Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Pharmacological effect of walnuts consumption on metabolic syndrome: a current view

Cardiovascular disease (CVD) is the leading cause of death worldwide (WHO, 2017). In addition to the global and national morbidity and mortality burdens of the disease, it imposes a substantial economic burden on society. The American heart association predicts that by 2035, 45% of Americans will suffer from CVD with costs expected to reach $1.1 trillion annually. Clinical trials have demonstrated that a nut-containing diet low in saturated fat and cholesterol, while high in poly and monounsaturated fatty acids has a beneficial effect on plasma lipids and lipoproteins when compared with either a low fat or average American diet. Other bioactive compounds present in walnuts, including micronutrients, fiber, and phytochemicals, may also contribute to their cardio protective effect by reducing inflammation, improving vascular reactivity, and lowering oxidative stress. It has been demonstrated that the consumption of walnuts resulted in significant reduction in body mass index (BMI), percentage of body fat, increased lean body mass and an increased amount of water in the body. A large population cohort study also demonstrated a marked reduction in body weight and other anthropometric parameters in people on regular consumption of walnuts.

Oxidative stress and its correlation with glycated haemoglobin in patients of type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) has a heavy disease burden and is one of the leading causes of death worldwide. Oxidative stress leads to the generation of inflammatory mediators and reactive oxygen species, which results in an inflammatory state, which plays a key role in the pathogenesis of diabetes and its complications. We aimed to correlate the levels of Glycated Haemoglobin with Oxidative Stress. Methods: This study included 200 subjects, 100 were type 2 diabetics and 100 healthy non-diabetic individuals. All the individuals were subjected to analysis of Fasting Plasma Glucose, Glycosylated Haemoglobin, Malondialdehyde, Superoxide Dismutase, Glutathione, Catalase, Uric Acid and Ascorbic Acid. The data thus generated was analyzed Statistically using the student 憈� test. ANOVA for comparison of mean in more than two groups. Pearson抯 coefficient of correlation was used to calculate the correlation between different parameters. p <0.05 was considered statistically significant. Results: The results showed that as the Glycated Hb increased, the levels of FBS, MDA, Uric acid increased and Serum SOD, Glutathione, Catalase, and Ascorbic acid levels decreased this change was statistically significant (p<0.05). A positive significant correlation between HbA1c, and fasting blood Glucose, MDA, Uric Acid. SOD, Catalase, Ascorbic Acid and Glutathione showed a negative correlation with glycosylated Haemoglobin. Conclusions: It is hereby concluded that when glycated Hb increases the natural antioxidants that are SOD, catalase, and glutathione decrease to combat the increased formation of ROS. Serum MDA, increased with increased glycated Hb and shows a positive correlation, indicating increasing lipid peroxidation.

Antioxidantes naturales y su efecto contra el estrés oxidante provocado por la contaminación por material particulado / Natural Antioxidants and their Effect Against Oxidative Stress Caused by Particulate Matter Pollution

Resumen La contaminación ambiental es uno de los factores que favorece el estrés oxidante, ya que expone al organismo a materiales diversos que generan radicales libres y afectan al sistema respiratorio, cardiovascular, inmunológico y nervioso de las personas más vulnerables como los niños, adultos mayores y personas con enfermedades crónicas. Para prevenir o reducir el estrés oxidante, el cual es un desequilibrio entre la producción de radicales libres y la capacidad del organismo de neutralizarlo, se recomienda consumir una dieta equilibrada y rica en antioxidantes naturales los cuales se encuentran diversos alimentos, especialmente en frutas y verduras con colores intensos, en las semillas y las especias. En las últimas décadas se ha demostrado la eficacia del consumo de antioxidantes naturales como: el resveratrol vino, el café, la curcumina, el ajo, la vitamina C, la vitamina E y el té verde que presentan efectos benéficos como: proteger membranas celulares, regular la expresión de genes relacionados con la inflamación, prevenir o reducir el daño endotelial, disminuir la frecuencia o severidad de enfermedades neurodegenerativas, hepáticas y pulmonares, así como estimular al sistema inmunológico.

