Etoposide Model-Induced Changes in Antioxidant Studies Histological and Ultrastructural Evaluations of Hepatic, Renal, and Cardiac Tissues of Male Rats / Cambios Inducidos por el Modelo de Etopósido en Estudios de Antioxidantes, Evaluaciones Histológicas y Ultraestructurales de Tejidos Hepáticos, Renales y Cardíacos de Ratas Macho

SUMMARY: Etoposide is an effective antimitotic and antineoplastic agent used to treat various human malignancies. In the present study, Etoposide was injected intraperitoneally into the rats at 1 mg/kg/day for 52 days (52 doses). The control animals received physiological saline (0.5 ml) intraperitoneally daily for 52 doses. The body weight of etoposide-treated rats was significantly reduced compared to control rats. Lipid peroxidation demonstrated an insignificant rise in hepatic tissue, a non-significant decline in renal tissue, and a significant reduction in cardiac tissue. The levels of GSH in hepatic and renal tissue were found to be non-significantly increased but significantly increased in cardiac tissue compared to controls. GR activity was found to be considerably decreased in the treated group. G-S-T levels increased significantly in all treated group. Etoposide injections caused a non-significant change in the GPX level of hepatic tissue, whereas renal and cardiac tissues showed a significant increase. The activity of CAT in hepatic tissue was significantly increased, while CAT activity in renal tissue showed a non-significant decrease, whereas in cardiac tissue, significantly lower levels were observed than in control group. The level of CYTp450 in hepatic and cardiac tissues showed a significant increase; however, renal tissue showed non-significant depletion, whereas CYTb5 in hepatic, renal, and cardiac tissues was significantly lower than controls. The protein content in the hepatic tissue was not significantly increased, whereas the total protein in the renal and cardiac tissues was increased significantly. The research finding is indicative of detoxification activity in the etoposide model.

El etopósido es un agente antimitótico y antineoplásico eficaz que se utiliza para tratar diversas neoplasias malignas humanas. En el presente estudio, se inyectó etopósido por vía intraperitoneal a las ratas a razón de 1 mg/kg/día durante 52 días (52 dosis). Los animales control recibieron solución salina fisiológica (0,5 ml) por vía intraperitoneal diariamente por 52 dosis. El peso corporal de las ratas tratadas con etopósido se redujo significativamente en comparación con las ratas del grupo control. La peroxidación lipídica demostró un aumento insignificante del tejido hepático, una disminución no significativa del tejido renal y una reducción significativa del tejido cardíaco. Se encontró que los niveles de GSH en el tejido hepático y renal no aumentaron significativamente, pero sí aumentaron significativamente en el tejido cardíaco en comparación con los controles. Se encontró que la actividad de GR disminuyó considerablemente en el grupo tratado. Los niveles de G-S-T aumentaron significativamente en todos los grupos tratados. Las inyecciones de etopósido provocaron un cambio no significativo en el nivel de GPX del tejido hepático, mientras que los tejidos renal y cardíaco mostraron un aumento significativo. La actividad de CAT en el tejido hepático aumentó significativamente, mientras que la actividad de CAT en el tejido renal mostró una disminución no significativa, mientras que en el tejido cardíaco se observaron niveles significativamente más bajos que en el grupo de control. El nivel de CYTp450 en los tejidos hepático y cardíaco mostró un aumento significativo; sin embargo, el tejido renal mostró un agotamiento no significativo, mientras que CYTb5 en los tejidos hepático, renal y cardíaco fue significativamente menor que los controles. El contenido de proteínas en el tejido hepático no aumentó significativamente, mientras que la proteína total en los tejidos renal y cardíaco aumentó significativamente. El hallazgo de la investigación es indicativo de la actividad de desintoxicación en el modelo de etopósido.

