (L-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. Results: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. Conclusion: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS.
Flavonoid index and dry matter yield and essential oil of Sphagneticola trilobata (l.) Pruski according to the nitrogen dose and soil type
(2017-01-01) Francisco, D. [UNESP]; Godoy, L. J.G. [UNESP]; Soares, E. V.L. [UNESP]; Moreira, R. R.D. [UNESP]; Universidade Estadual Paulista (UNESP)
The species Sphagneticola trilobata (L) Pruski, a medicinal plant belonging to the Asteraceae family, native to Brazil, is popularly known as pseudo-arnica, margaridão, picão-da-praia or vedelia. Scientific studies have verified the contraceptive, anti-inflammatory, hypoglycemic, antifungal and antibacterial activity against Xanthomonas pelargonii known as bacterial blight, mainly due to the presence of flavonoids. There are reports of larvicidal action against Aedes aegypti that transmits dengue and yellow fever. Yield and essential oil content of flavonoids in plants correlate with stress factors such as low nitrogen availability. The present work aimed to study the influence of nitrogen fertilization on two soil types in which the content of flavonoids and essential oil yield were evaluated. The experimental design was completely randomized 2x5 factorial design, with two soil types, Red-Yellow Latosol and Cambisol, and five N rates (0, 50, 100, 150 and 200), with eight replications. Experimental unit consisted of a vessel containing four stakes with 30 cm of Sphagneticola trilobata. The experiment was conducted in a greenhouse, with the application of nitrogen doses. We concluded that the most appropriate dose of N for the production of dry matter of S. trilobata was 145 mg dm-3 for Cambisol and 136 mg dm-3 for the Red-Yellow Latosol. The absence of N promoted the highest rate of flavonoids in both soils. The most appropriate dose of N to the highest oil yield was 108 mg dm-3 for Cambisol.
Cordia verbenacea DC. (Boraginaceae): quality control parameters, phytochemical screening and evaluation of anti-Candida activity
(2016-01-01) Scardelato, J. A. [UNESP]; Santos, A. G. [UNESP]; Pietro, R. C.L.R. [UNESP]; Sacramento, L. V.S. [UNESP]; Universidade Estadual Paulista (UNESP)
Cordia verbenacea occurs all along the Brazilian coast and it is widely used to treat various inflammatory processes. In the present study we aimed to describe a physical-chemical profile and pharmacognostic vegetal drug as well as to draw a chromatographic profile of the crude extract and its fractions. We have observed the occurrence of secondary metabolites such as flavonoids, terpenes and tannins. The study of anti-Candida activity of extracts indicated the best results for C. glabrata (9.77-36.06 μg.mL-1), intermediate values for C. krusei (312.5-625 μg.mL-1), C. tropicalis (312.5-625μg.mL-1) and high values for C. albicans (1250>2500 μg.mL-1) and C. parapsilosis 625-2500 μg.mL-1).
