Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet / Efeitos da ingestão do herbicida glifosato na função renal de ratos em uma dieta balanceada

Abstract Introduction: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Methods: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. Results: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. Conclusion: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

RESUMO Introdução: O glifosato é o herbicida mais utilizado no mundo e no Brasil. Atualmente, há uma preocupação crescente com os efeitos do glifosato na saúde humana. O Instituto Brasileiro de Defesa do Consumidor apresentou dados sobre a presença de glifosato em alguns dos produtos ultraprocessados mais consumidos no Brasil. Atualmente, as regulamentações sobre o limite máximo desses resíduos em alimentos ultraprocessados ainda não foram estabelecidas pela Vigilância Sanitária Nacional, e o consumo de alimentos ultraprocessados está indepen­dentemente associado a um risco maior de doença renal crônica incidente. Métodos: Como uma dieta desbalanceada pode interferir na função renal, este estudo tem como objetivo investigar o efeito da ingestão diária de 5 mg/kg pc de glifosato em conjunto com uma dieta equilibrada e o possível impacto na função renal em ratos. Foram avaliados função renal, peso dos rins, marcadores de lesão renal e estresse oxidativo. Resultados: Houve redução no peso dos rins. As principais alterações histopatológicas nos tecidos renais foram vacuolização no estágio inicial e regulação positiva do marcador de lesão renal KIM-1. A lesão renal está associada à produção aumentada de espécies reativas de oxigênio nas mitocôndrias. Conclusão: Esse estudo mostrou alterações nos rins de ratos expostos a uma dieta balanceada com glifosato, sugerindo um risco potencial ao rim humano. Presumivelmente, alimentos ultraprocessados que contenham glifosato podem potencializar esse risco. A relevância desses resultados está no fato de chamar a atenção para a necessidade de regulamentar a concentração de glifosato em alimentos ultraprocessados no futuro.

Does a therapeutical dose of ivermectin impairs testicular homeostasis of rats via excessive apoptosis?

Ivermectin is a medication used to treat parasite infestations in humans and in veterinary medicine. Previously we showed that therapeutical doses of ivermectin impaired spermatogenesis and spermiogenesis in adult rats. The present study was proposed to understand the pathophysiological mechanism that triggered these impairments induced by ivermectin. It was a particular objective to study if ivermectin induced excessive apoptosis. Adult rats were treated with a therapeutical dose of ivermectin (subcutaneously). Their testis was evaluated for the expression of caspase-3 (a marker of apoptosis), using immunohistochemistry techniques. Results revealed that ivermectin treatment increased the expression of caspase-3 (labeled seminiferous tubules and strongly labeled tubules), as well as increased the number of tubules that presented labeled cells in the tubular lumen, compared to the data of the control group. In conclusion, a therapeutical dose of ivermectin induced expressive apoptosis in cells of the seminiferous tubules of rats, affecting the testicular natural homeostasis process, which resulted in the spermatogenesis and spermiogenesis impairments previously reported.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet.

INTRODUCTION: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. METHODS: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. RESULTS: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. CONCLUSION: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

The Nephroprotective Effects of the Allogeneic Transplantation with Mesenchymal Stromal Cells Were Potentiated by ω3 Stimulating Up-Regulation of the PPAR-γ.

Mesenchymal stromal cells (MSCs) obtained from bone marrow are a promising tool for regenerative medicine, including kidney diseases. A step forward in MSCs studies is cellular conditioning through specific minerals and vitamins. The Omega-3 fatty acids (ω3) are essential in regulating MSCs self-renewal, cell cycle, and survival. The ω3 could act as a ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ). This study aimed to demonstrate that ω3 supplementation in rats could lead to the up-regulation of PPAR-γ in the MSCs. The next step was to compare the effects of these MSCs through allogeneic transplantation in rats subjected to unilateral ureteral obstruction (UUO). Independent of ω3 supplementation in the diet of the rats, the MSCs in vitro conserved differentiation capability and phenotypic characteristics. Nevertheless, MSCs obtained from the rats supplemented with ω3 stimulated an increase in the expression of PPAR-γ. After allogeneic transplantation in rats subjected to UUO, the ω3 supplementation in the rats enhanced some nephroprotective effects of the MSCs through a higher expression of antioxidant enzyme (SOD-1), anti-inflammatory marker (IL-10), and lower expression of the inflammatory marker (IL-6), and proteinuria.