Abstract Environmental pollution can promote oxidative stress by exposing the body to various elements and substances that generate free radicals, such as lead and vanadium. These free radicals can negatively impact the respiratory, cardiovascular, immune, and neurological systems of vulnerable populations, including children, the elderly, and those with chronic diseases. To prevent or reduce oxidative stress, it is recommended to consume a balanced diet rich in natural antioxidants. These antioxidants can be found in various foods, especially in fruits and vegetables with intense colors, seeds, and spices. In recent decades, the effectiveness of consuming natural antioxidants such as resveratrol found in wine, coffee, curcumin, garlic, vitamin C, vitamin E, and green tea has been demonstrated. These antioxidants have beneficial effects on the body, including the protection of cell membranes, regulation of gene expression associated with inflammation, prevention or reduction of endothelial damage, and the decrease or diminished severity of neurodegeneration, liver, and pulmonary disorders. Additionally, they stimulate the immune response.

Diferencia en las distintas funciones de las lipoproteínas de alta densidad en respuesta a la infección por SARS-CoV-2 / Differential Functions of High-density Lipoproteins in Response to SARS-CoV-2 Infection

RESUMEN Introducción. El síndrome post COVID (SPC), que se caracteriza por síntomas que se extienden superando las 4 semanas post-infección, podría desencadenar aumento en el riesgo cardiovascular. Las lipoproteínas de alta densidad (HDL) presentan funciones antiaterogénicas, como su capacidad para promover el transporte inverso del colesterol (TIC) y su actividad antioxidante, en la que es clave la enzima paraoxonasa 1 (PON 1). Objetivo. Evaluar funcionalidad de HDL en pacientes con SPC comparados con pacientes asintomáticos (PA) y controles. Material y métodos. Se incluyeron 9 individuos con SPC, 18 PA y 10 controles. Se midieron el hemograma, el perfil lipoproteico básico, las apolipoproteínas A-I y B, y marcadores inflamatorios por métodos automatizados. La actividad de PON 1 se evaluó empleando un método espectrofotométrico y los 3 pasos del TIC, eflujo de colesterol (ECC), y actividades de lecitina:colesterol aciltransferasa (LCAT) y proteína transportadora de colesterol esterificado (CETP), por métodos radiométricos. Resultados. No se observaron diferencias en sexo, edad, ni parámetros generales. El grupo PA presentó mayor actividad PON que los controles (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, en controles, PA y SPC, respectivamente; p=0,049). No se observaron diferencias en el TIC. El ECC (r=-0,45; p=0,049) y CETP (r=-0,38; p=0,028) correlacionaron negativamente con el índice neutrófilos/linfocitos. LCAT correlacionó inversamente con la ferritina (r=-0,34; p=0,046). Conclusiones. El incremento de PON 1 en el grupo PA representaría un mecanismo de defensa frente al estrés oxidativo post-infección. Todos los pasos del TIC mostraron una correlación negativa con marcadores inflamatorios. Nuestros resultados podrían explicar, en parte, el vínculo entre COVID y ateroesclerosis.

ABSTRACT Background. Post-COVID syndrome (PCS), characterized by symptoms that persist for more than 4 weeks after initial infection, could increase cardiovascular risk. High-density lipoproteins (HDL) have antiatherogenic functions, such as the ability to promote reverse cholesterol transport (RCT) and antioxidant activity. In this regard, paraoxonase 1 (PON 1) plays a key role. Objective. The aim of this study was to evaluate HDL functions in patients with PCS and compare them with asymptomatic patients (AP) and controls. Methods. The study included 9 patients with PCS, 18 AP and 10 controls. Complete blood count, basic lipoprotein profile, apolipoproteins A-I and B, and inflammatory markers were measured using automated methods. PON 1 activity was evaluated by a spectrophotometric assay, and the 3 steps of RCT, cellular cholesterol (efflux CCE), lecithin-cholesterol acyltransferase (LCAT) activity and cholesteryl ester transfer protein (CETP) activity were evaluated by radiometric assays. Results. There were no differences in sex, age, or general parameters. The AP group had higher PON activity than the control group (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, in controls, AP and PCS, respectively; p=0.049). There were no differences in RCT. Cellular cholesterol efflux (r=-0.45; p=0.049) and CETP (r=- 0.38; p=0.028) had a negative correlation with neutrophil-to-lymphocyte ratio. LCAT had an inverse correlation with ferritin (r=-0.34; p=0.046). Conclusions . Increased antioxidant activity of PON 1 would represent a defensive mechanism against oxidative stress after infection. All the RCT steps had a negative correlation with inflammatory markers. Our findings may explain, at least in part, the link between COVID-19 and atherosclerosis.

