Investigation of the protective effect of boric acid against hepatotoxic and nephrotoxic injury induced by acrylamide in rats / Investigación del efecto protector del ácido bórico contra lesiones hepatotóxicas y nefrotóxicas inducidas por acrilamida en ratas

SUMMARY: To investigate if the administration of boric acid (BA) would exert any protective effect against possible nephrotoxicity and hepatotoxicity induced by the exposure to acrylamide (ACR) in rats. In our study, we used a total of 28 rats that were divided into four equal groups. Group 1: the control group which was not treated with any procedure. Group 2: the ACR group that was administered ACR 50 mg/kg/day via intraperitoneal (i.p) route for 14 days. Group 3: the BA group that was administered BA 200 mg/kg/ day via gavage via peroral (p.o) route for 14 days. Group 4: the ACR+BA group that was administered BA simultaneously with ACR. Total antioxidant and oxidant (TAS/TOS) capacities were measured in all groups at the end of the experiment. In addition, the specimens obtained were evaluated with histopathological examination. Studies showed that the ACR and ACr+BA groups were not significantly different in terms of hepatic TAS level while the TOS level was higher in the ACR group than the ACR+BA group. The groups did not show any significant difference regarding renal TAS and TOS levels. In the histopathological examination of the hepatic tissue, the histopathological injury score of the ACR group was significantly higher than those of the other groups whereas it was significantly lower in the ACR+BA group than the ACR group. Our study concluded that Boric acid had a protective effect against acrylamide- induced hepatotoxicity, but not against nephrotoxicity.

El objetivo de este estudio fue investigar si la administración de ácido bórico (BA) ejercería algún efecto protector frente a la posible nefrotoxicidad y hepatotoxicidad inducida por la exposición a acrilamida (ACR) en ratas. En nuestro estudio, utilizamos un total de 28 ratas que se dividieron en cuatro grupos iguales. Grupo 1: grupo control que no fue tratado. Grupo 2: grupo ACR al que se le administró ACR 50 mg/kg/día por vía intraperitoneal (i.p) durante 14 días. Grupo 3: grupo BA al que se le administró BA 200 mg/kg/día por sonda por vía peroral (p.o) durante 14 días. Grupo 4: grupo ACR+BA al que se administró BA simultáneamente con ACR. Las capacidades antioxidantes y oxidantes totales (TAS/TOS) se midieron en todos los grupos al final del experimento. Además, los especímenes obtenidos fueron evaluados con examen histopatológico. Los estudios demostraron que los grupos ACR y ACr+BA no fueron significativamente diferentes en términos del nivel hepático de TAS, mientras que el nivel de TOS fue mayor en el grupo ACR que en el grupo ACR+BA. Los grupos no mostraron ninguna diferencia significativa con respecto a los niveles renales de TAS y TOS. En el examen histopatológico del tejido hepático, la puntuación de lesión histopatológica del grupo ACR fue significativamente mayor que la de los otros grupos, mientras que fue significativamente menor en el grupo ACR+BA que en el grupo ACR. Nuestro estudio concluyó que el ácido bórico tiene un efecto protector contra la hepatotoxicidad inducida por acrilamida, pero no contra la nefrotoxicidad.

Adult Rat Liver After Subchronic Acrylamide Treatment: Histological, Stereological and Biochemical Study

SUMMARY: Acrylamide (AA) is a widely used chemical and an important monomer in various industrial and laboratory processes. In addition, AA is formed during processing of starchy food at high temperature. The aim of our study was to examine effects of subchronic AA treatment on adult rat liver using histological, stereological and biochemical methods. Adult male Wistar rats were treated with AA at doses of 25 mg/kg b.w. and 50 mg/kg b.w. for three weeks. Stereological analysis showed decrease of volume density of hepatocyte cytoplasm, and increase of volume density of hepatocyte nuclei and nucleocytoplasmic ratio in AA50mg group. Immunohistochemical analysis of the liver sections showed that treatment with AA50mg increase the percentage of PCNA positive cells, while the percentage of caspase 3 positive cells was not affected by AA. PAS-staining showed that glycogen content in hepatocytes was not affected by AA. Serological examination revealed increase of lipid peroxidation in AA50mg group, while total protein concentration, protein thiol group level, as well as, paraoxonase 1 activity were not changed in AA-exposed animals. Stereological and immunohistochemical analyses of adult liver sections suggest increase of proliferation in AA50mg group, while increase of lipid peroxidation in serum of AA50mg group indicates oxidative stress induction.