MicroRNA biogenesis machinery activation and lncRNA and REST overexpression as neuroprotective responses to fight inflammation in the hippocampus.

Brain Long non-coding RNA (lncRNA) and microRNAs (miRs) play essential roles in the regulation of several important biological processes, including neuronal activity, cognitive processes, neurogenesis, angiogenesis, and neuroinflammation. In this context, the transcriptional repressor, RE1 silencing transcription factor (Rest), acts regulating the expression of neuronal genes as well as of lncRNAs and multiple miRNAs in the central nervous system. Nevertheless, its role in neuroinflammation was less explored. Here, we demonstrate, using an in vivo model of neuroinflammation induced by i.p. injection of LPS (0.33 mg/kg), that neuroinflammation increases gene expression of pro-inflammatory cytokines concomitant with the native and truncated forms of Rest and of non-coding RNAs. Additionally, the increased expression of enzymes Drosha ribonuclease III) (Drosha), Exportin 5 (Xpo5) and Endoribonuclease dicer (Dicer), associated with high expression of neuroprotective miRs 22 and 132 are indicative that the activation of biogenesis of miRs in the hippocampal region is a Central Nervous System (CNS) protective mechanism for the deleterious effects of neuroinflammation. Our results indicate that positive regulation of Rest gene expression in the hippocampal region by neuroinflammation correlates directly with the expression of miRs 22 and 132 and inversely with miR 335. In parallel, the confirmation of the possible alignment between the lncRNAs with miR 335 by bioinformatics corroborates with the sponge effect of Hottip and Hotair hybridizing and inhibiting the pro-inflammatory action of miR 335. This suggests the existence of a possible correlation between the activation of miR biogenesis machinery with increased expression of the transcription factor Rest, contributing to neuroprotection.

Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem.

Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg-1·day-1 PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7-31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.

Progressive tremor and motor impairment in seizure-prone mutant tremor mice are associated with neurotransmitter dysfunction.

BACKGROUND: The tremor mutant mice present motor impairments comprised of whole-body tremors, ataxia, decreased exploratory behavior, and audiogenic seizures. OBJECTIVES: This study aims to investigate the development of motor dysfunction in this mutant mouse and the relationships with cortical, striatal, and cerebellar levels of GABA, glutamate, glycine, dopamine (DA), serotonin (5-HT), noradrenaline (NOR), and its metabolites. The serum cytokines levels, myelin content, and the astrocytic expression of the glial fibrillary acidic protein (GFAP) investigated the possible influence of inflammation in motor dysfunction. RESULTS: Relative to wild-type (WT) mice, the tremor mice presented: increased tremors and bradykinesia associated with postural instability, decreased range of motion, and difficulty in initiating voluntary movements directly proportional to age; reduced step length for right and left hindlimbs; reduced cortical GABA, glutamate and, aspartate levels, the DOPAC/DA and ratio and increased the NOR levels; in the striatum, the levels of glycine and aspartate were reduced while the HVA levels, the HVA/DA and 5HIAA/5-HT ratios increased; in the cerebellum the glycine, NOR and 5-HIAA levels increased. CONCLUSIONS: We suggest that the motor disturbances resulted mainly from the activation of the indirect striatal inhibitory pathway to the frontal cortex mediated by GABA, glutamate, and aspartate, reducing the dopaminergic activity at the prefrontal cortex, which was associated with the progressive tremor. The reduced striatal and increased cerebellar glycine levels could be partially responsible for the mutant tremor motor disturbances.

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

The recessive mutant mouse bate palmas (bapa) arose from N-ethyl-N-nitrosourea mutagenesis. Previous studies of our group revealed some behavioral impairments and a mutation in the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. Because mutations in the KMT2D gene in humans are mainly responsible for Kabuki syndrome, this study was proposed to validate bapa mice as a model of Kabuki syndrome. Besides other symptoms, Kabuki syndrome is characterized by increased susceptibility to infections and speech impairments, usually diagnosed in the early childhood. Thus, juvenile male and female bapa mice were studied in different developmental stages (prepubertal period and puberty). To induce sickness behavior and to study infection susceptibility responses, lipopolysaccharide (LPS) was used. To study oral communication, ultrasonic vocalizations were evaluated. Behavioral (open-field test) and central (astrocytic glial fibrillary acidic protein [GFAP] and tyrosine hydroxylase [TH]) evaluations were also performed. Control and bapa female mice emitted 31-kHz ultrasounds on prepubertal period when exploring a novel environment, a frequency not yet described for mice, being defined as 31-kHz exploratory vocalizations. Males, LPS, and puberty inhibited these vocalizations. Bapa mice presented increased motor/exploratory behaviors on prepubertal period due to increased striatal TH expression, revealing striatal dopaminergic system hyperactivity. Combining open-field behavior and GFAP expression, bapa mice did not develop LPS tolerance, that is, they remained expressing signs of sickness behavior after LPS challenge, being more susceptible to infectious/inflammatory processes. It was concluded that bapa mice is a robust experimental model of Kabuki syndrome.