Morphological and Morphometric Analysis, Apoptosis and Oxidative Stress Study in Hep 2 Cells Treated by Resveratrol or Quercetine / Análisis Morfológico y Morfométrico, Estudio de Apoptosis y Estrés Oxidativo en Células Hep 2 Tratadas con Resveratrol o Quercetina

SUMMARY: Resveratrol (RES) and quercetine (QRC), is a promising agent relevant for both cancer chemoprevention and treatment via several signaling pathways, involved in their anticancer activity related to its chemotherapeutic potential, associated with the induction of ROS generation in cancer cells, leading to apoptosis. In our study, we have summarized the mechanisms of action of RES and QRC, and their pharmacological implications and potential therapeutic applications in cancer therapy. After treatment of Hep 2 cells with QRC or RES, the death pathways such as the cytochrome c release, ERK1/2 and IRS-1 pathways were upregulated, while cell survival pathway, including PI3K/AKT were downregulated. The RES and QRC caused oncosis, cells hypertrophy, hypercondensatin of chromatin, rupture of the plasma membrane and nuclear membrane, and formation of apoptotic bodies. Morphometric measurements of some cellular and nuclear parameters showed that RES and QRC induced an increase in cells and nuclear size, the nucleocytoplasmic ratio remained below 1 (N-Cyt R < 1), sign of low nuclear activity. The RES and QRC induced apoptosis of Hep2 cells by increasing of oxidative stress markers, MDA, and by modulating detoxifying enzymes, CAT and SOD. Our study results prove antiproliferative and proapoptotic properties of quercetin and resveratrol with regard to larynx cancer.

Resveratrol (RES) y quercetina (QRC), es un agente prometedor y relevante tanto para la quimioprevención como para el tratamiento del cáncer a través de varias vías de señalización, involucrado en su actividad anticancerígena relacionada con su potencial quimioterapéutico, asociado con la inducción de la generación de especies reactivas del oxígeno (ROS) en células cancerosas, lo que lleva a apoptosis. En nuestro estudio, hemos resumido los mecanismos de acción de RES y QRC, y sus implicaciones farmacológicas y posibles aplicaciones terapéuticas en la terapia del cáncer. Después del tratamiento de las células Hep 2 con QRC o RES, las vías de muerte, tal como la liberación de citocromo c, las vías ERK1/2 e IRS-1, se regulaban positivamente, mientras que la vía de supervivencia celular, incluida PI3K/AKT, se regulaba negativamente. El RES y el QRC provocaron oncosis, hipertrofia celular, hipercondensación de la cromatina, rotura de la membrana plasmática y nuclear y formación de cuerpos apoptóticos. Las mediciones morfométricas de algunos parámetros celulares y nucleares mostraron que RES y QRC indujeron un aumento en las células y el tamaño nuclear, la proporción nucleocitoplasmática se mantuvo por debajo de 1 (N- Cyt R <1), signo de baja actividad nuclear. RES y QRC indujeron la apoptosis de las células Hep2 aumentando los marcadores de estrés oxidativo, MDA, y modulando las enzimas desintoxicantes, CAT y SOD. Los resultados de nuestro estudio demuestran las propiedades antiproliferativas y proapoptóticas de la quercetina y el resveratrol con respecto al cáncer de laringe.

Relevance of copper/zinc ratio and its association with redox status in chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease is a progressive and persistent inflammatory condition associated with significant morbidity and mortality. Increased oxidative stress amongst others, plays an important role in the pathogenesis of this disease. The objective of the present study was to conduct a preliminary yet comprehensive examination of metal exposure specifically copper and zinc levels and their association with overall oxidative stress in COPD. Methods: A cross sectional study was carried out in a tertiary care hospital in South India. Two groups were included in the study. One group with 20 COPD patients and the other group of 20 healthy controls. Plasma samples were obtained from both the groups and serum levels of copper and zinc were studied by atomic absorption spectrometry. Cu/Zn ratio obtained from the results was further correlated with oxidative stress index calculated from total oxidant status and total antioxidant status in COPD with respect to controls. Results: The copper levels were significantly higher and the zinc levels lower in the COPD group as compared to the control group. The copper/zinc ratio was higher in COPD as compared to control population. The correlation between Cu/Zn ratio and oxidative stress index showed a positive correlation with a regression coefficient of 0.7. Conclusions: The study throws light on the trace element imbalance in COPD and how these could induce oxidative stress, contributing to persistent inflammation in COPD. In the clinical perspective, monitoring Cu/Zn ratio in COPD patients may lead to better risk mitigation and thereby better therapeutic management of the disease.