Prospective Protective Effects of Arthrospira platensis Against Acetaminophen Induced Hepato-Renal Toxicity in Rats / Efectos Protectores Prospectivos de Arthrospira platnesis Contra la Toxicidad Hepatorrenal Inducida por Paracetamol en Ratas

SUMMARY: The toxic effects of acetaminophen appear primarily in the liver and kidney. The protective effect of blue green alga Arthrospira platensis on hepato-renal toxicity caused by acetaminophen was evaluated in male rats. The obtained results showed that subcutaneous injection of acetaminophen at a dose 120 &240 սl acetaminophen/kg by weight resulted in an observed elevation in the enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP), serum total lipids, total cholesterol, creatinine, total bilirubin, urea, nitric oxide (NO), L- malondialdehyde (MDA) and interleukins (IL-2 &IL-6). However, there is a decrease in the serum total protein, albumin and loss in antioxidant enzyme activities in liver including; superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH). This effect was found to be dose and time dependent. In spite of, pre- oral administration of Arthrospira platensis 1000 mg/kg .b. wt. prior acetaminophen injection succeeded to modulate the effect of the observed abnormalities caused by acetaminophen. Moreover, there were no remarkable changes in serum biomarkers of rats received Arthrospira platensis only at a dose of 1000 mg/kg by weight (group 2). The histopathological findings confirm the biochemical results that indicates the safety use of Arthrospira platensis at the selected dose in this study. Therefore, the present results clarified the protective effect of blue green alga Arthrospira platensis on oxidative stress, hepatic and nephrotoxicity induced by acetaminophen in male Wister rats.

Los efectos tóxicos del paracetamol aparecen principalmente en el hígado y el riñón. Se evaluó en ratas macho Wistar el efecto protector del alga verde azulada Arthrospira platensis sobre la toxicidad hepatorrenal causada por paracetamol. Los resultados obtenidos mostraron que la inyección subcutánea de paracetamol a dosis de 120 y 240 µl de paracetamol/kg, resultó en una elevación en las actividades enzimáticas de la aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (ALP), lípidos séricos totales, colesterol total, creatinina, bilirrubina total, urea, óxido nítrico (NO), L- malondialdehído (MDA) e interleucinas (IL-2 e IL-6). Sin embargo, hay una disminución en la proteína sérica total, albúmina y pérdida en las actividades de las enzimas antioxidantes en el hígado, incluyendo; superóxido dismutasa (SOD), catalasa (CAT) y glutatión reductasa (GSH). Se encontró que este efecto era dependiente de la dosis y el tiempo. A pesar de la administración preoral de Arthrospira platensis 1000 mg/kg, la inyección previa de acetaminofeno logró modular el efecto de las anormalidades observadas causadas por el acetaminofeno. Además, no hubo cambios notables en los biomarcadores séricos de ratas que recibieron Arthrospira platensis solo a una dosis de 1000 mg/kg (Grupo 2). Los hallazgos histopatológicos confirman los resultados bioquímicos que indican la seguridad del uso de Arthrospira platensis a la dosis seleccionada en este estudio. Por lo tanto, los presentes resultados aclararon el efecto protector del alga verde azulada Arthrospira platensis sobre el estrés oxidativo, la toxicidad hepática y la nefrotoxicidad inducida por paracetamol en ratas Wistar macho.

Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

Screening for acetylcholinesterase inhibition, lipid peroxidation inhibition and antioxidant activity of medicinal plants from Morocco / Detección de inhibición de acetilcolinesterasa, inhibición de peroxidación de lípidos y actividad antioxidante de plantas medicinales de Marruecos

Acetylcholinesterase (AChE), hydrolyzes acetylcholine to choline and acetate, thereby terminating this neurotransmitter effect at cholinergic synapses. Therefore, AChE inhibition is used for counterbalance the cholinergic deficit in Alzheimer's disease (AD) patients. In the present work, in order to find new plant acetylcholinesterase inhibitors, the hydroalcoholic extracts from seventeen medicinal plant species were screened for their acetylcholinesterase inhibition activity, as well as total phenolic (TPC) and flavonoids contents (TFC) and antioxidant activity using ORAC (Oxygen Radical Absorbance Capacity) assay, and their ability to inhibit lipid peroxidation. The results revealed that Rumex acetosa, Taraxacum officinale and Hypericum perforatum extracts possessing the highest TPC and TFC, were the most effective in terms of ORAC antioxidant activity, and acetylcholinesterase inhibition, in addition to their ability to inhibit liposomes peroxidation, suggesting that those plant species may provide a substantial source of secondary metabolites, which act as natural antioxidants and acetylcholinesterase inhibitors, and may be beneficial in the treatment of AD.