Luffa operculata at a late period of gestation dysregulates melatonin and cytokines interfering with weight of dams and their male offspring.

ETHNOPHARMACOLOGICAL RELEVANCE: The tea made with the fruits of Luffa operculata (L.) Cogn. (Cucurbitaceae; EBN) is popularly used as abortive. AIM OF THE STUDY: The present work aimed at accessing how the exposition of female Wistar rats to 1.0 mg/kg of EBN (experimental group, EG), or distilled water (control group, CG), by gavage, at gestational days (GD) 17-21 interfered with the reproductive performance, and with dams' behavior after weaning. MATERIALS AND METHODS: At post-natal day 2 (PND2), the number of male and female pups was evaluated, as well as their weight. After weaning (PND21), dams were euthanized, and their liver and kidneys were removed for histological and biochemical analyses, while the blood was used in the evaluation of cytokines IL-1α, IL-1ß, IL-6 and TNF-α, corticosterone, adrenocorticotrophic hormone, melatonin, AST, ALT and creatinine levels. RESULTS AND DISCUSSION: Dams that were treated with EBN showed an anxiety-like behavior, weight loss at the end of gestation and weight gain at weaning, accompanied with a significant decrease in pro-inflammatory cytokines and in the melatonin level. No significant histological or biochemical alterations have occurred in the liver or kidneys. The number of female pups was significantly higher in the EG. The male pups showed weight gain at PND60. CONCLUSION: The presence of cucurbitacins is probably involved in the dysregulations that were found, due to their polycyclic steroid triterpene structure.

Vertical exposition to Luffa operculata extract deregulates behavior and hypothalamus neurotransmitters in juvenile rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Luffa operculata (L.) Cogn (Cucurbitaceae) is a traditional plant popularly used in the abortion induction, against sinusitis and is toxic. AIM OF THE STUDY: To verify the influence of the aqueous extract obtained from the dry fruit of L. operculata (BNE) on the male rats vertically exposed to a subabortive dose of BNE, by evaluating alterations in behavior and neurochemical features in hypothalamus, striatum and frontal cortex, at a juvenile age, after receiving a stress challenge given by the use of the "New York subway stress" technique (NYS). MATERIALS AND METHODS: Pregnant female rats (F0 generation) received 1.0 mg/kg BNE, or distilled water (100 mL/kg), by gavage, between gestation days GD17 and GD21. The pups were weaned at PND21 and were kept up to PND60 (juvenile age) in controlled environmental conditions. Four groups were obtained: control (CG), experimental (EG), stress control (SCG) and stress experimental (SEG) After being stressed, the animals were behavioral screened for in the open field (OF) and in light-dark box (LDB) apparatuses. They were euthanized, and the liver, kidneys and brain were removed for both macroscopic and microscopic analyses, and for quantification of vanillylmandelic acid (VMA), norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the serotonin (5-HT) and its metabolite 5-hydroxyindolylacetic acid (5-HIAA) were accessed in the hypothalamus, frontal cortex and striatum. RESULTS AND DISCUSSION: although most of the behavior changes were due to the stress challenge, the rats spent more time in the dark side of the LDB and were less likely to explore the light side, indicating that the treatment with BNE induced to fear. Interferences of BNE over behavior were due to impairment of VMA, NE, 5-HT and DA and increasing of DOPAC in the hypothalamus, and an increase of 5-HIAA in the frontal cortex, indicating alterations in the hypothalamic-hypophysis-adrenal axis (HHAA). No macroscopic or histopathological changes were observed in the liver, kidneys, or brain, although GFAP was diminished in the SCG, as expected for stressed rats. CONCLUSION: the vertical exposition of juvenile rats to BNE led to the manifestation of fear and to a down regulation of the hypothalamic-hypophysis-adrenal axis.