Amelioration of Diabetes Associated Hypo-testicular Co-morbidities in Rat by Aloe vera (L.): Potent Extract Selection Study

The experiment was framed to get the most effective extract of Aloe vera (L.) leaf gel for the amelioration of hypo-functional activity of testis in diabetic model rats. Only one frequency of streptozotocin was injected through skeletal muscle at 40 mg/kg body weight for diabetes induction. Treatment with aqueous or ethanol or methanol or hydro-ethanol (40:60) or hydro-methanol (40:60) extract of Aloe vera (L.) was continued for 28 days. Rats were euthanized and sacrificed on 29th day. Fasting blood glucose level, kinetics of hexokinase, androgenic key enzymes, and markers of cellular oxidative stress were assessed. The concentration of the sperm per milliliter of epididymal washed fluid, sperm motility, serum testosterone, plasma insulin levels, lipid, and metabolic toxicity sensors were also measured. Significant amelioration (p ? 0.05) of the negatively deviated above-mentioned parameters and the disrupted histomorphology of testicles towards vehicle-treated control were noted after uninterrupted 28 days of treatment to diabetic rats with the mentioned extracts of Aloe vera (L.). The highest percentage of recovery in the adopted sensors was noted in the hydro-ethanol extract-treated diabetes group than others. Hydro-ethanol extract of the said plant part is potent among all other extracts for correcting such hypo-function of testicles in diabetes.

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.

An Assessment of Ankle Function, Oxidative Damage, and Inflammatory Factor Levels in Minimally Invasive Ankle Joint Fusion Surgery for the Treatment of Traumatic Ankle Osteoarthritis

SUMMARY: Traumatic ankle osteoarthritis is a degenerative condition resulting from traumatic injuries. The objective of this study was to evaluate the impact of minimally invasive ankle joint fusion surgery on ankle function, oxidative damage, and inflammatory factor levels in traumatic ankle osteoarthritis patients. A total of 112 traumatic ankle osteoarthritis patients treated in our hospital from January 2022 to January 2023 were enrolled. They were randomly rolled into a control group (Group C) and an experimental group (Group E), with the former undergoing conventional open ankle joint fusion surgery and the latter receiving minimally invasive ankle joint fusion surgery. A comparison was made between the two groups based on American Orthopedic Foot and Ankle Society (AOFAS), bony fusion rates, and visual analog scale (VAS) scores at pre-operation, and at 1, 2, and 3 months post-operation. Additionally, serum oxidative damage indicators and inflammatory factor levels were measured to evaluate the recovery effects in both groups. Relative to Group C, Group E showed drastically increased AOFAS scores and bony fusion rates (P<0.05), as well as greatly decreased VAS scores (P<0.05). Moreover, Group E exhibited more pronounced improvements in oxidative damage indicators and inflammatory factors versus Group C (P<0.05). Minimally invasive ankle joint fusion surgery drastically improves ankle function in traumatic ankle osteoarthritis patients and reduces levels of oxidative damage and inflammatory response. This provides an important clinical treatment option.