La acrilamida (AA) es un químico ampliamente utilizado y un monómero importante en varios procesos industriales y de laboratorio. Además, la AA se forma durante el procesamiento de alimentos ricos en almidón a altas temperaturas. El objetivo de nuestro estudio fue examinar los efectos del tratamiento con AA subcrónica en el hígado de rata adulta utilizando métodos histológicos, estereológicos y bioquímicos. Se trataron ratas Wistar macho adultas con AA a dosis de 25 mg/kg p.v. y 50 mg/kg de peso corporal por tres semanas. El análisis estereológico mostró una disminución de la densidad del volumen del citoplasma de los hepatocitos y un aumento de la densidad del volumen de los núcleos de los hepatocitos y la relación nucleocitoplasmática en el grupo de 50 mg de AA. El análisis inmunohistoquímico de las secciones de hígado mostró que el tratamiento con 50 mg de AA aumentó el porcentaje de células positivas para PCNA, mientras que el porcentaje de células positivas para caspasa 3 no se vio afectado por AA. La tinción con PAS mostró que el contenido de glucógeno en los hepatocitos no se vio afectado por AA. El examen serológico reveló un aumento de la peroxidación de lípidos en el grupo de 50 mg de AA, mientras que la concentración de proteína total, el nivel del grupo tiol de proteína y la actividad de paraoxonasa 1 no cambiaron en los animales expuestos a AA. Los análisis estereológicos e inmunohistoquímicos de secciones de hígado adulto sugieren un aumento de la proliferación en el grupo AA50 mg, mientras que el aumento de la peroxidación lipídica en suero del grupo AA50 mg indica inducción de estrés oxidativo.

The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats

Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1ß, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties

The preventive effect of taxifolin on acrylamide-induced heart damage in rats / O efeito preventivo da taxifolina em danos cardíacos induzidos por acrilamida em ratos

ABSTRACT Objective Acrylamide is a toxic compound widely used in industrial sectors. Acrylamide causes reactive oxygen species formation and the subsequent lipid peroxidation reaction, which plays an important role in the pathogenesis of oxidative damage. Taxifolin is a flavonoid with antioxidant properties that inhibit reactive oxygen species formation. In this study, we aimed to investigate the preventive effect of taxifolin on acrylamide-induced oxidative heart damage. Methods The rats were divided into three groups: Acrylamide, Acrylamide+Taxifolin , and Healthy group. Water and food intake and body weight alterations were recorded daily. Malondialdehyde, total glutathione, nuclear factor kappa-B, total oxidant status, and total antioxidant status levels were analyzed from the heart tissue. Troponin-I levels, the parameter known as a cardiac biomarker, were analyzed from the blood sample. The cardiac histopathologic examination was also performed. Results In the Acrylamide group animals, the malondialdehyde, nuclear factor kappa-B, total oxidant status, and troponin-I levels were significantly higher compared to the ones of Acrylamide+Taxifolin and Healthy groups. The levels of total glutathione and total antioxidant status were significantly lower compared to Acrylamide+Taxifolin and Healthy groups'. Additionally, in the Acrylamide group, body weight gain, food and water intake, significantly declined compared to the Acrylamide+Taxifolin and Healthy groups. However, in the Acrylamide+Taxifolin group, taxifolin supplementation brought these values close to Healthy group ones. Furthermore, taxifolin treatment ameliorated structural myocardial damage signs induced by acrylamide. Conclusion Acrylamide exposure significantly induced oxidative damage to rat heart tissue. Taxifolin was able to improve the toxic consequences of acrylamide biochemically and histopathologically, possibly due to its antioxidant properties.

RESUMO Objetivo A acrilamida é um composto tóxico amplamente utilizado em setores industriais. Ela causa a formação de reativas de oxigênio e subsequente reação de peroxidação lipídica, que desempenham um papel importante na patogênese do dano oxidativo. A taxifolina é um flavonóide com propriedades antioxidantes que inibe a formação de reativas de oxigênio. Neste estudo, o objetivo foi investigar o efeito preventivo da taxifolina no dano cardíaco oxidativo induzido por acrilamida. Métodos Os ratos foram divididos em três grupos: Acrilamida, Acrilamida+Taxifolina e grupo Saudável. Ingestão de água e comida e alterações de peso corporal dos animais foram registradas diariamente. Malondialdeído, glutationa total, fator nuclear kappa-B, estado oxidante total e estado antioxidante total foram analisados no tecido cardíaco dos ratos. Os níveis de troponina-I, - parâmetro conhecido como biomarcador cardíaco, foram analisados a partir de amostra de sangue. Um exame histopatológico cardíaco também foi realizado. Resultados Nos animais do grupo Acrilamida, os níveis de malondialdeído, fator nuclear kappa-B, estado oxidante total e troponina-I foram significativamente maiores em comparação com os do grupo Acrilamida+Taxifolina e Saudável. Os níveis de glutationa total e estado antioxidante total foram significativamente mais baixos em comparação com grupos Acrilamida+Taxifolina e Saudável. Além disso, no grupo Acrilamida, o ganho de peso corporal e a ingestão de alimentos e água diminuíram significativamente em comparação com os animais dos grupos Acrilamida+Taxifolina e Saudável. No entanto, no grupo Acrilamida+Taxifolina, a suplementação com taxifolina aproximou esses valores aos do grupo Saudável. Além disso, o tratamento com taxifolina melhorou os sinais de dano miocárdico estrutural induzidos pela acrilamida. Conclusão A exposição à acrilamida induziu significativamente o dano oxidativo do tecido cardíaco dos ratos. A taxifolina foi capaz de melhorar as consequências tóxicas da acrilamida bioquímica e histopatologicamente, possivelmente devido às suas propriedades antioxidantes.