Zinc, but not paracetamol, prevents depressive-like behavior and sickness behavior, and inhibits interferon-gamma and astrogliosis in rats.

Considering all mental and addictive disorders, depression is the most responsible for years of life lost due to premature mortality and disability. Antidepressant drugs have limited effectiveness. Depression can be triggered by immune/inflammatory factors. Zinc and paracetamol interfere with immune system and have demonstrated beneficial effects on depression treatment when administered concomitant with antidepressant drugs. The objective of this study was to test zinc and/or paracetamol as treatments of depressive-like behavior, sickness behavior, and anxiety in rats, as well as to understand the central and peripheral mechanisms involved. Sickness behavior and depressive-like behavior were induced in rats with repetitive lipopolysaccharide (LPS, 1 mg/kg for two consecutive days) administrations. Rats received zinc and/or paracetamol for three consecutive days. Sickness behavior (daily body weight and open field general activity); anxiety (light-dark test); depressive-like/antidepressant behavior (forced swim test); plasma corticosterone and interferon (IFN)-gamma levels; and glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) brain expression were evaluated. LPS induced sickness behavior and depressive-like behavior, as well as elevated IFN-gamma levels and increased GFAP expression. Zinc prevented both behavioral and biochemical impairments. Paracetamol and zinc + paracetamol association induced only slight beneficial effects. Anxiety, corticosterone, and TH do not seem be related with depression and the other behavioral and neuroimmune changes. In conclusion, zinc treatment was beneficial for sickness behavior and depressive-like behavior without concomitant administration of antidepressants. IFN-gamma and GFAP were linked with the expression of sickness behavior and depressive-like behavior and were also involved with the antidepressant effects. Therefore, zinc, IFN-gamma, and GFAP pathways should be considered for depression treatment.

Chemobrain in rats: Behavioral, morphological, oxidative and inflammatory effects of doxorubicin administration.

Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). The present study investigated whether DOX administration could affect behavior and brain morphology, as well as oxidative and inflammatory status in rats. Male Wistar rats were injected with DOX (2.5 mg/kg/week, 4 weeks, i.p.) or saline. Behavioral analyses were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry (for glial fibrillary acidic protein expression in astrocytes; GFAP). Serum and brain levels of TNF-α, IL-1ß, IL-6, IL-8, IL-10 and CXCL-1 were determined. Oxidative parameters, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), nitric oxide (NO•), brain iron and ferritin levels, as well as reduced and oxidized glutathione (GSH and GSSG, respectively) and thiobarbituric acid reactive substances (TBARS) were also assessed in brain. DOX-injected rats presented cognitive/memory impairments, increased GFAP expression, increased levels of TBARS, NO and GR, but decreased GSSG and ferritin levels in brain homogenate. In addition, increased serum and brain levels of IL-6, IL-8 and CXCL1 were noted in the DOX group, although IL-10 decreased. As DOX has a poor penetration across the blood-brain barrier (BBB), it is proposed that this drug elicits a systemic proinflammatory response with increase of proinflammatory cytokines which cross the BBB and can be involved in the induction of oxidative molecules and proinflammatory cytokines that altogether induce astrogliosis all over the brain. These events may be responsable for chemotherapy-induced cognitive/memory deficits.

Reduced astrocytic expression of GFAP in the offspring of female rats that received hypercaloric diet.

Introduction: Obesity promotes hypothalamic inflammation and local morphological changes in astrocytes, including the increased expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP), which is seen as a sign of neuroinflammation.Objective: This study aimed to observe the astrocytic expression of GFAP in different brain areas from female rats that received a hypercaloric (HD) or a normocaloric (ND) diet during puberty (F0 generation) as well as in their male pups (F1 generation).Methods: Female rats received highly palatable HD (Ensure®) or ND from postnatal day (PND) 23-65. On PND90-95, some were euthanized for the immunohistochemical study and some were mated to obtain the F1 generation. Male pups were immunochallenged on PND50 with lipopolysaccharide (LPS, 100 µg/kg) or 0.9% saline solution (1 mL/kg) intraperitoneal injection. Body weight (BW) and retroperitoneal fat weight (RFW) were recorded on PND95 for F0 generation and on PND50 for F1 generation. GFAP expression for both generations was assessed by morphometry in the parietal/frontal cortex, corpus callosum, nucleus accumbens, arcuate/periventricular nuclei of hypothalamus, pons, molecular/granular layers of cerebellum.Results: Female rats fed with HD presented a significant increase in the GFAP expression in all evaluated areas as well as in the RFW. Male rats born from mothers that received HD showed decreased GFAP expression, BW and RFW when treated with LPS in relation to those from mothers fed with ND.Discussion: HD induced astrogliosis in several brain areas in females from F0 generation and an adaptive phenotypic change of decreased GFAP expression in males from F1 generation after LPS challenge.