Pharmacokinetic Profile of Metformin and SGLT2 Inhibitors alone and in Combination: a Pharmacokinetic Study in Wistar Rats
(2023-01-01) Fachi, Mariana Millan; Dias, Bruna Carolina Lui; de Oliveria, Jonata Augusto [UNESP]; Peccinini, Rosângela Gonçalves [UNESP]; Pontarolo, Roberto; de Campos, Michel Leandro; Universidade Federal do Paraná (UFPR); Universidade Estadual Paulista (UNESP); Federal University of Mato Grosso (UFMT)
Objective: To achieve glycemic control, a combination of drugs is eventually necessary, especially the dual therapy of SGLT2 inhibitors with metformin. Despite the value of combination therapy, understanding the pharmacokinetic properties is critical. Therefore, this study aimed to conduct the combined and isolated administration of hypoglycemic drugs to understand their pharmacokinetic properties. Methodology: The study was performed by gavage in twenty-five rats that were divided into five groups: metformin alone (60 mg/ kg), canagliflozin alone 20 mg/kg, canagliflozin and metformin (20 mg/kg and 60 mg/kg, respectively), dapagliflozin alone 2 mg/kg, and dapagliflozin and metformin (2 mg/kg and 60 mg/kg, respectively). Blood samples were collected between 0.25 and 36 hours postdose and quantified by an HPLC-MS/MS method. Results: The metformin pharmacokinetics showed values lower than those from literature, but the most relevant result was a significant change in Cmax (3400 ng/mL), AUC (872.4 ng.min/L) and CL/F (72 mL/min/kg) in the metformin with dapagliflozin group compared to metformin alone Cmax (523 ng/mL), AUC (106.8 ng.min/L) and CL/F (752 mL/min/kg). For canagliflozin, the Cmax of 6116.7 ng/mL observed in our study was similar to that observed in literature, while the clearance (5.1 mL/min/kg) was higher than that of literature, which was 3.5 mL/min/kg. Clearance of dapagliflozin CL/F was reported as 3.33 mL/min/kg, while our result was 4.6 mL/ min/kg. The same study also published dapagliflozin half-life and MRT, which were slightly lower than our findings. In general, the parameters of canagliflozin and dapagliflozin were similar to the literature and did not change with simultaneous administration with metformin. Conclusion: Dapagliflozin significantly changed the pharmacokinetic disposition of metformin, while metformin coadministration had no influence on the pharmacokinetics of SGLT2 inhibitors.
Recycled Household Ash in Rice Paddies of Bangladesh for Sustainable Production of Rice Without Altering Grain Arsenic and Cadmium
(2023-01-01) Gupta, Yogesh; Hossain, Mahmud; Islam, M. Rafiqul; Talukder, Md. Moyeed Hasan; Khokon, Md. Atiqur Rahman; Uddin, Mohammad Mahir; Kabir, Humayun; Carey, Manus; Ralphs, Kathryn; de Moraes, Natalia Valadares [UNESP]; Meharg, Andrew A.; Meharg, Caroline; Queen’s University Belfast; Bangladesh Agricultural University; Universidade Estadual Paulista (UNESP)
In Bangladesh most agronomic biomass (straw, husk, dried dung) is burnt for domestic cooking use. Consequently, the soil is continuously stripped of mineral nutrients and carbon (C) substrate. QueryHere we investigate if recycling of household ash (ash) as fertilizer can sustainably improve soil fertility as well as minimise accumulation of toxic elements (As, Cd) in rice grain. Large scale field trials across two geographic regions (Barind, Madhupur) and two seasons (wet, dry) and with application of 3 fertiliser treatments (NPKS, ash, NPKS + ash) were conducted. At the end of each season, the impact of region*season*treatment on soil microbial comunities, rice yield, and grain quality (As, Cd, nutrient elements) was assessed. When compared to conventional field application rates of NPKS (control), application of ash boosted rice yield by circa. 20% in both regions during wet and dry season, with no effect on rice grain carcinogenic inorganic arsenic (iAs), dimethylarsonic acid (DMA) or cadmium (Cd), but with potential to increase zinc (Zn). For soil microbial communities, a significant region and season effect as well as correlation with elements in rice grain was observed, amongst these Cd, Zn, iAs and DMA. This study illustrates that application of ash can reduce the requirement for expensive chemical fertiliser, whilst at the same time increasing rice yield and maintaining grain quality, making farming in Bangladesh more sustainable and productive. The study also implies that the combined impact of region, season, and soil microbes determines accumulation of elements in rice grain.
Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol
(2022-01-01) Franchin, Taísa Busaranho [UNESP]; de Oliveira, Jonata Augusto [UNESP]; Candido, Caroline Damico [UNESP]; Martins, Evelin Dos Santos [UNESP]; Padilha, Elias Carvalho [UNESP]; de Campos, Michel Leandro [UNESP]; Peccinini, Rosângela Gonçalves [UNESP]; Universidade Estadual Paulista (UNESP); Federal University of Mato Grosso
Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.