Effects of acute oral exposure to acrylamide on histological structures of the stomach in Wistar rats / Efectos de la exposición oral aguda a la acrilamida sobre las estructuras histológicas del estómago en ratas Wistar

SUMMARY: Acrylamide is a toxic chemical substance with wide implementation in chemical industry. In 2002 the presence of acrylamide was discovered in foods rich in starch which are prepared at high temperatures. The aim of this study was to investigate the histopathological changes in the gastric tissue in Wistar rats induced with injection of oral acrylamide. The research was carried out 6 groups of 5 animals (Wistar rats), two control groups and four experimental groups. Histological changes in the stomach tissue of Wistar rats are seen as a direct slight damage of the surface epithelium, accompanynig inflammatory reaction and renewal of the epithelium. Examined inflammatory and degenerative parameters show a positive correlation with respect to dose and time of exposition to acrylamide. Knowing the mechanism of action of these toxic substances, allows to apply adequate prevention in nutrition and make an appropriate choice of therapeutic methods.

RESUMEN: La acrilamida es una sustancia química tóxica con amplia aplicación en la industria química. En el año 2002 se determinó la presencia de acrilamida en alimentos ricos en almidón preparados a altas temperaturas. El objetivo de este estudio fue investigar los cambios histopatológicos en el tejido gástrico en ratas Wistar inducidos con inyección de acrilamida oral. La investigación se llevó a cabo en 6 grupos de 5 animales, dos grupos control y cuatro grupos experimentales. Los cambios histológicos en el tejido del estómago de las ratas Wistar se ven como un ligero daño directo del epitelio superficial, que acompaña a la reacción inflamatoria y la renovación del epitelio. Los parámetros inflamatorios y degenerativos examinados muestran una correlación positiva con respecto a la dosis y el tiempo de exposición a la acrilamida. El conocimiento del mecanismo de acción de estas sustancias tóxicas permite aplicar una prevención adecuada en nutrición y hacer una elección oportuna de los métodos terapéuticos.

Effects of site-directed PEGylation on L-asparaginase thermostability / Efeitos da PEGuilação sítio-dirigida na termoestabilidade da L-asparaginase

The enzyme L-asparaginase (ASNase) is broadly applied as a drug to treat acute lymphoblastic leukemia, as well as in the food industry to avoid acrylamide formation in baked and fried food. In the present work, ASNase was covalently attached to polyethylene glycol (PEG) of different molecular weights (ASNase-PEG-5, ASNase-PEG-10, ASNase-PEG-20, and ASNase-PEG-40) at the N-terminal portion (monoPEGylation). Native and PEGylated forms were analyzed regarding thermodynamics and thermostability based on enzyme activity measurements. ASNase (native and PEGylated) presented maximum activity at 40 °C and denaturation followed a first-order kinetics. Based on these results, the activation energy for denaturation (E*d) was estimated and higher values were observed for PEGylated forms compared to the native ASNase, highlighting the ASNase-PEG10 with a 4.24-fold increase (48.85 kJ.mol-1) in comparison to the native form (11.52 kJ.mol-1). The enzymes were evaluated by residual activity over time (21 days) under different storage temperatures (4 and 37 °C) and the PEGylated conjugates remained stable after the 21 days. Thermodynamic parameters like enthalpy (ΔH‡), entropy (ΔS‡) and Gibbs free energy (ΔG‡) of ASNase (native and PEGylated) irreversible denaturation were also investigated. Higher - and positive - values of Gibbs free energy were found for the PEGylated conjugates (61.21 a 63.45 kJ.mol-1), indicating that the process of denaturation was not spontaneous. Enthalpy also was higher for PEGylated conjugates (18.84 a 46.08 kJ.mol-1), demonstrating the protective role of PEGylation. As for entropy, the negative values were more elevated for native ASNase (-0.149 J/mol.K), pointing out that the denaturation process enhanced the randomness and aggregation of the system, which was observed by circular dichroism. Thus, PEGylation proved its potential to increase ASNase thermostability