Dioclea violacea lectin modulates the gentamicin activity against multi-resistant strains and induces nefroprotection during antibiotic exposure.

Gentamicin is an aminoglycoside antibiotic used to treat infections of various origins. In the last few decades, the constant use of gentamicin has resulted in increased bacterial resistance and nephrotoxicity in some cases. In this study, we examined the ability of Dioclea violacea lectin (DVL) in modulate the antimicrobial activity of gentamicin and reduce the nephrotoxicity induced by this drug. The minimum inhibitory concentration (MIC) obtained for DVL against all strains studied was not clinically relevant (MIC ≥ 1024 µg/mL). However, when DVL was combined with gentamicin, a significant increase in antibiotic action was observed against Staphylococcus aureus and Escherichia coli. DVL also reduced antibiotic tolerance in S. aureus during 10 days of continuous treatment. In addition, DVL presented a nephroprotective effect, reducing sodium excretion, N-Gal expression and urinary protein, that are important markers of glomerular and tubular injuries. Taken together, studies of inhibition of hemagglutinating activity, fluorescence spectroscopy and molecular docking revealed that gentamicin can interact with DVL via the carbohydrate recognition domain (CRD), suggesting that the results obtained in this study may be directly related to the interaction of DVL-gentamicin and with the ability of the lectin to interact with glycans present in the cells of the peritoneum.

Memory impairments and increased GFAP expression in hippocampal astrocytes following hypercaloric diet in rats.

OBJECTIVE: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. METHODS: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. RESULTS: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. CONCLUSION: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.

Memory impairments and increased GFAP expression in hippocampal astrocytes following hypercaloric diet in rats / Prejuízos de memória e expressão aumentada de GFAP em astrócitos hipocampais após dieta hipercalórica em ratos

ABSTRACT Objective: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. Methods: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. Results: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. Conclusion: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.

RESUMO Objetivo: A inflamação hipotalâmica e a superexpressão da proteína glial fibrilar ácida (GFAP) em astrócitos são bem descritas em animais obesos, assim como déficits cognitivos e de memória. Como o hipocampo desempenha importante papel na consolidação de informações, esta investigação teve como objetivo observar a função da memória e a expressão astrocitária da GFAP no hipocampo de ratos que receberam dieta hipercalórica ou normocalórica. Métodos: Ratos Wistar machos adultos receberam dieta rica em gordura (cafeteria) ou dieta padrão por 60 dias. No 61º dia, os ratos foram submetidos ao teste de reconhecimento de objetos (NOR) 3 e 24 horas após o primeiro contato com os objetos, para avaliação da memória de curto e de longo prazo, respectivamente. Após, os ratos foram eutanasiados e os encéfalos coletados para pesquisa imuno-histoquímica da expressão astrocitária de GFAP no hipocampo (áreas CA1, CA2 e CA3) e no hipotálamo (núcleos periventricular e arqueado). A reatividade astrocitária foi avaliada por morfometria. Diferentes depósitos de tecido adiposo branco e marrom foram pesados para calcular o índice de adiposidade. Resultados: A dieta hipercalórica aumentou o ganho de peso corporal, o índice de adiposidade, o peso do tecido adiposo branco (epididimal, subcutâneo e retroperitoneal) e marrom. Ratos alimentados com dieta hipercalórica apresentaram prejuízos na memória de curto e longo prazo no teste NOR e aumento da expressão de GFAP em astrócitos de todas as áreas hipotalâmicas e hipocampais analisadas. Conclusão: Esta astrogliose sugere que a resposta neuroinflamatória também ocorre no hipocampo, podendo estar envolvida nas perdas de memória observadas em animais obesos/com sobrepeso.

