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.

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.

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.

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.

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

Turmeric may protect cells from oxidative stress by acrylamide in-vivo

Turmeric is a perennial herb; the rhizome is the portion of the plant that is used medicinally. It is the source of the spice turmeric with characteristic yellow color. Acrylamide is found in some foods that are cooked at high temperatures. It appears to be formed as a by product of the Maillard reaction. Maillard reaction is a type of non -enzymatic browning, which involves the reaction of simple sugars [carbonyl groups] and amino acids. Only the acrylamide monomer is toxic. Present work is focused on turmeric's antioxidant activity against acrylarnide toxicity. Rats were divided into three groups [7 rats/ group]. Group A served as negative control that was fed on standard diet [commercial diet] for 11 days. Group B was fed for 11 days on standard diet containing 0.34g acrylamide / kg diet as a positive control. Group C received standard diet with turmeric [0.5%] and same concentration 0.34g acrylamide/ kg diet for 11 days as a protective group. Results revealed that kidney, brain and lung tissues were disturbed when rats were fed on acrylamide diet. Turmeric had ameliorated the antioxidant status in these organs. It is concluded that turmeric as a natural antioxidant has protected from acrylamide toxicity

Genotoxicity and toxicological effects of acrylamide on reproductive system in male rats

The toxicity of acrylamide was evaluated through mutagenicity of Salmonella, chromosome aberration of Chinese hamster lung fibroblasts, micronucleus formation in mice and reproductive toxicity in rats. Based on Ames test, acrylamide showed mutagenic potency for strains TA98 and TA100. Moreover, both chromosomal aberration assay and micronucleus assay indicated that acrylamide might have genotoxic potency; the chromosomal aberration frequencies were observed to be proportional to acrylamide concentrations of 5-50 mM, and acrylamide significantly increased micronuclei in peripheral blood cells of mice at doses of higher than 72.5 mg/kg. Male rats were treated with acrylamide at doses of 0, 5, 15, 30, 45, or 60 mg/kg/day for 5 consecutive days, and the toxicity of acrylamide was observed. In the group treated with the highest dose of acrylamide (60 mg/kg/day), the loss of body weight and reduced testis weight were observed. Also the epididymides weights were reduced significantly in all the groups treated with acrylamide. The number of sperms in cauda epididymidis decreased significantly in an acrylamide dose-dependent manner. Rats treated with 60 mg/kg/day of acrylamide showed several histopathological lesions in the seminiferous tubules. There were thickening and multiple layering of the tubular endothelium, and the formation of many multinucleated giant cells in seminiferous tubules. Taken together, acrylamide not only causes the genotoxicity of eukaryotic cells and mice but also shows the toxicological effects on reproductive system in male rats.

Acrylamide in food: an overview

A hypothesis that acrylamide is formed by/upon cooking was confirmed in experimental animals by a verification of the identity of the acrylamide adduct in hemoglobin [Hb]. This was comprehensively approved by GC/MS analysis and the demonstration that the increased adduct levels were compatible with expectation from the contents of acrylamide determined in fried feeds. A significant dependence of acrylamide formation on temperature was demonstrated. Extensive efforts were made to assess the human exposure to acrylamide by monitoring several metabolites excreted in the urine as well as products resulting from biological alkylation by acrylamide. The results from in vivo studies conducted on rats explored that dermal absorption ranged from approximately 14 to 61% of the applied dose. Meanwhile, it was obvious that acrylamide was widely distributed in all tissues of the body. The major metabolite formed from acrylamide via the cytochrome P450 pathway was glycidamide. Conjugation to reduced glutathione [GSH] catalyzed by glutathione S-transferase [GST] and excretion as mercapturic acid is a major pathway for the metabolism of acrylamide. Experiments revealed neuro and reproductive toxicity of acrylamide. The International Agency of Research on Cancer [IARC] has classified acrylamide as probably carcinogenic to humans. Acrylamide in foods can be determined by GC/MS, HPLC and liquid chromatography-mass spectrometry [LC-MS] using the MS/MS mode. For the GC/MS and HPLC methods, the achieved detection level of acrylamide was 5 mug/kg; while, for LC-MS/MS method, it was 10 mug/kg. The latter method is simple and preferable for routine analysis