A enzima L-asparaginase (ASNase) é amplamente usada como medicamento para tratamento da leucemia linfoblástica aguda, bem como na indústria de alimentos para evitar a formação de acrilamida em alimentos cozidos e fritos. No presente trabalho, ASNase foi covalentemente ligada ao polímero poli(etilenoglicol) (PEG) de diferentes massas moleculares (ASNase-PEG-5, ASNase-PEG- 10, ASNase-PEG-20, and ASNase-PEG-40) na região N-terminal (monoPEGuilação) a fim de se estudar os efeitos da PEGuilação na termoestabilidade da enzima. As formas PEGuiladas e nativa foram analisadas em relação à termodinâmica e termoestabilidade a partir de atividade enzimática. A ASNase (nativa e PEGuilada) apresentou atividade máxima a 40 °C e a desnaturação ocorreu por cinética de primeira ordem. Com base nesses resultados, a energia de ativação para desnaturação (E*d) foi estimada e maiores valores foram observados para as formas PEGuiladas em comparação à enzima nativa, destacando-se a ASNase-PEG10 com aumento de 4.24 vezes (48.85 kJ.mol-1) em comparação com a forma nativa in (11.52 kJ.mol mol-1). As enzimas foram avaliadas por sua atividade residual ao longo do tempo em diferentes temperaturas de armazenamento (4 e 37 °C) e os conjugados PEGuilados mostraram-se mais estáveis após os 21 dias de ensaio. Parâmetros termodinâmicos como entalpia (ΔH‡) de desnaturação irreversível foram analisados. Valores maiores - e ), entropia (ΔS‡) de desnaturação irreversível foram analisados. Valores maiores - e ) e energia livre de Gibbs (ΔG‡) de desnaturação irreversível foram analisados. Valores maiores - e positivos - da energia livre de Gibbs foram encontrados para os conjugados PEGuilados (61.21 a 63.45 kJ.mol-1), indicando que o processo de desnaturação não ocorreu de forma espontânea. A entalpia também foi maior para os conjugados PEGuilados (18.84 a 46.08 kJ.mol-1), demonstrando o efeito protetivo da PEGuilação. Já para a entropia, os valores negativos foram mais elevados para a ASNase nativa (-0.149 J/mol.K), apontando que o processo de desnaturação aumentou a aleatoriedade e agregação do sistema, o que foi confirmado pelo dicroísmo circular. Dessa forma, a PEGuilação revelou o seu potencial de aumento de termoestabilidade para a ASNase

Role of ascorbic acid versus silymarin in amelioration of hepatotoxicity induced by acrylamide in adult male albino rats: histological and immunohistochemical study / Rol del ácido ascórbico frente a la silimarina en la mejoría de la hepatotoxicidad inducida por acrilamida en ratas albinas macho adultas: estudio histológico e inmunohistoquímico

SUMMARY: Acrylamide (ACR) is a cytotoxic and carcinogenic material. It is a product of a Maillard reaction during the cooking of many types of fried fast food, e.g. potato chip fries, and chicken nuggets. ACR has a severe toxic effect on different body organs. This study investigates the hepatotoxic effect of ACR, and the protective effect of ascorbic acid and silymarin. For this purpose, forty adult, male, albino rats were divided into four groups and received the following treatments for fourteen days: Group I: (the control) normal saline; Group II: ACR only; Group III: ACR and ascorbic acid; and Group IV: ACR and silymarin. Under a light microscope, the liver from rats treated with ACR only presented disturbed liver architecture, degenerated hepatocytes, reduced glycogen contents, congested central vein, and increased collagen fibres with areas of fibrosis. Immunohistochemical examination revealed an increased mean number of CD68-, and α-SMA-positive cells. This indicates the presence of large numbers of stellate macrophages (Kupffer cells) and Hepatic stellate cells (HSCs). The combination of ACR with either ascorbic acid or silymarin resulted in less hepatic degeneration, less fibrosis and fewer CD68 and α-SMA positive cells compared to the ACR only group. In conclusion, treatment with silymarin or ascorbic acid along with ACR appears to alleviate ACR-induced hepatotoxicity with more protection in silymarin treated rats.

RESUMEN: La acrilamida (ACR) es un material citotóxico y cancerígeno. Es producto de la reacción de Maillard durante la cocción de muchos tipos de comida rápida y frita, por ejemplo: papas fritas y nuggets de pollo. ACR tiene un efecto tóxico severo en diferentes órganos del cuerpo. Este estudio investigó el efecto hepatotóxico del ACR y el efecto protector del ácido ascórbico y la silimarina. Con este fin, cuarenta ratas albinas machos adultas se dividieron en cuatro grupos y recibieron los siguientes tratamientos durante catorce días: Grupo I (control), solución salina normal; Grupo II, solo ACR; Grupo III, ACR y ácido ascórbico; y Grupo IV, ACR y silimarina. Bajo microscopio óptico, el hígado de ratas tratadas con ACR solo presentó alteración de su arquitectura, entre ellos hepatocitos degenerados, contenido reducido de glucógeno, vena central congestionada y aumento de fibras de colágeno con áreas de fibrosis. El examen inmunohistoquímico reveló un aumento del número medio de células CD68 y α-SMA positivas. Esto indica la presencia de un gran número de macrófagos estrellados (células de Kupffer) y células estrelladas hepáticas (HSC). La combinación de ACR con ácido ascórbico o silimarina resultó en menos degeneración hepática, menos fibrosis y menos células positivas para CD68 y α-SMA en comparación con el grupo de ACR solo. En conclusión, el tratamiento con silimarina o ácido ascórbico junto con ACR parece aliviar la hepatotoxicidad inducida por ACR.