Evaluation of cytotoxicity and genotoxicity of a novel oxovanadium complex with orotate
(2022-11-01) da Silva Gomes, Pietra Stefany; da Silva, Washington Wilson; de Cássia Gasparoti, Gabriela; Payolla, Filipe Boccato; de Oliveira, Jonata Augusto [UNESP]; Barbugli, Paula Aboud [UNESP]; Marin-Dett, Freddy Humberto [UNESP]; Cavicchioli, Maurício; Massabni, Antonio Carlos; Resende, Flávia Aparecida; UNIARA – University of Araraquara; Universidade Estadual Paulista (UNESP)
The development of new drugs based on metal complexes requires a detailed analysis of their biological endpoints. In this study, we report the genotoxic profile and influence on cell proliferation and death of the oxovanadium(IV) complex with orotic acid ([VO(C5H4N2O4)2], VO(oro)). Human hepatocellular carcinoma cells (HepG2) were the most sensitive tumor cells to VO(oro), which interfered with the integrity of cell membranes and proliferative capacity in a dose-dependent manner, inducing cell death by apoptosis. Regarding genotoxicity, VO(oro) did not induce considerable levels of DNA damage in HepG2 cells (comet test) and gene mutations (Ames test). However, it caused a statistically significant increase in the frequency of micronuclei at the highest concentration tested (12.5 µmol.L–1), indicating aneuploidy and clastogenicity. The data presented here provide information on various biological aspects of the VO(oro) complex, which may allow the elucidation of its mechanism of action as a possible therapeutic agent.
Cannabidiol Treatment Shows Therapeutic Efficacy in a Rodent Model of Social Transfer of Pain in Pair-Housed Male Mice
(Mary Ann Liebert, Inc, 2023-04-18) Tavares, Ligia Renata Rodrigues [UNESP]; Petrilli, Leonardo Abdelnur; Baptista-de-Souza, Daniela [UNESP]; Canto-de-Souza, Lucas [UNESP]; Planeta, Cleopatra da Silva [UNESP]; Guimaraes, Francisco Silveira; Nunes-de-Souza, Ricardo Luiz [UNESP]; Canto-de-Souza, Azair [UNESP]; Universidade Federal de São Carlos (UFSCar); Universidade Estadual Paulista (UNESP); Neurosci & Behav Inst IneC; Universidade de São Paulo (USP)
Introduction: Prosocial behavior refers to sharing emotions and sensations such as pain. Accumulated data indicate that cannabidiol (CBD), a nonpsychotomimetic component of the Cannabis sativa plant, attenuates hyperalgesia, anxiety, and anhedonic-like behavior. Nevertheless, the role of CBD in the social transfer of pain has never been evaluated. In this study, we investigated the effects of acute systemic administration of CBD in mice that cohabited with a conspecific animal suffering from chronic constriction injury. Furthermore, we assessed whether repeated CBD treatment decreases hypernociception, anxiety-like behavior, and anhedonic-like responses in mice undergoing chronic constriction injury and whether this attenuation would be socially transferred to the partner.Materials and Methods: Male Swiss mice were Housed in pairs for 28 days. On the 14th day of living together, animals were then divided into two groups: cagemate nerve constriction (CNC), in which one animal of each partner was subjected to sciatic nerve constriction; and cagemate sham (CS), subjected to the same surgical procedure but without suffering nerve constriction. In Experiments 1, 2, and 3 on day 28 of living together, the cagemates (CNC and CS) animals received a single systemic injection (intraperitoneally) of vehicle or CBD (0.3, 1, 10, or 30 mg/kg). After 30 min, the cagemates were subjected to the elevated plusmaze followed by exposure to the writhing and sucrose splash tests. For chronic treatment (Exp. 4), sham and chronic constriction injury animals received a repeated systemic injection (subcutaneous) of vehicle or CBD (10 mg/kg) for 14 days after the sciatic nerve constriction procedure. On days 28 and 29 sham and chronic constriction injury animals and their cagemates were behaviorally tested.Results and Conclusion: Acute CBD administration attenuated anxiety-like behavior, pain hypersensitivity, and anhedonic-like behavior in cagemates that cohabited with a pair in chronic pain. In addition, repeated CBD treatment reversed the anxiety-like behavior induced by chronic pain and enhanced the mechanical withdrawal thresholds in Von Frey filaments and the grooming time in the sucrose splash test. Moreover, repeated CBD treatment effects were socially transferred to the chronic constriction injury cagemates.