La osteoartritis traumática del tobillo es una afección degenerativa resultante de lesiones traumáticas. El objetivo de este estudio fue evaluar el impacto de la cirugía mínimamente invasiva de fusión de la articulación talocrural sobre la función del tobillo, el daño oxidativo y los niveles de factor inflamatorio en pacientes con osteoartritis traumática del tobillo. Se inscribieron un total de 112 pacientes con artrosis traumática de tobillo tratados en nuestro hospital desde enero de 2022 hasta enero de 2023. Fueron divididos aleatoriamente en un grupo de control (Grupo C) y un grupo experimental (Grupo E), donde el primero se sometió a una cirugía de fusión de la articulación talocrural abierta convencional y el segundo recibió una cirugía de fusión de la articulación talocrural mínimamente invasiva. Se realizó una comparación entre los dos grupos según la Sociedad Estadounidense de Ortopedia de Pie y Tobillo (AOFAS), las tasas de fusión ósea y las puntuaciones de la escala visual analógica (EVA) antes de la operación y 1, 2 y 3 meses después de la operación. Además, se midieron los indicadores de daño oxidativo sérico y los niveles de factor inflamatorio para evaluar los efectos de la recuperación en ambos grupos. En relación con el grupo C, el grupo E mostró puntuaciones AOFAS y tasas de fusión ósea drásticamente aumentadas (P <0,05), así como puntuaciones VAS muy disminuidas (P <0,05). Además, el grupo E exhibió mejoras más pronunciadas en los indicadores de daño oxidativo y factores inflamatorios en comparación con el grupo C (P <0,05). La cirugía de fusión de la articulación talocrural mínimamente invasiva mejora drásticamente la función del tobillo en pacientes con osteoartritis traumática del tobillo y reduce los niveles de daño oxidativo y la respuesta inflamatoria. Esto proporciona una importante opción de tratamiento clínico.

Evaluation of the Effects of Alpha-Tocopherol, Quercetin and their Combination on Ethanol-Induced Pancreatic and Duodenal Mucosal injuries: An Experimental Study

Aim: In this study, the effects of alpha-tocopherol (AT), quercetin (QT) or their combination on ethanol-induced pancreatic and duodenal mucosal damage were investigated in rats using morphological and biochemical evaluations.Study Design: Experimental study.Place and Duration of Study: University of Ibadan, Ibadan, Nigeria.Methodology: Ethanol-induced injuries were produced by oral administration of 40% ethanol (0.2 ml/day) for 40 consecutive days, while a control group of rats was served distilled water. Other groups received AT (2.5 mg/kg), QT (50 mg/kg) or their combination with 40% ethanol during the experimental period.Results: Blood glucose level was significantly (p<0.05) increased in ethanol-treated rats relative to controls. Ethanol administration caused shrinkage of insulin-secreting islets tissues in the pancreas, while lesions such as erosions, loss of villi and severe inflammatory cell infiltrations of the mucosa and sub-mucosa were observed in the duodenum. These changes were accompanied by significant elevation in the levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) in the pancreas and duodenum, along with reduced activities of glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with AT, QT, and especially their combination, yielded profound reversal of ethanol-induced effects indicated by restoration of blood glucose to control levels, preservation of pancreatic and duodenal morphology and the inhibition of ethanol-induced oxidative stress.Conclusion: Overall, dietary supplementation with AT and/or QT could potentially counteract the adverse effects associated with chronic alcohol consumption.

El estrés oxidativo en el perioperatorio: implicaciones clínicas / Oxidative stress in the perioperative period: clinical implications

Resumen: El trauma de la cirugía altera la homeostasis y desarrolla complicaciones en el postoperatorio, particularmente en los pacientes de alto riesgo. Las respuestas al estrés quirúrgico se producen por un proceso inflamatorio agudo y por un estado de desbalance entre los niveles de moléculas prooxidantes y la actividad de los sistemas antioxidantes conocido como estrés oxidativo (EOx). Estos dos mecanismos subyacen a las complicaciones en el perioperatorio. Por otro lado, las complicaciones pueden disminuirse con el manejo anestésico adecuado, ya que algunos anestésicos presentan capacidad antioxidante. El EOx puede tener un impacto negativo en todas las formas de cirugía mayor, particularmente en los pacientes de edad avanzada y con comorbilidades, por lo que es importante disminuir o evitar este fenómeno. El objetivo de esta revisión es presentar brevemente el concepto y las bases celulares del EOx y su relación con las complicaciones más comunes en el perioperatorio de cirugía cardíaca y no cardíaca, así como la determinación cuantitativa del nivel de EOx mediante biomarcadores séricos. Además, se revisa el efecto de los anestésicos sobre el EOx y el uso de terapias antioxidantes en la prevención de las complicaciones postoperatorias inducidas por el EOx.