Evaluation of lumbar endoscopic discectomy in obese patients / Avaliação da discectomia lombar endoscópica em pacientes obesos / Evaluación de la discectomía lumbar endoscópica en pacientes obesos

ABSTRACT Objectives: Obesity is a public health problem with high morbidity and mortality rates and perioperative complications in the general population. Minimally invasive procedures are promising alternatives to perioperative complications in individuals with a high body mass index (BMI). Endoscopic lumbar discectomy has been gaining popularity in this regard. However, there are few descriptions in the literature about the endoscopic approach to improve pain and quality of life in obese individuals. Likewise, it is not determined whether individuals with a high BMI have more complications in this type of surgical approach. Methods: A longitudinal retrospective case-control study was performed with 63 subjects submitted to endoscopic discectomy, divided into 2 groups according to BMI (Group A, BMI ≥ 30kg/m2 and Group B, BMI <30kg/m2), in order to compare improvement in quality of life through the Oswestry Disability Index (ODI) and pain improvement by the Visual Analogue Scale (VAS), as well as to observe the incidence of postoperative complications in both groups. Results: There was no difference in postoperative ODI (p=0.36) and VAS (p=0.54) between groups, nor was there a statistical difference in the incidence of complications between groups (p=0.56). Conclusions: Endoscopic discectomy brings similar results in pain and quality of life in obese and non-obese patients without causing higher rates of complications. Level of Evidence III; Case-Control Study.

RESUMO Objetivos: A obesidade é um problema de saúde pública com taxas elevadas de morbimortalidade e complicações perioperatórias em relação à população em geral. Procedimentos minimamente invasivos são alternativas promissoras em relação às complicações perioperatórios nos indivíduos com Índice de Massa Corporal (IMC) elevado. A discectomia lombar endoscópica vem ganhando popularidade neste sentido. Todavia, há poucas descrições na literatura acerca da abordagem endoscópica na melhora da dor e qualidade de vida em indivíduos obesos. Da mesma forma, não está estabelecido se os indivíduos com IMC elevado apresentam mais complicações neste tipo de abordagem cirúrgica. Métodos: Estudo longitudinal retrospectivo tipo caso-controle com 63 indivíduos submetidos à discectomia endoscópica subdivididos em dois grupos de acordo com o IMC (Grupo A, IMC≥30Kg/m2 e Grupo B<30Kg/m2), afim de comparar a melhora na qualidade de vida pelo escore Oswestry Disability Index (ODI) e a melhora da dor pela Escala Visual Analógica (EVA), assim como observar a incidência de complicações pós-operatórias em ambos os grupos. Resultados: Não houve diferença nos escores ODI (p=0.36) e EVA (p=0.54) pós-operatórios entre os grupos, assim como não houve diferença estatística na incidência de complicações entre os grupos (p=0.56). Conclusões: A discectomia via endoscópica traz resultados semelhantes na dor e qualidade de vida em pacientes obesos e não obesos sem apresentar maiores taxas de complicações. Nível de Evidência III; Estudo de Caso-Controle.

RESUMEN Objetivos: La obesidad es un problema de salud pública con tasas elevadas de morbimortalidad y complicaciones perioperatorias en la población en general. Los procedimientos mínimamente invasivos son alternativas prometedoras en relación a las complicaciones perioperatorias en los individuos con índice de masa corporal (IMC) elevado. La discectomía lumbar endoscópica viene ganando popularidad en este sentido. Sin embargo, hay pocas descripciones en la literatura acerca del acceso endoscópico en la mejora del dolor y calidad de vida en individuos obesos. Del mismo modo, no está establecido si los individuos con IMC elevado tienen más complicaciones en este tipo de abordaje quirúrgico. Métodos: Estudio longitudinal retrospectivo tipo caso-control con 63 individuos sometidos a discectomía endoscópica, subdivididos en 2 grupos de acuerdo con el IMC (Grupo A, IMC ≥ 30 kg/m2 y Grupo B, IMC < 30 kg/m2), a fin de comparar la mejora en la calidad de vida por el score Oswestry Disability Index (ODI) y la mejora del dolor por la Escala Visual Analógica (EVA), así como observar la incidencia de complicaciones postoperatorias en ambos grupos. Resultados: No hubo diferencia en las puntuaciones ODI (p = 0,36) y EVA (p = 0,54) postoperatorios entre los grupos, así como no hubo diferencia estadística en la incidencia de complicaciones entre los grupos (p = 0,56). Conclusiones: La discectomía por vía endoscópica brinda resultados similares en el dolor y calidad de vida de pacientes obesos y no obesos sin causar tasas de complicaciones más altas. Nivel de Evidencia III; Estudio de Caso-Control.