Acrylamide reduces plasma antioxidant vitamin levels in rats due to increased oxidative damage / Acrilamida reduz os níveis de vitamina antioxidante no plasma em ratos devido ao aumento do dano oxidativo

ABSTRACT Objective Acrylamide is a potentially neurotoxic and carcinogenic chemical and naturally creates during the heating process of carbohydrate-rich foods, such as potato chips and breakfast cereals. Acrylamide might be ingested by people via consuming food that contains it. Therefore, we investigated the effect of acrylamidegiven orally to male and female rats on plasma retinoic acid and α-tocopherol and serum sialic acid and malondialdehyde levels. Method A total of 50 Wistar rats were used (25 female and 25 male, three-four weeks old). The rats of each sex were given 2 and 5mg/kg/day acrylamide via drinking water for 90 days. At the end of the treatment, the animals were euthanized by cervical dislocation. Blood specimens were collected through cardiac puncture, and serum and plasma samples were analysed using the high-performance liquid chromatography technique with a Ultraviolet detector. Results The analysis of the plasma and serum samples revealed that serum sialic acid and malondialdehyde levels in both sexes given 5mg/kg/day acrylamide were significantly increased, and the serum sialic acid levels were higher in female rats given 2mg/kg/day acrylamide. The plasma retinoic acid and α-tocopherol levels significantly decreased in both sexes given only the highest dose. Conclusion The results show that acrylamide causes an increase in oxidative stress and leads to a decrease in the levels of retinoic acid and α-tocopherol which play a role in the defense mechanism against this stress.

RESUMO Objetivo A acrilamida é um químico potencialmente neurotóxico e carcinogênico, sendo naturalmente criada durante o processo de aquecimento de alimentos ricos em carboidratos, como batatas fritas e cereais matinais. Dado que o composto pode ser ingerido através do consumo de alimentos, o presente trabalho teve por objetivo investigar o seu efeito, quando administrado oralmente a ratos, medindo-se os níveis plasmáticos de ácido retinoico e α-tocoferol, bem como os níveis séricos de ácido siálico e malondialdeído Métodos Foram utilizados cinquenta ratos Wistar, sendo metade de cada sexo, com idade entre três e quatro semanas. Os animais foram divididos em dois grupos, os quais receberam diferentes doses diárias de acrilamida, via água potável, durante noventa dias: o primeiro ingeriu 2mg/kg/dia; e o segundo, 5mg/kg/dia. Ao final do tratamento, os animais foram eutanasiados por meio de luxação cervical. Amostras de sangue foram coletadas através de punção cardíaca, assim como amostras de soro e plasma foram medidas usando-se a técnica de cromatografia líquida de alta performance com detector de Ultravioleta. Resultados A análise das amostras de plasma e soro revelou que os níveis de ácido siálico e malondialdeído, em ratos de ambos os sexos tratados com acrilamida de 5mg/kg/dia, foram significativamente aumentados, ao passo que os níveis séricos de ácido siálico foram maiores em ratas tratadas com 2mg/kg/dia de acrilamida. Já os níveis plasmáticos de ácido retinoico e α-tocoferol diminuíram significativamente em ratos de ambos os sexos, quando tratados com a dose mais elevada.Concl Conclusão Os resultados mostram que a acrilamida causa um aumento no estresse oxidativo e leva a uma diminuição nos níveis de ácido retinoico e α-tocoferol, que desempenham um papel no mecanismo de defesa contra esse estresse.

FxClear, A Free-hydrogel Electrophoretic Tissue Clearing Method for Rapid De-lipidation of Tissues with High Preservation of Immunoreactivity

Over the last two decades, several tissue clearing methodologies have been established that render tissues optically transparent and allow imaging of unsectioned tissues of significant volumes, thus improving the capacity to study the relationships between cell and 3D tissue architecture. Despite these technical advances, the important unsolved challenges that these methods face include complexity, time, consistency of tissue size before and after clearing, and ability to immunolabel various antibodies in cleared tissue. Here, we established very simple and fast tissue clearing protocol, FxClear, which involves acrylamide-free electrophoretic tissue clearing (ETC). By removal of the acrylamide infusion step, we were able to achieve fast reaction time, smaller tissue expansion, and higher immunoreactivity. Especially, immunoreactivity and fluorescence intensity were increased in FxClear-processed tissues compared to un-cleared tissues. Our protocol may be suitable for small-sized biopsy samples for 3D pathological examinations.