La acetilcolinesterasa (AChE) hidroliza la acetilcolina se hidroliza en colina y acetato, terminando así este efecto neurotransmisor en las sinapsis colinérgicas. Por lo tanto, la inhibición de la AChE se utiliza para contrarrestar el déficit colinérgico en pacientes con enfermedad de Alzheimer (EA). En el presente trabajo, con el fin de encontrar nuevos inhibidores de la acetilcolinesterasa vegetal, se analizaron los extractos hidroalcohólicos de diecisiete especies de plantas medicinales para determinar su actividad inhibidora de la acetilcolinesterasa, así como el contenido total de fenólicos (TPC) y flavonoides (TFC) y la actividad antioxidante utilizando ORAC (Capacidad de absorbancia de radicales de oxígeno) y su capacidad para inhibir la peroxidación de lípidos. Los resultados revelaron que los extractos de Rumexacetosa, Taraxacum officinale e Hypericum perforatum que poseen los más altos TPC y TFC, fueron los más efectivos en términos de actividad antioxidante ORAC e inhibición de acetilcolinesterasa, además de su capacidad para inhibir la peroxidación de los liposomas, sugiriendo que esas especies de plantas puede proporcionar una fuente sustancial de metabolitos secundarios, que actúan como antioxidantes naturales e inhibidores de la acetilcolinesterasa, y puede ser beneficioso en el tratamiento de la EA.

Ferroptosis and drug-induced liver injury / 中华肝脏病杂志

Ferroptosis is a type of regulated cell death driven by iron-dependent lipid peroxidation that has received extensive attention in recent years. A growing body of evidence suggests that ferroptosis contributes to the progression of drug-induced liver injury. Therefore, the role and mechanism of ferroptosis in the process of drug-induced liver injury deserve further extensive and in-depth exploration, which will aid in the discovery of novel biomarkers as well as the identification of potential approches of targeting ferroptosis to intervene in drug-induced liver injury.

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates / O efeito inibitório de Cannabis Sativa L. e Morus nigra L. contra a peroxidação lipídica em homogenatos de fígado e cérebro de cabra

Abstract The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Resumo O presente estudo teve como objetivo avaliar o potencial antioxidante e o efeito inibitório de Cannabis sativa e Morus nigra contra a peroxidação lipídica em homogenatos de cérebro e fígado de cabras. A formação de radicais livres, espécies altamente reativas de oxigênio (ROS) e espécies reativas de nitrogênio (RNS), é um processo metabólico normal para sinalização celular e combate aos antígenos. No entanto, eles podem causar sérios danos se forem produzidos em portagens ampliadas. Além disso, distúrbios metabólicos também servem como fontes dessas espécies reativas, embora o problema possa ser resolvido por meio de suplementos e outros fitoquímicos. Neste estudo, duas espécies de plantas foram avaliadas quanto ao seu potencial biológico, empregando um espectro de ensaios antioxidantes. A atividade antioxidante foi realizada por ensaio de peroxidação lipídica. O extrato de água preparado a partir de folhas de Cannabis sativa e Morus nigra mostrou inibição significativa (P < 0,05) em comparação com o controle, ou seja, 522,6 ± 0,06 e 659,97 ± 0,03 µg / mL contra peroxidação lipídica induzida por ferro em homogenato de cérebro de cabra, enquanto as inibições foram 273,54 ± 0,04 e 309,18 ± 0,05 µg / mL contra a peroxidação lipídica do cérebro induzida por nitroprussiato. A peroxidação lipídica induzida por ferro e nitroprussiato também foi significativamente inibida por extratos de folhas de Cannabis sativa e Morus nigra em homogenatos de fígado, como 230,63 ± 0,52 e 326,91 ± 0,01 µg / mL (induzida por ferro), enquanto 300,47 ± 0,07 e 300,47 ± 0,07 µg / mL (induzida por nitroprussiato), respectivamente. Os extratos do extrato de Cannabis sativa apresentaram atividade promissora (96,04 ± 0,060%) contra os radicais DPPH enquanto Morus nigra apresentou atividade moderada (34,11 ± 0,120%). Os resultados sugerem que diferentes acessos de Cannabis sativa e Morus nigra são uma fonte potencial de antioxidantes e têm efeito terapêutico contra doenças induzidas por estresse oxidativo e, portanto, podem ser usados ​​para a descoberta e desenvolvimento de novos medicamentos.