Abstract: The trauma of surgery induces systemic stress that alters homeostasis and develops postoperative complications, particularly in high-risk patients. Surgical stress is produced by an acute inflammatory process and by the imbalance between the levels of pro-oxidant molecules and the activity of antioxidant systems. This imbalance is known as oxidative stress (OS). These two mechanisms underlie perioperative complications are reduced with anaesthetic management since some anaesthetics have antioxidant capacity. OS could negatively impact all forms of major surgery, particularly in elderly patients and patients with comorbidities. This review aims to present the concept and cellular bases of OS and its relationship with the most common complications in the perioperative period of cardiac and non-cardiac surgery, as well as the quantitative determination of the level of OS through serum biomarkers. Furthermore, the effect of anaesthetics on OS and the use of antioxidant therapies in preventing postoperative complications induced by OS are reviewed.

Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model / Efeito do octreotide no estresse oxidativo em eritrócitos e no tecido renal no modelo de síndrome nefrótica experimental induzida por adriamicina

Abstract Introduction: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. Methods: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. Results: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. Conclusions: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Resumo Introdução: Síndrome nefrótica (SN) é uma das causas de doença renal em estágio terminal. É importante elucidar a patogênese e oferecer novas opções de tratamento. Estresse oxidativo pode desencadear a patogênese sistemicamente ou isoladamente nos rins. O octreotide (OCT) tem efeitos antioxidantes benéficos. Nosso objetivo foi investigar a fonte de estresse oxidativo e efeito do OCT no modelo experimental de SN. Métodos: Dividimos 24 ratos albinos Wistar não urêmicos em 3 grupos. Grupo controle, 2 mL de solução salina intramuscular (im); grupo SN, adriamicina 5 mg/kg intravenosa (iv); grupo tratamento SN, adriamicina 5 mg/kg (iv) e OCT 200 mcg/kg (im) foram administrados no início do estudo (Dia 0). Aos 21 dias, mediram-se os níveis de creatinina e proteína em amostras de urina de 24 horas. Mediu-se a catalase (CAT) eritrocitária e renal e a substância reativa ao ácido tiobarbitúrico (TBARS). Avaliou-se também histologia renal. Resultados: Não houve diferença significativa entre os três grupos em termos de CAT e TBARS em eritrócitos. O nível de CAT renal foi menor no grupo SN e significativamente menor que no grupo controle. No grupo tratamento, o nível de CAT aumentou significativamente em comparação com o grupo SN. Quanto à histologia renal, as avaliações tubular e intersticial foram semelhantes em todos os grupos. O escore glomerular foi significativamente maior no grupo SN em comparação com o grupo controle e diminuiu significativamente no grupo de tratamento em comparação com o grupo SN. Conclusões: Estresse oxidativo na SN pode ser devido à diminuição do mecanismo de proteção antioxidante nos rins. O octreotide melhora níveis de antioxidantes e histologia do tecido renal e pode ser uma opção de tratamento.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

Influencia del consumo de hidratos de carbono sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional / Influence of carbohydrate intake on oxidative status among women with and without gestational diabetes mellitus

RESUMEN Objetivo: Identificar la influencia del consumo de hidratos de carbono (HCO) sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional (DMG). Materiales y métodos: Se realizó un estudio transversal, observacional y comparativo a dos grupos de 21 mujeres con y sin DMG, respectivamente, en la ciudad de Toluca, México, de enero a diciembre del 2022. Para evaluar parámetros sociodemográficos, se les aplicó un cuestionario de historia clínica; en cuanto a los parámetros antropométricos, se les midió peso corporal y estatura; y respecto a los parámetros bioquímicos, colesterol total (CT) y triglicéridos (TG). Para evaluar el estado oxidante/antioxidante se cuantificaron, como marcador oxidante, el malondihaldeído (MDA), y como antioxidantes, catalasa (cat), superóxido dismutasa (SOD) y capacidad antioxidante total (CAT). Los hábitos dietéticos se evaluaron a través de un recordatorio de 24 horas, en ambos grupos de mujeres, para obtener los macronutrientes: proteínas, lípidos e HCO. A partir de los hidratos de carbono totales (HCOT), se calcularon los hidratos de carbono complejos (HCOC) e hidratos de carbono simples (HCOS) como la sacarosa. Para el cálculo de HCOS por día, se usó la lista de alimentos con contenido de sacarosa por cada 100 gramos de consumo que emplea el Sistema Mexicano de Equivalentes; para el análisis de dieta, se utilizó el programa Nutrikcal VO. Se usaron las pruebas estadísticas t de Student para muestras independientes, U de Mann-Whitney para las variables no homogéneas y se realizó la correlación de Spearman (p < 0,05) en el programa SPSS, versión 19. Resultados: Los resultados mostraron que la diferencia entre los valores de CT (p < 0,029), TG (p < 0,029), las enzimas: cat (p < 0,011), SOD (p < 0,013), así como el MDA (p < 0,039), fueron significativamente mayores en las pacientes del grupo con DMG en comparación con el grupo sin DMG. Además, el grupo con DMG consumió mayor proporción de sacarosa. Conclusiones: Las mujeres con DMG tienen un desequilibrio en el estado oxidante/antioxidante influenciado por el tipo de HCO que consumen, en particular los HCOS como la sacarosa.