The effects of monomers used in polymeric biomaterials on renal tissue / Efectos de los monómeros de los biomateriales poliméricos utilizados en tejido renal

SUMMARY: Biomaterials are mostly polymers and are used in artificial organ production in contemporary medicine. They are prepared by the polymerization reaction of many monomers. There are many monomers used in biomaterial production. In this study, we investigated whether acrylamide (AAm), methacrylamide (MAAm), N-isopropylacrylamide (NIPAm) and acrylic acid (AAc) used in polymeric biomaterial production had histopathological effects on renal tissue. In the present study, Wistar albino rats weighing ~ 250-300 g were used. Following the intramuscular injections of 1 mL aqueous monomer solutions at 50 mg/kg concentrations, acrylamide group animals were sacrificed at 1st, 2nd and 3rd weeks, the other monomer group animals were sacrificed at 1st, 2nd, 4th and 6th weeks. One mL serum physiologic were injected intramuscularly to the control group animals at the same time intervals with the experimental group animals. After histological follow-up, serial sections were prepared for evaluation under light microscope. In addition, the diameters of glomeruli and glomeruli space (Bowman's space) are measured, and the changes of the values of all groups with the exposure time were investigated. Acrylamide and its derivatives cause glomerular, arteriolar and tubule interstitial damage in the renal tissue. The narrowing glomeruli space, increasing diffuse mesangial matrix and tubular dilation was observed in some groups. In addition, dilatation, dissociation of tubular epithelium, thickening basement membranes and glycogenic vacuolization was also noted. These adverse results may be due to residual monomer. There should be no monomer residue in the polymer used as biomaterials.

RESUMEN: Los biomateriales en su mayoría son polímeros utilizados en la producción de órganos artificiales en la medicina contemporánea. Éstos son preparados mediante la reacción de polimerización de varios monómeros. Existe una gran cantidad de monómeros usados en la producción de biomateriales. En este estudio se investigó si la acrilamida (AAm), la metacrilamida (MAAm), la N-isopropilacrilamida (NIPAm) y el ácido acrílico (AAc) utilizados en la producción de biomateriales poliméricos tuvieron efectos histopatológicos en el tejido renal. En el presente estudio, se utilizaron ratas Wistar albinas que pesaban 250-300 g. Después de las inyecciones intramusculares (1 ml) de soluciones acuosas de monómero a concentraciones de 50 mg / kg, los animales del grupo de la acrilamida se sacrificaron a la 1ª, 2ª y 3ª semanas, los otros animales del grupo monómero se sacrificaron a las 1ª, 2ª, 4ª y 6ª semanas. Se inyectaron intramuscularmente 1 ml de suero fisiológico a los animales del grupo control en los mismos intervalos de tiempo que los animales del grupo experimental. Después del análisis histológico, se prepararon secciones en serie para su evaluación bajo microscopio óptico. Además, se midieron los diámetros de los glomérulos y el espacio glomerular, y se investigaron los cambios de los valores de todos los grupos con el tiempo de exposición. La acrilamida y sus derivados causaron daño intersticial glomerular, arteriolar y tubular en el tejido renal. El estrechamiento del espacio de los glomérulos, el aumento de la matriz mesangial difusa y la dilatación tubular se observó en algunos grupos. Además, también se observó dilatación, disociación del epitelio tubular, membranas basales espesantes y vacuolización glicogénica. Estos resultados adversos pueden deberse al monómero residual. No debe haber residuo de monómero en el polímero utilizado como biomateriales.

Bioethanol production with different dosages of the commercial Acrylamide polymer compared to a Bioextract in clarifying sugarcane juice

ABSTRACT One of the most important steps is to clarify the juice, which are added synthetic polymer acrylamide base, aiming the fast settling of impurities present in the juice. However, this input is expensive and may have carcinogenic and neurotoxic actions to humans. The search for new natural flocculants that have similarity with the commercial product is of great value. A bioextract that may be promising and has coagulant action is the Moringa oleifera Lam. In this context, the objective of the research was to evaluate the consequences of the use of moringa seed extracts and various concentrations of commercial polymer, such as sedimentation aids in clarifying sugarcane juice in the ethanol production, comparing the efficiency of the bioextract moringa. In the treatment of the juice, excessive addition of flocculants can result in reduction of sugars. The bioflocculant moringa was similar in technological features and the fermentative viability compared to usual dose of commercial polymer in Brazil. The fermentation efficiency was also higher for this flocculant, followed by moringa extract. The results obtained in this research indicate potential to the moringa bioextract, particularly in countries where the doses of flocculants are higher than 5 mg.L-1.