Grado de oxidación en pacientes con Diabetes Mellitus Tipo 2 / Oxidation degree in patients with Type 2 Diabetes Mellitus

La peroxidación lipídica es un proceso complejo que hace referencia a la degradación oxidativa de los lípidos, a través del cual los radicales libres capturan electrones de los lípidos en las membranas celulares, lo cual compromete la integridad y la función de la membrana. Mediante una serie de reacciones en cadena, se forman los peróxidos lipídicos que se degradan para formar compuestos reactivos como el malondialdehído (MDA) y 4-hidroxinonenal, los cuáles pueden ser cuantificados por diferentes metodologías. Objetivo: El presente trabajo se realizó con la finalidad establecer el grado de oxidación en una población con diabetes tipo 2 (DM2).Métodos: Estudio descriptivo, analítico y transversal; muestra de 55 personas, conformada por 30 controles entre 25-35 años y 25 pacientes con DM2 entre 25-50 años, se les determinó glicemia, triglicéridos, colesterol total, HDL-Colesterol y LDL-Colesterol por método colorimétrico enzimático, así como se determinó la concentración de 4-hidroxinonenal como un marcador de estrés oxidativo Resultados: Los valores de 4-hidroxinonenal en la población control oscilaron entre 2,61y 6,83 µmol/L y en los diabéticos de 28,99 y 73,74 µmol/L., encontrándose diferencias estadísticamente significativas entre ambas poblaciones, así como en el perfil lipídico y en la glicemia entre ambos grupos. Conclusión: Los resultados demuestran una elevación de la peroxidación lipídica en pacientes diabéticos, lo cual es indicativo de estrés oxidativo y riesgo adicional en estos pacientes que podrían conllevar a las complicaciones crónicas dela diabetes tipo 2(AU)

Lipid peroxidation is a complexprocess that refers to the oxidative degradation of lipids, through which free radicals capture electrons from lipids incell membranes, which compromises the integrity and functionof the membrane. Trough a series of chain reactions, lipidperoxides are formed that degrade to form reactive compoundssuch as malondialdehyde (MDA) and 4-hydroxynonenal, whichcan be quantified by different methodologies. Objective: The present work was carried out with the purpose ofestablishing the degree of oxidation in a population withtype 2 diabetes (DM2). Methods: the sample was 55 people,made up of 30 controls between 25-35 years and 25 patientswith DM2 and between 25-50 years, glycemia, triglycerides,total cholesterol, HDL-Cholesterol and LDL-Cholesterol were etermined by colorimetric method. enzymatic, as well as theconcentration of 4-hydroxynonenal was determined as a markerof oxidative stress. Results: The values of 4-hydroxynonenal inthe control population ranged between 2.61 and 6.83 µmol/Land in diabetics 28.99 and 73.74 µmol/L., finding statisticallysignificant differences between both populations, as well as inthe lipid profile and glycemia between both groups. Conclusion:The results show an elevation of lipid peroxidation in diabeticpatients, which is indicative of oxidative stress and additionalrisk in these patients that could lead to chronic complications oftype 2 diabetes(AU)

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

Pharmacological action of quercetin against testicular dysfunction: A mini review / 中西医结合学报

The testis is an immune-privileged organ susceptible to oxidative stress and inflammation, two major factors implicated in male infertility. A reduction in the concentration and activities of testicular function biomarkers has been shown to correlate with impaired hypothalamic-pituitary-testicular axis and oxidative stress. However, the use of natural products to ameliorate these oxidative stress-induced changes may be essential to improving male reproductive function. Quercetin possesses several pharmacological activities that may help to combat cellular reproduction-related assaults, such as altered sperm function and reproductive hormone dysfunction, and dysregulated testicular apoptosis, oxidative stress, and inflammation. Studies have shown that quercetin ameliorates testicular toxicity, largely by inhibiting the generation of reactive oxygen species, with the aid of the two antioxidant pharmacophores present in its ring structure. The radical-scavenging property of quercetin may alter signal transduction of oxidative stress-induced apoptosis, prevent inflammation, and increase sperm quality in relation to the hormonal concentration. In this review, the therapeutic potential of quercetin in mediating male reproductive health is discussed.

