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The aim of this study was to prepare Eudragit Retard L (Eudragit RL) nanoparticles (ENPs) and to determine their properties, their uptake by the human THP-1 cell line in vitro and their effect on the hematological parameters and erythrocyte damage in rats. ENPs showed an average size of 329.0 ± 18.5 nm, a positive zeta potential value of +57.5 ± 5.47 mV and nearly spherical shape with a smooth surface. THP-1 cell lines could phagocyte ENPs after 2 h of incubation. In the in vivo study, male Sprague-Dawley rats were exposed orally or intraperitoneally (IP) with a single dose of ENP (50 mg/kg body weight). Blood samples were collected after 4 h, 48 h, one week and three weeks for hematological and erythrocytes analysis. ENPs induced significant hematological disturbances in platelets, red blood cell (RBC) total and differential counts of white blood cells (WBCs) after 4 h, 48 h and one week. ENP increased met-Hb and Co-Hb derivatives and decreased met-Hb reductase activity. These parameters were comparable to the control after three weeks when administrated orally. It could be concluded that the route of administration has a major effect on the induction of hematological disturbances and should be considered when ENPs are applied for drug delivery systems.

International audience; The aim of this study was to prepare Eudragit Retard L (Eudragit RL) nanoparticles (ENPs) and to determine their properties, their uptake by the human THP-1 cell line in vitro and their effect on the hematological parameters and erythrocyte damage in rats. ENPs showed an average size of 329.0 +/- 18.5 nm, a positive zeta potential value of +57.5 +/- 5.47 mV and nearly spherical shape with a smooth surface. THP-1 cell lines could phagocyte ENPs after 2 h of incubation. In the in vivo study, male Sprague-Dawley rats were exposed orally or intraperitoneally (IP) with a single dose of ENP (50 mg/kg body weight). Blood samples were collected after 4 h, 48 h, one week and three weeks for hematological and erythrocytes analysis. ENPs induced significant hematological disturbances in platelets, red blood cell (RBC) total and differential counts of white blood cells (WBCs) after 4 h, 48 h and one week. ENP increased met-Hb and Co-Hb derivatives and decreased met-Hb reductase activity. These parameters were comparable to the control after three weeks when administrated orally. It could be concluded that the route of administration has a major effect on the induction of hematological disturbances and should be considered when ENPs are applied for drug delivery systems.

This study aimed to determine the total phenols and DPPH scavenging properties of aqueous (AE) and ethanolic (EE) extracts of papaya fruits in vitro and to evaluate their hepatoprotective effects against aflatoxicosis in vivo. Sixty female Sprague-Dawley rats were divided into six groups and treated for 4 weeks including the control group, the group fed aflatoxins-contaminated diet (2 mg/ kg diet); the group treated orally with EE (250 mg/kg b.w); the group treated orally with AE (250 mg/ kg b.w); the groups fed AFs-contaminated diet and treated with EE or AE. At the end of the treatment period, blood and liver samples were collected for biochemical, histological and histochemical study. The results revealed that AE has higher total phenol content and DPPH scavenging activity if compared to EE. The in vivo results indicated that animals fed AFs-contaminated diet showed significant biochemical, histological and histochemical changes typical to those reported in the literature. Animals treated with the extracts and AFs showed a significant improvement in all biochemical parameters, histological and histochemical picture of the liver. This improvement was more pronounced in the group treated with AE. It could be concluded that papaya fruits can be used as a functional dietary ingredient to reduce hepatotoxicity., This study aimed to determine the total phenols and DPPH scavenging properties of aqueous (AE) and ethanolic (EE) extracts of papaya fruits in vitro and to evaluate their hepatoprotective effects against aflatoxicosis in vivo. Sixty female Sprague-Dawley rats were divided into six groups and treated for 4 weeks including the control group, the group fed aflatoxins-contaminated diet (2 mg/ kg diet); the group treated orally with EE (250 mg/kg b.w); the group treated orally with AE (250 mg/ kg b.w); the groups fed AFs-contaminated diet and treated with EE or AE. At the end of the treatment period, blood and liver samples were collected for biochemical, histological and histochemical study. The results revealed that AE has higher total phenol content and DPPH scavenging activity if compared to EE. The in vivo results indicated that animals fed AFs-contaminated diet showed significant biochemical, histological and histochemical changes typical to those reported in