Acrylamide-induced Subacute Neurotoxic Effects on the Cerebral Cortex and Cerebellum at the Synapse Level in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats.</p><p><b>METHODS</b>Thirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated.</p><p><b>RESULTS</b>The 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals (P < 0.05). Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group (P < 0.05). Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool (RRP) was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups.</p><p><b>CONCLUSION</b>Subacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.</p>

Dermal and neural toxicity caused by acrylamide exposure in two Korean grouting workers: a case report

BACKGROUND: Peripheral neuritis caused by acrylamide is well-known, and many Korean grouting workers are frequently exposed to acrylamide in grouting agents that are injected into cracked concrete. We recently encountered two cases of dermal and neural toxicity in Korean grouting workers with exposure to grouting agents that contained a high concentration of acrylamide. CASE PRESENTATION: The first case involved a 44-year-old man with 8 years of waterproofing experience. The patient developed peeling skin on both hands while grouting, which progressed to systemic neurological symptoms, such as reduced sensory function and strength. The patient was diagnosed with peripheral neuropathy caused by acrylamide exposure, and fully recovered after conservative treatment and withdrawal of exposure to the grouting agent. The second case involved a 34-year-old man with 10 years of grouting experience. The patient initially experienced weakness in both legs, which progressed to weakness in his arms and uncontrolled phonation. After being hospitalized, he was diagnosed with cerebellar ataxia and peripheral neuropathy caused by acrylamide exposure, and was discharged after conservative treatment. Our follow-up investigation revealed that both workers were recently exposed to grouting agents that contained higher concentrations of acrylamide, compared to the agents that they had previously been using. CONCLUSIONS: Both workers had workplace acrylamide exposure through dermal contact plus inhalation of dust and vapor, which led to the neural toxicity and dermatitis. Therefore, government studies are needed to investigate the current status of workplace acrylamide use, and to protect workers from the hazardous effects of using acrylamide-containing grouting agents.

The antagonistic effect and mechanism of N-acetylcysteine on acrylamide-induced hepatic and renal toxicity / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>The aim of this study is to investigate hepatic and renal toxicity of acrylamide (ACR) , the antagonistic effect and possible mechanism of N-acetylcysteine (NAC) on the toxicity.</p><p><b>METHODS</b>Forty female SD rats were randomly divided into four groups. All the rats were administrated by intraperitoneal(i.p.) injection and 1.5 hours later by gavage. The control group was administrated with 0.9% NaCl by i.p. injection and gavaged with 0.9% NaCl. The NAC group was administrated with 200 mg/kg NAC by injection and gavaged with 0.9% NaCl. The ACR group was administrated with 0.9% NaCl by injection and gavaged with 40 mg/kg ACR. The combined treatment group was administrated with 200 mg/kg NAC by i.p. injection and gavaged with 40 mg/kg ACR. The rats were administrated once a day for 2 weeks. After 24 hours of the last administration, the rats were decapitated. The blood was collected, the liver and kidney were separated. The body weight, organ coefficient and serum biochemical parameters were measured, and the pathological changes of the tissues were examined with a microscope. Then the expression of NF-κB p65, IκB-α and COX-2 were detected by Western blot.</p><p><b>RESULTS</b>From the second day to the end of the exposure, the body weight of rats in the ACR group was statistically lower than that in the control group (P<0.05) . Compared with the combined treatment group, the body weight in the ACR group statistically decreased in the second and third days (P < 0.05) . The liver and kidney organ coefficients in the ACR group were (4.159%±.371%) and (0.764%±0.068%) respectively, which increased statistically when compared with the control group (P < 0.05) . The contents of ALT, AST and Cr in the serum in the ACR group were (77.370±16.397) U/L、(379.410±57.817) U/L and (77.812±6.391) μmol/L respectively, which were not significantly different with those in the control group and the combined treatment group (P>0.05) . The content of BUN in the serum in the ACR group was (7.005±1.009) mmol/L, which was statistically higher than that in the control group (P<0.05) . Histopathology results showed unclear boundary and nucleus pyknosis in hepatocytes, loose and disordered structures of hepatic cords in the ACR group, but no obvious pathology changes were observed in the kidneys of each group. In the Western blot results, the expression of nuclear NF-κB p65 and COX-2 in the liver in the ACR group was statistically higher than that in the control group and the combined treatment group (P<0.05) , and the expression of IκB-α in the liver in the ACR group statistically decreased compared with the control group and the combined treatment group (P<0.05) . The expression of total NF-κB p65 in the liver in the ACR group was statistically higher than that in the control group (P<0.05) .</p><p><b>CONCLUSION</b>Under the conditions of this experiment, ACR may induce hepatic toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the hepatic toxicity of ACR by inhibiting the NF-κB signaling pathway, whereas the toxic effect of ACR on kidney needs to be further studied.</p>

Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study / 대한해부학회지

The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord.