Estimation of salivary malondialdehyde Levels in smokeless tobacco chewers with chronic periodontitis-A cross sectional clinico biochemical study / Estimación de los niveles de malondialdehído salival en masticadores de tabaco sin humo con periodontitis crónica: un estudio bioquímico clínico transversal

ABSTRACT: Despite the reported effects of smokeless tobacco (ST) on the periodontium and high prevalence of ST use in rural populations and in males studies on this specific topic are limited. The purpose of this cross-sectional investigation was to measure lipid peroxidation (as an end product of oxidative stress) end product i.e. Malondialdehyde (MDA) in saliva of patients with gingivitis, chronic periodontitis and to assess the influence of smokeless tobacco on Salivary Malondialdehyde (S-MDA). Total 30 patients with gingivitis, 30 with chronic periodontitis and 30 Smokeless Tobacco Chewers with Chronic Periodontitis and 30 periodontally healthy subjects were included in the study. Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PD), and Clinical Attachment Loss (CAL) were recorded followed by stimulated Saliva sample collection. Salivary MDA Levels were assessed by UV Spectrophotometry. There was a statistically significant increase in the salivary MDA levels in gingivitis, chronic periodontitis and in smokeless tobacco chewers with chronic periodontitis when compared with healthy group. Higher salivary MDA levels in gingivitis group, chronic periodontitis, and smokeless tobacco chewers with chronic periodontitis reflects increasedoxygen radical activity during periodontal inflammation.

RESUMEN: A pesar de los efectos reportados del tabaco sin humo (TS) sobre el periodonto y la alta prevalencia del uso de TS en poblaciones rurales y en hombres, los estudios sobre este tema específico son limitados. El propósito de esta investigación transversal fue medir el producto final de la peroxidación lipídica (como producto final del estrés oxidativo), es decir, malondialdehído (MDA) en la saliva de pacientes con gingivitis, periodontitis crónica y evaluar la influencia del tabaco sin humo en el malondialdehído salival (S-MDA). Se incluyeron en el estudio un total de 30 pacientes con gingivitis, 30 con periodontitis crónica y 30 masticadores de tabaco sin humo con periodontitis crónica y 30 sujetos periodontalmente sanos. Se registraron el índice de placa (PI), el índice gingival (GI), la profundidad de la bolsa de sondeo (PD) y la pérdida de adherencia clínica (CAL), seguidos de la recogida de muestras de saliva estimuladas. Los niveles de MDA en saliva se evaluaron mediante espectrofotometría UV. Hubo un aumento estadísticamente significativo en los niveles de MDA en saliva en gingivitis, periodontitis crónica y en masticadores de tabaco sin humo con periodontitis crónica en comparación con el grupo sano. Los niveles más altos de MDA en saliva en el grupo de gingivitis, periodontitis crónica y masticadores de tabaco sin humo con periodontitis crónica reflejan un aumento de la actividad de los radicales de oxígeno durante la inflamación periodontal.

Effects of elderflower extract enriched with polyphenols on antioxidant defense of salmon leukocytes

BACKGROUND: In fish farming, the plant extracts containing antioxidant compounds have been added to the diet for enhancing pathogen resistance. In vitro studies evaluating the antioxidant effect of herbal extracts on fish cell models have focused on ROS production and the respiratory burst mechanism. However, the effects on enzymatic antioxidant defense on salmon leukocytes have not been evaluated. This study aims to evaluate the enzymatic antioxidant defense and ROS-induced cell damage in Salmon Head Kidney-1 (SHK-1) cell line exposed to polyphenol-enriched extract from Sambucus nigra flowers. RESULTS: Firstly, the Total Reactive Antioxidant Power (TRAP) assay of elderflower polyphenol (EP) was evaluated, showing 459 and 489 times more active than gallic acid and butyl hydroxy toluene (BHT), respectively. The toxic effect of EP on salmon cells was not significant at concentrations below 120 mg/ mL and no hemolysis activity was observed between 20 and 400 mg/mL. The treatment of SHK-1 cell line with EP decreased both the lipid peroxidation and protein oxidation induced by H2O2, which could be associated with decreasing oxidative stress in the SHK-1 cells since the GSH/GSSG ratio increased when only EP was added. CONCLUSIONS: These results suggest that plant extracts enriched with polyphenols could improve the enzymatic antioxidant defense of salmon leukocytes and protect the cells against ROS-induced cell damage

Efecto de la suplementación del medio de incubación con extracto de Berberis microphylla (calafate) sobre la funcionalidad espermática en semen bovino descongelado / Effect of supplementation of incubation medium with Berberis microphylla (calafate) extract on sperm functionality in thawed bovine semen