the literature. Animals treated with the extracts and AFs showed a significant improvement in all biochemical parameters, histological and histochemical picture of the liver. This improvement was more pronounced in the group treated with AE. It could be concluded that papaya fruits can be used as a functional dietary ingredient to reduce hepatotoxicity. Avaliação das propriedades radicais de limpeza e o papel protetor deextratos de frutos de mamão contra o estresse oxidativo em ratosalimentados com dieta contaminada com aflatoxinas.ResumoEste estudo teve como objetivo determinar o teor de fenóis e propriedades de remoção deDPPH em extratos aquosos (AE) e etanólicos (EE) de frutos de mamão in vitro e avaliar seus efeitoshepatoprotetores contra aflatoxicose in vivo. Sessenta fêmeas Sprague-Dawley foram divididas emseis grupos e foram tratadas durante 4 semanas, sendo o grupo de controle, o grupo alimentadocom a dieta contaminada com aflatoxinas-(2 mg / kg de dieta), o grupo tratado oralmente comEE (250 mg / kg de peso corporal); o grupo tratado por via oral com AE (250 mg / kg de pesocorporal), os grupos alimentados com dieta AFS contaminado e tratado com EE ou AE. No finaldo período de tratamento, as amostras de sangue e do fígado foram colhidas para estudosbioquímicos, histológicos e histoquímicos. Os resultados revelaram que AE tem maior teor defenóis totais e atividade DPPH se comparado a EE. Os resultados in vivo indicaram que os animaisalimentados com a dieta AFs contaminado mostraram significativas alterações bioquímicas,histológicas e histoquímicas, típicas dos relatos na literatura. Os animais tratados com os extratose AFS apresentaram uma melhora significativa em todos os parâmetros bioquímicos, quadrohistológico e histoquímico do fígado. Esta melhoria foi mais pronunciada no grupo tratado com AE.Pode-se concluir que os frutos de mamoeiro podem ser usados como um ingrediente funcional nadieta para reduzir a hepatoxicidade.

The current study was undertaken to evaluate the hepatoprotective potential of aged garlicextract (AGE) against hepatotoxicity induced by CCl4 in adult male rats. CCl4 intoxication (1ml/kg b.w., twice a week, i.p. for 4 weeks) significantly increased oxidative stress as indicated byincreased hepatic MDA formation, decreased both serum total and reduced glutathione contents,and inhibition of hepatic glutathione reductase and serum paraoxonase 1(POX1) activities. Inaddition, treatment with CCl4 produced a significant increase in the activities of serum ALT, ASTand albumin level with a significant decrease in total protein level. Moreover, treatment with CCl4resulted in significant increase in the levels of total cholesterol, LDL-cholesterol, triglycerides as wellas creatine kinase isoenzyme and lactate dehydrogenase activities, and a significant decrease inHDL-cholesterol compared to control group. Oral treatment with AGE at doses of 100 and 200 mg/kg/day in combination with CCl4 significantly ameliorated the severity of CCl4- induced changes inthe above mentioned parameters in a dose- dependent manner. In conclusion, the present studyindicated that AGE improves POX1 activity and attenuates liver and cardiac dysfunction inducedby CCl4. The protective effects of AGE against CCl4 toxicity may be attributed to its antioxidant andfree radical scavenging activities due to its higher contents of organosulphur compounds., O presente estudo foi realizado para avaliar o potencial hepatoprotetor do extrato de alhoenvelhecido (AGE) contra hepatotoxicidade induzida por CCl4 em ratos machos adultos. CCl4intoxicação (1ml/Kg no peso corporal, duas vezes por semana, ip durante 4 semanas) aumentousignificativamente o Estresse oxidativo, tal como indicado pelo aumento da formação de MDAhepática, diminuição tanto de soro total e conteúdo de glutationa, e inibição da atividade deglutationa redutase hepática e paraoxonase soro 1 (POX1 ). Além disso, o tratamento com CCl4produziu um aumento significativo nas atividades séricas de ALT, AST e nível de albumina comuma diminuição significativa no nível de proteína total. Ademais, o tratamento com CCl4 resultounum aumento significativo dos níveis de colesterol total, colesterol-LDL, triglicerídeos, bem comoisoenzima creatina quinase e atividades da lactato desidrogenase, e uma diminuição significativanos níveis de HDL-colesterol, se comparado com o grupo controle. O tratamento oral com AGE emdoses de 100 e 200 mg / kg / dia em combinação com CCl4 demonstrou melhoras significativas nagravidade das alterações de CCl4 induzidas nos parâmetros acima mencionados, de uma maneiradose-dependente. Em conclusão, o presente estudo indicou que a idade aumenta a atividadede POX1 e atenua a disfunção no fígado e no coração induzidas por CCl4. Os efeitos protetoresde idade contra a CCl4 toxicidade podem ser atribuídos aos seus antioxidantes e radicais livres,devido aos elevados teores de compostos organosulfurados.