Effect of curcumin administration against some biochemical alteration induced by acrylamide in adult male albino rats

Acrylamide is a chemical used in many industries, found in carbohydrate rich foods cooked at high temperature. Although it is found to be harmful, human are exposed to varying amounts of it in the diet, especially fried food. Curcumin is a herbal agent used in medicine and proved to be protective against many harmful agents. This study was undertaken to assess the protective effect of curcumin against some biochemical alteration induced by acrylamide in male albino rats. The experimental rats were divided into four groups included a control group, a group treated orally with curcumin by supercritical fluid extractor for 30 days, a group treated orally with acrylamide and a group treated orally with curcumin + acrylamide for 30 days. The results indicated that treatment with ACR alone resulted in a significant decrease in the haematological parameters, triglycerides, insulin, creatine kinase and choline esterase while the concentrations of urea, creatinine, ALT, AST and alkaline phosphatase were increased. Treatment with curcumin during ACR treatment reduced the effects induced by ACR, It could be concluded that curcumin exhibited a protective action against ACR-induced biochemical alterations in rats. For this reason, curcumin is recommended to be used in cooked food due to its palatable taste and prophylactic effect

The Role of NF mRNA and Calpain in NF Reduction of Acrylamide Neuropathy / 生物医学与环境科学（英文）

The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p. every other day with ACR (20 mg/kg·bW or 40 mg/kg·bW) for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and μ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF (NF-L) protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of ACR neuropathy.

Histological study on the possible protective action of ginseng on the injurious effect induced by acrylamide on the midbrain in adult male albino rat

Acrylamide is a synthetic chemical compound commonly used in many branches of industry. Researchers have found acrylamide in certain foods that were heated to a temperature above 120[degree]C. Ginseng is a widely used herbal medicine with numerous beneficial effects. Ginseng is suggested to contribute to a protective effect in neurodegenerative disorders. The aim of the present study was to evaluate the possible protective effect of ginseng against the midbrain injury induced by acrylamide in adult male albino rats. A total of 35 adult male albino rats were used. They were divided into three groups. Group I [15 animals] was allowed water ad libitum and fed a standard diet [control]. Group II [10 animals] was given acrylamide orally by means of a gastric tube daily at a dose of 30 mg/kg for 4 weeks. Group III [10 animals] was given acrylamide daily at the same dissolution, dose, route and duration as group II concomitantly with ginseng solution through a gastric tube at a dose of 20 mg/kg. Samples from the brainstem were taken and processed for light and electron microscopic investigation. Light microscopic examination of the midbrain of the acrylamide-treated animals showed signs of injury. Glial fibrillary acidic protein-positive cells were more abundant in the midbrain of treated animals compared with control animals. Ultrastructural study of the midbrain of the acrylamide-treated group showed dilated RER in association with mitochondria with destroyed cristae. Many myelinated nerve fibers showed degenerative changes. These structural changes were much less pronounced in animals concomitantly treated with acrylamide and ginseng. Ginseng can reduce the severity of the injurious effects induced by acrylamide

Immunotoxicity of acrylamide in female BALB/c mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the immunotoxicity of acrylamide (ACR) in female BALB/c mice.</p><p><b>METHODS</b>A total of 200 female mice weighing 18-22 g were randomly divided into four clusters based on body weight, and each weight-based cluster included five groups (10 mice per group): negative control, positive control (cyclophosphamide), low, intermediate, and high dose ACR groups, and all the groups were administered ACR by gavage for 30 days. At the end of the study, the immunotoxicological effects of the ACR were evaluated through immunopathology, humoral immunity, cellular immunity, and non-specific immunity.</p><p><b>RESULTS</b>The terminal body weight, spleen and thymus weights, lymphocyte counts in the ACR-H group were decreased, pathological changes were observed in lymph glands, thymus and spleen. %T cells in blood lymphocytes were significantly increased in all ACR-treated groups, and a significant reduction of % natural killer(NK) cells and increase of %Th cells were observed in the ACR-H group. interleukin-6(IL-6), Concanavalin A(ConA)-induced splenocyte proliferation and serum half hemolysis value (HC50) were also significantly suppressed in the ACR-H group.</p><p><b>CONCLUSION</b>ACR elicited an inhibitory effect on cellular and humoral immunity of mice after 30 day feeding.</p>

Pilot screening of acrylamide level in some Egyptian brands of potato aaaand corn products

Acrylamide is a chemical compound produced in starchy foods that have been cooked at high temperatures. Acrylamide is proven to be carcinogenic in rodents and a probable human carcinogen, with increasing evidence of positive associations with human cancers. Acrylamide is formed in potato crisps, chips, bread and crisp bread. lt was first discovered by scientists in Sweden in 2002. To determine the level of acrylamide in popular Egyptian brands of potato crisps and corn products produced by domestic food industrial factories. Seven brands of potato and eight brands of corn products were collected, crashed and after preparing the extracts of each sample, high performance liquid chromatography [HPLC] was used for measuring the amount of acrylamide. The amounts of acrylamide ranged 247-1677 micro g/kg in potato brands and <35-419 micro g/kg in corn products. As acrylamide is a dangerous toxin for human health, its level in these products, that are used extensively by people especially children, should be strictly traced and reduced