Use of intraoperatory vancomycin in spinal surgeries / O uso da vancomicina intraoperatória em cirurgias de coluna / Uso de la vancomicina intraoperatoria en cirugías de columna

ABSTRACT Objectives: Despite the use of systemic antibiotic prophylaxis, infection is still a challenge for spine surgeons, with high morbidity and mortality, long hospitalization, delayed rehabilitation, and a greater number of interventions. The purpose of this cross-sectional retrospective case-control study was to compare the incidence of postoperative infection in individuals who received a systemic antibiotic as the sole prophylactic method with those who received vancomycin in the operative wound in association with systemic antibiotic prophylaxis in spinal surgery. Methods: We evaluated 2694 medical records of individuals submitted to posterior spinal surgery in the thoracolumbar segment in the period from January 2012 to June 2017, 1360 in the treatment group and 1334 in the control group. Results: Nineteen (1.39%) of the treatment group progressed with surgical site infection, compared to 42 (3.14%) of the control group. Conclusions: There was a significant reduction in the postoperative infection rate with the use of vancomycin (p=0.0379). Level of Evidence III; Case-Control Study.

RESUMO Objetivos: Apesar do uso de antibioticoprofilaxia sistêmica, a infecção ainda constitui um desafio para os cirurgiões de coluna, com alta morbimortalidade, longo período de internação, retardo na reabilitação e maior número de intervenções. O propósito deste estudo transversal retrospectivo tipo caso-controle foi comparar a incidência de infecção pós-operatória nos indivíduos que receberam antibiótico sistêmico como único método profilático aos que receberam Vancomicina na ferida operatória em associação com antibiótico sistêmico em cirurgias na coluna vertebral. Métodos: Foram avaliados 2694 prontuários de indivíduos submetidos à cirurgia de coluna por via posterior no segmento toracolombar no período de janeiro de 2012 a Junho de 2017, sendo 1360 no grupo tratamento e 1334 no grupo controle. Resultados: Dezenove (1,39%) do grupo tratamento evoluíram com infecção do sítio cirúrgico, em comparação com 42 (3.14%) do grupo controle. Conclusão: Houve redução significativa na taxa de infecção pós-operatória com o uso da Vancomicina (p=0,0379). Nível de Evidência III; Estudo de Caso-Controle.

RESUMEN Objetivos: A pesar del uso de profilaxis con antibióticos sistémicos, la infección todavía constituye un desafío para los cirujanos de columna, con alta morbimortalidad, largo período de internación, retraso en la rehabilitación y mayor número de intervenciones. El propósito de este estudio transversal retrospectivo tipo caso-control fue comparar la incidencia de infección postoperatoria en los individuos que recibieron antibiótico sistémico como único método profiláctico a los que recibieron vancomicina en la herida operatoria en asociación con antibiótico sistémico en cirugías de la columna vertebral. Métodos: Se evaluaron 2694 prontuarios de individuos sometidos a cirugía de columna por vía posterior en el segmento toracolumbar en el período de enero de 2012 a junio de 2017, siendo 1360 en el grupo tratamiento y 1334 en el grupo control. Resultados: Diecinueve (1,39%) del grupo de tratamiento evolucionó con infección del sitio quirúrgico, en comparación con 42 (3,14%) del grupo control. Conclusiones: Hubo reducción significativa en la tasa de infección postoperatoria con el uso de la vancomicina (p = 0,0379). Nivel de Evidencia III; Estudio de Caso-Control.