RESUMEN: En el semen criopreservado, los procesos de congelación/descongelación y posterior manipulación, dañan las células espermáticas provocando disminución de la capacidad fecundante de los espermatozoides descongelados. Estos procesos han sido asociados con el estado de estrés oxidativo (EO) inducido por altos niveles de especies reactivas de oxígeno (EROS), causando daño a la función y estructura espermática. Los espermatozoides descongelados pueden ser protegidos de este daño, con la adición de antioxidantes (AO) al medio de incubación. El fruto de Calafate (Berberis microphylla G. Forst.) posee una alta capacidad antioxidante, lo que hace interesante investigar el efecto de sus componentes antioxidantes en estos procesos biotecnológicos especialmente postdescongelación. El objetivo de este estudio fue determinar el efecto de la suplementación de extracto liofilizado de fruto de Calafate (ELC), sobre la calidad espermática post-descongelación. Previamente se caracterizó el ELC, determinando la actividad antioxidante y metabolitos como fenoles y antocianinas; posteriormente, espermatozoides de bovino descongelados fueron incubados en un medio base suplementado con diferentes concentraciones de ELC. Post-incubación se evaluó la motilidad progresiva; la viabilidad e integridad de la membrana plasmática (SYBR14- PI) y acrosomal (FITC-PNA/PI) y la peroxidación lipídica (BODIPY) por citometría de flujo. La caracterización de ELC demostró que tanto la actividad antioxidante como los fenoles y antocianinas incrementan concomitante con el aumento de la concentración de ELC. La adición de ELC al medio de incubación, dependiendo de la concentración y tiempo de incubación, sería eficaz en proteger la motilidad, viabilidad e integridad de la membrana plasmática y disminuir la lipoperoxidación en los espermatozoides de bovino descongelados.

SUMMARY: In cryopreserved semen, the freezing/thawing process following of manipulation, damage the sperm cell, decreasing the fertilizing capacity of the thawed sperm; being one of the main factors of this damage the oxidative stress. The sperm once thawed can be protected from this damage, with the addition of antioxidants to the incubation medium. The Calafate fruit (Berberis microphylla G. Forst.) has a high antioxidant capacity, making it an interesting resource for investigating the effect of its antioxidant components on biotechnological processes. The objective of this study was to determine the effect of supplementation of Calafate fruit lyophilized extract (ELC) on sperm quality. The lyophilized extract of the Calafate fruit was characterized, determining the antioxidant activity and metabolites such as phenols and anthocyanins; subsequently, thawed bovine sperm were incubated in a medium supplemented with different concentrations of ELC. Post-incubation, progressive motility was evaluated. By flow cytometry, the viability and integrity of the plasma (SYBR14-PI), and acrosomal (FITC-PNA / PI), as well as lipid peroxidation (BODIPY), was determined. The characterization of Calafate fruits lyophilized extract indicated that antioxidant activity, phenols and anthocyanins increased concomitantly with the increase of dose extract used. The addition of ELC to the incubation medium, depending on the concentration and incubation time, would be effective to protect motility, viability and integrity of the plasma membrane and decreased lipid peroxidation in thawed bovine sperm.

Cytotoxicity and underlying mechanism of evodiamine in HepG2 cells / 北京大学学报(医学版)

OBJECTIVE@#To investigate evodiamine (EVO)-induced hepatotoxicity and the underlying mechanism.@*METHODS@#HepG2 cells were treated with EVO (0.04-25 μmol/L) for different time intervals, and the cell survival rate was examined by cell counting kit-8 (CCK-8) method. After HepG2 cells were treated with EVO (0.2, 1 and 5 μmol/L) for 48 h, the alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) activities and total bilirubin (TBIL) content of supernatant were detected. A multifunctional microplate reader was used to detect the intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in HepG2 cells to evaluate the level of cell lipid peroxidation damage. The interactions between EVO and apoptosis, autophagy or ferroptosis-associated proteins were simulated by molecular docking. The HepG2 cells were stained by mitochondrial membrane potential (MMP) fluorescent probe (JC-10) and annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI), and MMP and apoptosis in HepG2 cells were detected by flow cytometry. The protein expression levels of caspase-9, caspase-3, bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were detected by Western blot.@*RESULTS@#The cell survival rate was significantly reduced after the HepG2 cells were exposed to EVO (0.04-25 μmol/L) in a time- and dose-dependent manner. The half maximal inhibitory concentration (IC50) of the HepG2 cells treated with EVO for 24, 48 and 72 h were 85.3, 6.6 and 4.7 μmol/L, respectively. After exposure to EVO (0.2, 1 and 5 μmol/L) for 48 h, the ALT, AST, LDH, ALP activities and TBIL content in the HepG2 cell culture supernatant, and the MDA content in the cells were increased, and SOD enzyme activity was decreased. Molecular docking results showed that EVO interacted with apoptosis-associated proteins (caspase-9 and caspase-3) better. JC-10 and Annexin V-FITC/PI staining assays demonstrated that EVO could decrease MMP and promote apoptosis in the HepG2 cells. Western blot results indicated that the protein expressions of cleaved caspase-9 and cleaved caspase-3 were upregulated in the HepG2 cell treated with EVO for 48 h. In contrast, the protein expressions of pro-caspase-3, BSEP and MRP2 were downregulated.@*CONCLUSION@#These results suggested that 0.2, 1 and 5 μmol/L EVO had the potential hepatotoxicity, and the possible mechanism involved lipid peroxidation damage, cell apoptosis, and cholestasis.

Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis

BACKGROUND: Defective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease. RESULTS: Here, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. Compared to isogenic CFTR corrected cells (C38), the IB3-1 cells showed increased susceptibility to cell death upon exposure to iron in the form of ferric ammonium citrate (FAC) and the ferroptosis inducer, erastin. This phenotype was accompanied by accumulation of intracellular ferrous iron and lipid peroxides and the extracellular release of malondialdehyde, all indicative of redox stress, and increased levels of lactate dehydrogenase in the culture supernatant, indicating enhanced cell injury. The ferric iron chelator defer-oxamine (DFO) and the lipophilic antioxidant ferrostatin-1 inhibited FAC and erastin induced ferroptosis in IB3-1 cells. Glutathione peroxidase 4 (GPX4) expression was decreased in IB3-1 cells treated with FAC and erastin, but was unchanged in C38 AECs. Necroptosis appeared to be involved in the enhanced susceptibility of IB3-1 AECs to ferroptosis, as evidenced by partial cell death rescue with necroptosis inhibitors and enhanced mixed lineage kinase domain-like (MLKL) localisation to the plasma membrane. CONCLUSION: These studies suggest that the increased susceptibility of CF AECs to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defences. In addition, the process of ferroptotic cell death in CF AECs does not appear to be a single entity and for the first time we describe necroptosis as a potential contributory factor. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis.

Biomarker responses of cardiac oxidative stress to high intensity interval training in rats

Abstract Aim: The present study aimed to verify the cardiac oxidative stress biomarker responses to high-intensity interval training (HIIT) in rats. Methods: Sixteen male Wistar rats weighing 250 to 300 g were equally divided into two groups (8 animals/group): sedentary control (SC) and trained group (HIIT). The exercise protocol consisted of high-intensity swimming (14% of body weight, 20 s of activity with 10 s of pause performed 14 times) which was performed for 12 consecutive days. Results: The cardiac tissue concentrations of malondialdehyde and carbonylated proteins showed no significant changes; on the other hand, hydroperoxide levels were higher in the HIIT group than in the SC group. The activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes and the levels of reduced glutathione and sulfhydryl remained unchanged. Conclusion: It is possible to conclude that short-term high-intensity interval training induces changes in the cardiac oxidative stress biomarker but with no effect on the antioxidant enzymes.

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

The metabolic networks of ferroptosis and links to lung diseases / 生理学报

Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.

Aging and low-intensity exercise change oxidative biomarkers in brain regions and radiographic measures of femur of Wistar rats

We investigated changes in oxidative biomarkers in brain regions such as brainstem, cerebellum, and cerebral cortex of 3-, 6-, 18-, 24-, and 30-month-old rats. We also assessed the effects of low-intensity exercise on these biomarkers in these regions of 6-, 18-, and 24-month-old rats that started exercise on a treadmill at 3, 15, and 21 months of age, respectively. Radiographic images of the femur were taken for all rats. A total of 25 rats (age: twelve 6-, ten 18-, ten 24-, and three 30-month-old rats) were used. Lipid hydroperoxide levels increased in cerebellum at 18 months. Total antioxidant activity exhibited lowest values in brainstem at 3 months. Superoxide dismutase activity did not exhibit significant changes during aging. Total thiol content exhibited lowest values in brain regions of 24- and 30-month-old rats. Exercise reduced total thiol content in brainstem at 6 months, but no change occurred in other regions and other ages. Femur increased its length and width and cortical thickness with advancing age. No change occurred in medullary width. Radiolucency increased and sclerosis was found in cortical and medullary bone with advancing age. Exercise reduced radiolucency and medullary sclerosis. Therefore, aging differentially changed oxidative biomarkers in different brain regions and radiographic measures of the femur. Low-intensity exercise only ameliorated some radiographic measurements of femur. Since the present study possessed limitations (small number of rats per group), a beneficial effect of regular low-intensity exercise on oxidative markers in brain cannot be ruled out.