ABSTRACT Objective: To identify the influence of carbohydrate (CHO) intake on oxidative status among women with and without gestational diabetes mellitus (GDM). Materials and methods: A cross-sectional, observational and comparative study was carried out with two groups of 21 women each with and without GDM in the city of Toluca, Mexico, from January to December 2022. The sociodemographic parameters were determined by administering the patients a medical history questionnaire; anthropometric parameters such as body weight and height were measured; and biochemical parameters including total cholesterol (TC) and triglycerides (TG) were calculated. The oxidant/antioxidant status was assessed as follows: malondialdehyde (MDA) as oxidative stress marker; and catalase (CAT), superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidants. Dietary habits were evaluated through a 24-hour reminder in both groups of women to obtain the macronutrient classes, i.e., proteins, fats and CHOs. Based on the total carbohydrates (TCHOs), complex (CCHOs) and simple carbohydrates (SCHOs) such as sucrose were calculated. SCHOs per day were measured using the list of foods with sucrose content per 100 grams according to the Mexican Food Equivalence System (SMAE). The NutriKcal VO program was used for the dietary analysis. Statistical tests such as Student's t test and Mann-Whitney U test were performed for the independent samples and nonhomogeneous variables, respectively, and Spearman's rank correlation coefficient (p < 0.05) was determined using the IBM SPSS Statistics V19. Results: The results showed that the difference between the levels of TC (p < 0.029), TG (p < 0.029), enzymes CAT (p < 0.011) and SOD (p < 0.013), as well as MDA (p < 0.039) was significantly higher among patients in the group with GDM compared to that in the group without GDM. In addition, the group with GDM consumed a higher proportion of sucrose. Conclusions: Women with GDM have an imbalance in the oxidant/antioxidant status, influenced by the type of CHO they consume, particularly SCHOs such as sucrose.

Earthworm Protein Protects Vascular Endothelial Function in Spontaneously Hypertensive Rats via PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10-3 g·kg-1·d-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg-1·d-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe2+）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Anti-aging Effect of Ginseng Radix et Rhizoma：A Review / 中国实验方剂学杂志

Ginseng Radix et Rhizoma（GRR） has the function of replenishing vital energy and can lighten the body and prolong the life when taken for a long time， which is suitable for the development of anti-aging products， so this paper intends to sort out the progress of anti-aging research on GRR. After combing， the results of modern studies have shown that a variety of components in GRR have anti-aging effect， which can prolong the lifespan of aging animal models， as well as delay the aging of various systems. The anti-aging mechanisms mainly include anti-cellular senescence， anti-oxidative stress， inhibiting telomere shortening， maintaining mitochondrial homeostasis and so on. The anti-aging ingredients of GRR involved in the researches mainly include ginsenoside Rg1 and ginsenoside Rb1， in addition， ginsenoside Rg3， ginsenoside Rd， ginsenoside Rg2， ginsenoside Re， ginsenoside Rb2， oligosaccharides of GRR， polysaccharides of GRR， water extract of GRR， total saponins of Panax ginseng stems and leaves are also included. Therefore， under current background of population aging， the in-depth development of GRR and its transformation into anti-aging products are of great significance for delaying senility and improving the health conditions of aging population.