Thoracolumbar spondylodiscitis and the surgical approach: a retrospective analysis / Espondilodiscite toracolombar e a abordagem cirúrgica: uma análise retrospectiva / Espondilodiscitis toracolumbar y el enfoque quirúrgico: un análisis retrospectivo

ABSTRACT Objectives: Spondylodiscitis is a rare, late diagnosis disease. In view of the morbidity and mortality associated to the delayed diagnosis and increase of the cases in the last years, this study was carried out in order to evaluate the operated cases and improve the management of these patients.. Methods: Retrospective longitudinal study involving 1440 patients submitted to a surgical procedure in the thoracolumbar spine from January 2015 to March 2017, including 49 cases operated by spondylodiscitis. Results: Results: Severe complications requiring ICU admission (pulmonary or urinary tract sepsis and DVT) were observed in 7 (8.5%) individuals, whose mean hospital stay was 35 days (10-170 days) [p=0.006]. Conclusions: Conclusion: A correlation between the number of days hospitalized and the increase in the rate of complications was found. Early surgery by the anterior approach and posterior fixation after 2 weeks is the treatment of choice, with low morbidity and short period of hospitalization. Level of Evidence III; Retrospective Study.

RESUMO Objetivos: A espondilodiscite é uma rara doença, de diagnóstico tardio. Em vista da morbimortalidade associada ao atraso diagnóstico e aumento dos casos nos últimos anos, realizou-se este estudo a fim de avaliar os casos operados e aprimorar o manejo destes pacientes. Métodos: Estudo longitudinal retrospectivo, envolvendo 1440 pacientes submetidos a procedimento cirúrgico na coluna toracolombar de Janeiro de 2015 a Março de 2017, com inclusão de 49 casos operados por espondilodiscite. Resultados: As complicações graves com necessidade de UTI (sepse com foco pulmonar ou de vias urinárias e TVP) foram observadas em 7 (8.5%) indivíduos, cuja permanência hospitalar média foi de 35 dias (10-170 dias). [p=0.006]. Conclusão: Houve correlação entre a quantidade de dias internados e o aumento na taxa de complicações. A cirurgia precoce pela abordagem anterior e fixação posterior após duas semanas é o tratamento de escolha, com baixa morbidade e curto período de internamento. Nível de Evidência III; Estudo Retrospectivo.

RESUMEN Objetivos: La espondilodiscitis es una rara enfermedad, de diagnóstico tardío. En vista de la morbimortalidad asociada al retraso diagnóstico y el aumento de los casos en los últimos años, se realizó este estudio a fin de evaluar los casos operados y mejorar el manejo de estos pacientes. Métodos: Estudio longitudinal retrospectivo, involucrando a 1440 pacientes sometidos a procedimiento quirúrgico en la columna toracolumbar de enero de 2015 a marzo de 2017, con la inclusión de 49 casos operados por espondilodiscitis. Resultados: Las complicaciones graves con necesidad de UTI (sepsia con foco pulmonar o de vías urinarias y TVP) fueron observadas en 7 (8,5%) individuos, cuya permanencia hospitalaria media fue de 35 días (10-170 días) (p = 0,006). Conclusiones: Hubo correlación entre la cantidad de días internados y el aumento en la tasa de complicaciones. La cirugía precoz por el abordaje anterior y fijación posterior después de 2 semanas es el tratamiento de elección, con baja morbilidad y corto período de internamiento. Nivel de Evidencia III; Estudio Retrospectivo.

Redox status on different regions of the central nervous system of obese and lean rats treated with green tea extract.

OBJECTIVES: The purpose of this study was to evaluate some indicators of redox status, and inflammation on different regions of the central nervous system (CNS) of obese rats treated with green tea (GT). We hypothesized that obesity could affect the redox balance in different brain regions due to the diverse nature of the cells as well as the selective neuronal vulnerability to oxidative stress, and GT could triggers benefits effects restoring the redox status. METHODS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight) and obesity was induced by cafeteria diet (8 weeks). After this period, the animals were killed and brain tissue (cerebral cortex, cerebellum, and brainstem) was removed to evaluate oxidative stress and inflammation (cytokine release). RESULTS: We showed that the cafeteria diet had little effect on redox balance in the cerebral cortex and cerebellum; however, the brainstem was the region of the CNS most sensitive to cafeteria diet-induced redox unbalance. GFAP expression was increased in the cerebral cortex of obese rats and reduced by GT. It was also evident that GT treatment had numerous beneficial effects against oxidative damage to biomolecules in all brain regions analyzed. DISCUSSION: Our study established that different CNS regions show selective neuronal vulnerability when exposed to a diet enriched with fats and sugars, and the beneficial effect of GT was similar among these regions. We conclude that GT could be a good strategy for improving and maintaining brain function under healthy and pathological conditions.