Phenolic compounds profile, neuroprotective effect and antioxidant potential of a commercial Turkish coffee / Perfil do componente fenólico, efeito neuroprotector e potencial antioxidante de um café comercial turco

ABSTRACT Objective The purpose of this study is to determine the phenolic and flavonoid contents, and antioxidant activities and neuroprotective effects of powdered coffee sample of a commercial coffee brand originated from Sivas, Turkey. Methods Total phenolic, flavonoid and antioxidant contents, enzymatic and non-enzymatic antioxidative activities based on 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity, metal chelating potential, reducing power, superoxide dismutase and catalase activity tests and lipid peroxidation inhibition potentials of the ethanolic and aqueous extracts of the coffee sample were assayed using the commonly preferred spectrophotometric methods. Furthermore the extracts' cholinesterase and tyrosinase inhibition potentials were evaluated. Phenolic profiles of the coffee sample were investigated using high performance liquid chromatography. Results Catechin was the most frequently detected phenolic acid. In addition, it was demonstrated that the water extract has a significant impact when compared with standard antioxidants. While the SC50 (sufficient concentration to obtain 50% of a maximum scavenging capacity) value for the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl free radical was calculated as being 0.08mg/mL for water extract, the amount of chelating agents with half Fe2+ ions in the medium was found to be 0.271mg/mL. Additionally, it was shown that 0.1mg/mL concentration of both extracts prevents lipid peroxidation by 8%. Compared with standard drugs, inhibition potentials of cholinesterase and tyrosinase enzymes were considered as moderately acceptable in these samples. Conclusion Besides the extracts' enzymatic antioxidant activity, their inhibition potential on cholinesterase and tyrosinase enzymes - which are important clinical enzymes - reveal that this natural source can be used as a valuable resource in different fields, especially in medicine.

RESUMO Objetivo O objetivo deste estudo é determinar o conteúdo fenólico e flavonoide, bem como as atividades antioxidantes e os efeitos neuroprotetores de uma amostra de café em pó de uma promissora marca comercial proveniente de Sivas, Turquia. Métodos A partir dos métodos espectrofotométricos comumente utilizados, foram analisados os seguintes aspectos da amostra de café: teores de fenólicos totais, flavonoides e antioxidantes; atividades antioxidantes enzimáticas e não enzimáticas, baseadas na atividade de eliminação de radicais livres de 2,2-difenil-1-picrilhidrazila potencial quelante de metais; poder redutor; testes de atividade de superóxido dismutase e catalase; e potenciais de inibição da peroxidação lipídica dos extratos etanólicos e aquosos. Além disso, foram avaliados os potenciais de inibição da colinesterase e da tirosinase dos extratos. Os perfis fenólicos da amostra de café foram investigados por cromatografia líquida de alta eficiência. Resultados Entre os ácidos fenólicos estudados, o mais detectado foi a catequina. Especialmente, foi demonstrado que o extrato de água tem um impacto significativo quando comparado com os antioxidantes padrão. Determinou--se que o valor de SC50 (a concentração suficiente para obter 50% da capacidade máxima de eliminação) da atividade de eliminação do radical 2,2-difenil-1-picrilhidrazilab/para extrato de água era de 0,08mg/mL, enquanto a quantidade de agentes quelantes com metade de Fe2+ íons na média foi encontrada como 0,271mg/mL. Também foi demonstrado que a concentração de 0,1mg/mL de ambos os extratos inibe a peroxidação lipídica em cerca de 8%. Comparado com drogas padrão, os potenciais de inibição das amostras nas enzimas e tirosinase foram aceitáveis como moderados. Conclusão Os resultados mostram que, além de terem atividade antioxidante enzimática, os extratos apresentam potencial de inibição das enzimas colinesterase e tirosinase, que são importantes enzimas clínicas, o que revela que essa fonte natural pode ser usada como um recurso valioso em vários campos, principalmente na medicina.