The present study was conducted to study the chemoprotective effect of Egyptian rosemary extract (RE) against CCl4-induced hepatotoxicity. Eight experimental groups were used as follow: (1) control; (2&3) RE alone (440 mg/kgb.w) for 4 and 8 weeks, respectively; (4) CCl4 (1ml/kg b.w, twice a week, i.p) for 4 weeks; (5&7) RE (220&440 mg/kg) for 4 weeks before CCl4 for a similar period; and (6&8) RE (220&440 mg/kg) for four weeks before CCl4 in combination with RE another four weeks. The sequential CCl4 treatment induced significant changes in serum biochemical parameters accompanied by sever histological and histochemical changes of the liver tissue, while administration of 440 mg/kg/day for either 4 or 8 weeks did not induce any changes. Administration of RE before or during the treatment with CCl4 improved all biochemical parameters and histological picture of the liver, in a dose and duration-dependant manner. It could be concluded that RE has a protective effects against hepatotoxicity., The present study was conducted to study the chemoprotective effect of Egyptian rosemary extract (RE) against CCl4-induced hepatotoxicity. Eight experimental groups were used as follow: (1) control; (2&3) RE alone (440 mg/kgb.w) for 4 and 8 weeks, respectively; (4) CCl4 (1ml/kg b.w, twice a week, i.p) for 4 weeks; (5&7) RE (220&440 mg/kg) for 4 weeks before CCl4 for a similar period; and (6&8) RE (220&440 mg/kg) for four weeks before CCl4 in combination with RE another four weeks. The sequential CCl4 treatment induced significant changes in serum biochemical parameters accompanied by sever histological and histochemical changes of the liver tissue, while administration of 440 mg/kg/day for either 4 or 8 weeks did not induce any changes. Administration of RE before or during the treatment with CCl4 improved all biochemical parameters and histological picture of the liver, in a dose and duration-dependant manner. It could be concluded that RE has a protective effects against hepatotoxicity. Efeito protetor de erva natural (Rosmarinus officinalis) contrahepatotoxicidade em ratos albinos machosResumoO presente estudo foi realizado para verificar o efeito quimioprotetor do extrato de alecrim egípcio(RE) contra toxidade hepática induzida por CCl4-. Oito grupos experimentais foram utilizados, comosegue: (1) controle; (2&3) apenas RE (440 mg/kgb.w) por 4 e 8 semanas, respectivamente; (4) CCl4(1ml/kg b.w, duas vezes por semana, i.p) durante 4 semanas; (5&7) RE (220&440 mg/kg) por quatrosemanas antes de CCl4 por um período similar; e(6&8) RE (220&440 mg/kg) por quatro semanasantes de CCl4 combinado com RE por outras quatro semanas. O tratamento seqüencial de CCl4induziu mudanças significativas nos parâmetros bioquímicos do soro, acompanhadas por severasmudanças histológicas e histoquímicas no tecido do fígado, enquanto que a administração de 440mg/kg/dia durante 4 ou 8 semanas não induziu nenhuma mudança. A administração de RE antesou durante o tratamento com CCl4 aumentou os parâmetros bioquímicos e histológicos do fígado,dependendo da dose e de sua duração. Pode-se concluir que RE apresenta efeito de proteçãocontra a toxidade hepática.