Myotoxin Inhibitors
(Springer, 2017-01-01) Santos-Filho, Norival Alves [UNESP]; Silveira, Lucas Blundi; Boldrini-Franca, Johara; Cruz, L. J.; Luo, S.; Gopalakrishnakone, P.; Universidade Estadual Paulista (UNESP); Universidade de São Paulo (USP)
Myonecrosis is an important medical complication in snake envenoming and, in severe cases, can lead to drastic sequelae, such as inability and permanent tissue loss. Although the traditional serum therapy effectively neutralizes the systemic effects induced by snake venoms, there are some limitations in reversing the local symptoms induced by myotoxins, since they are small- and medium-sized proteins of low immunogenicity. Due to this impairment in current snakebite treatment, there has been an increasing interest in the search for naturally occurring molecules, as well as in the design of synthetic compounds, which are able to inhibit the main pathophysiological effects induced by snake venom PLA(2) and other myotoxins. These inhibitory molecules are mainly obtained from animal blood and plant extracts; however, a diversity of other sources of myotoxin inhibitors has also been described. This chapter aims to provide current information regarding the diversity of natural and synthetic PLA(2) inhibitors described so far. Moreover, a better understanding of the mechanisms of action involved in PLA(2) inhibition may generate perspectives to the use of these molecules leading to the development of novel therapeutic approaches for snakebite management.
Jaboticaba (Myrciaria cauliflora (Mart.) O.Berg. [Myrtaceae])
(Woodhead Publ Ltd, 2011-01-01) Almeida Teixeira, G. H. de; Berlingieri Durigan, M. F.; Durigan, J. F. [UNESP]; Yahia, E. M.; Universidade de São Paulo (USP); Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA); Universidade Estadual Paulista (UNESP)
Jaboticaba is a small tree, native to the central-south of Brazil. Among the well-known species the most important are the Myrciaria cauliflora (DC) Berg and the Myrciaria jaboticaba (Vell) Berg which produce adequate fruit for both industry (jams, preserves, liqueur and wine) and fresh consumption. This chapter presents the origin, botany, morphology, structure, nutritional value and health benefits of this fruit. It then reviews its postharvest physiology, maturity and quality components, as well as preharvest and postharvest factors which affect fruit quality, problems with physiological and pathological disorders and pests. It also discusses postharvest handling practices and processing.
Toxicity Assessment Methods and Protocols Preface
(Humana Press Inc, 2021-01-01) Marques Palmeira, Carlos Manuel; Oliveira, Danielle Palma de [UNESP]; Dorta, Daniel Junqueira [UNESP]; Palmeira, CMM; DeOliveira, D. P.; Dorta, D. J.; Univ Coimbra; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
Electrochemical Methods for Environmental Remediation
(Royal Soc Chemistry, 2020-01-01) Guzman, Paola Villegas; Martinez-Huitle, Carlos A. [UNESP]; Hussain, C. M.; Univ Fed Rio Grande do Norte; Universidade Estadual Paulista (UNESP)
Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients
(2022-07-22) Teixeira, Silvia A.; Burim, Regislaine V.; Viapiano, Mariano S.; Bidinotto, Lucas T. [UNESP]; Nagashi Marie, Suely K.; Fleury Malheiros, Suzana M.; Oba-Shinjo, Sueli M.; Andrade, Augusto F.; Carlotti, Carlos G.; Universidade de São Paulo (USP); Barretos Cancer Hospital; Brigham and Women’s Hospital and Harvard Medical School; SUNY Upstate Medical University; Universidade Estadual Paulista (UNESP); Barretos School of Health Sciences; McGill University
Integrins are heterodimeric transmembrane glycoproteins resulting from the non-covalent association of an α and β chain. The major integrin receptor for collagen/laminin, α2β1 is expressed on a wide variety of cell types and plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Integrin-triggered signaling pathways promote the invasion and survival of glioma cells by modifying the brain microenvironment. In this study, we investigated the association of a specific genetic polymorphism of integrin α2β1 with the incidence of diffusely infiltrating astrocytoma and the progression of these tumors. Single-nucleotide polymorphism in intron 7 of the integrin ITGA2 gene was examined in 158 patients and 162 controls using polymerase chain reaction and restriction enzyme analysis. The ITGA2 genotype +/+ (with a BglII restriction site in both alleles) exhibited higher frequency in grade II astrocytoma compared to control (P = 0.02) whereas the genotype -/- (lacking the BglII site) correlated with the poorest survival rate (P = 0.04). In addition, in silico analyses of ITGA2 expression from low-grade gliomas (LGG, n = 515) and glioblastomas (GBM, n = 159) indicated that the higher expression of ITGA2 in LGG was associated with poor overall survival (P < 0.0001). However, the distribution of integrin ITGA2 BglII genotypes (+/+, +/-, -/-) was not significantly different between astrocytoma subgroups III and IV (P = 0.65, 0.24 and 0.33; 0.29, 0.48, 0.25, respectively) compared to control. These results suggest a narrow association between the presence of this SNP and indicate that further studies with larger samples are warranted to analyze the relation between tumor grade and overall survival, highlighting the importance of determining these polymorphisms for prognosis of astrocytomas.
Time-related multivariate strategy for the comprehensive evaluation of microbial chemical data
(2022-06-01) Selegato, Denise M. [UNESP]; Freitas, Thamires R.; Pivatto, Marcos; Pivatto, Amanda D.; Pilon, Alan C.; Castro-Gamboa, Ian [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal de Uberlândia (UFU); Universidade de São Paulo (USP); European Molecular Biology Laboratory (EMBL)
Introduction: In microbial metabolomics, the use of multivariate data analysis (MDVA) has not been comprehensively explored regarding the different techniques available and the information that each gives about the metabolome. To overcome these limitations, here we show the use of Fusarium oxysporum cultured in the presence of exogenous alkaloids as a model system to demonstrate a comprehensive strategy for metabolic profiling. Matherials and methods: F. oxysporum was harvested on different days of incubation after alkaloidal addition, and the chemical profiles were compared using LC–MS data and MDVA. We show significant innovation to evaluate the chemical production of microbes during their life cycle by utilizing the full capabilities of Partial Least Square (PLS) with microbial-specific modeling that considers incubation days, media culture availability, and growth rate in solid media. Results and Discusscion: Results showed that the treatment of the Y-data and the use of both PLS regression and discrimination (PLSr and PLS-DA) inferred complemental chemical information. PLSr revealed the metabolites that are produced/consumed during fungal growth, whereas PLS-DA focused on metabolites that are only consumed/produced at a specific period. Both regression and classificatory analysis were equally important to identify compounds that are regulated and/or selectively produced as a response to the presence of the alkaloids. Lastly, we report the annotation of analogs from the piperidine alkaloids biotransformed by F. oxysporum as a defense response to the toxic plant metabolites. These molecules do not show the antimicrobial potential of their precursors in the fungal extracts and were rapidly produced and consumed within 4 days of microbial growth.

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