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The present study was designed to look at the hematological disorders in gentamicin nephrotoxicity model, as kidney is considered as one of the hemopoietic organs. In a previous study, novel and classical kidney injury biomarkers were utilized to evaluate the nephroprotective potential of Carica papaya leaf extract (CPLE) in the same model in albino rats. Gentamicin (100 mg/kg, subcutaneously, for 21 consecutive days) resulted in significant decreases in red blood cell (RBC) count, hemoglobin concentration (HGB), and packed cell volume (PCV) value, with minimal alterations in erythrocytic indices. Leucogram showed leukocytosis, granulocytosis, and thrombocytopenia. Erythropoietin (EPO) levels were also drastically decreased by the end of the experimental course. Serum iron, unsaturated iron-binding capacity (UIBC), total iron binding capacity (TIBC), transferrin saturation %, and serum transferrin concentration values were significantly decreased in contrast to ferritin, which was increased. When concurrently administered with gentamicin, CPLE (150 and 300 mg/kg, orally via gastric tube, for 21 days) significantly protected against the drastic effects of the former on the blood profile with improving potentials on erythrogram, leukogram, thrombocytes, EPO, iron and its indices, in a dose-dependent manner. These data may suggest CPLE as an appreciated blood homeostatic and nephroprotective agent from a natural source that could be a good remedy in conditions associated with blood disorders.

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OBJECTIVE: This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity. METHODS: Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 µL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed. RESULTS: CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model. CONCLUSION: These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.

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The present study is aimed at utilization of novel and classical kidney function biomarkers to evaluate the nephroprotective potential of Carica papaya leaf extract (CPLE) in gentamicin nephrotoxicity model in albino rats. The used classical biomarkers were urea and creatinine; while the new biomarkers were Kidney injury molecule-1 (KIM-1) and Clusterin. Forty-five male albino rats were assigned into five groups and subjected to different treatments for nine consecutive days (vehicles; gentamicin, 100 mg/kg, subcutaneously; ascorbic acid, 200 mg/kg, orally; CPLE, 150 and 300 mg/kg b wt., orally). Three rats/group were killed on days 3, 6, and 9 for blood and tissue samples for renal and oxidation markers. Gentamicin resulted in significant increase in urea and creatinine only by the end of the experimental course; while the novel biomarkers were evident as early as 3 days upon gentamicin injection. When concurrently administered with gentamicin, CPLE significantly protected kidney tissues against gentamicin nephrotoxic effects indicated by decrement of both the novel and the classical standard biomarkers, in a dose-dependent manner. CPLE-mediated protection was attributed to its antioxidant potential indicated by significant inhibition of malondialdehyde (MDA) levels in both serum and kidney homogenates. The results were further supported by histopathological examination that revealed considerable amelioration of the pathological microscopic alterations induced by repeated gentamicin injection. Phytochemical analysis of CPLE indicated presence of tannins and flavonoids. These data may suggest CPLE, based on improvement of both classical and novel renal markers, as a highly potent nephroprotective and antioxidant from natural source that could be a good remedy in conditions associated with renal disorders.

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Punica granatum flower and leaf were extracted with hydromethanol 50% and evaluated for antioxidant activity using phosophomolybdenum, DPPH, reducing power, and -OH-scavenging assays; and for antiinflammatory activity using HRBC-MS assay. Both extracts exhibited antioxidant activities indicated by DPPH decolorization and -OH-scavenging and increased Ferric reducing and phosphomolybdenum assays. Also, both extracts showed anti-inflammatory activities indicated by red blood cell membrane stabilization and reduced haemolysis-resultant haemoglobin. All results were concentration-dependent; and the leaf extract was more potent than that of the flower. The IC50 values for the flower and leaf extracts were 777.6 ± 1.48 & 656.4 ± 1.79; 184.3 ± 1.803 & 113.9 ± 2.001; 130.8 ± 1.66 & 81.4 ± 2.1; 132.4 ± 1.55 & 79.67 ± 0.03; and 126.1 ± 1.35 & 67.25 ± 1.28 µg/mL in phosophomolybdenum, DPPH, reducing power, -OH-scavenging and red blood cell-membrane stability assays, respectively. Phytochemical analysis revealed presence of tannins and flavonoids with results more obvious in the leaf extract. These active principle contents may account for the recorded antioxidant and anti-inflammatory activities of both extracts. These findings provide evidence for the possible beneficial applications of the Punica granatum leaf and flower extracts in stress-related disease conditions and for maintenance of normal health status and well-being as well.

A flor e a folha de Punica granatum foram extraídas com hidrometanol 50% e avaliadas quanto à atividade antioxidante usando ensaios de fosfomolibdênio, DPPH, poder redutor e de eliminação de OH; E para atividade anti-inflamatória utilizando ensaio de HRBC-MS. Ambos os extratos exibiram actividades antioxidantes indicadas por descoloração do DPPH e por eliminação de OH e aumento nos ensaios de redução férrica e fosfomolibdênio. Além disso, ambos os extratos mostraram atividades anti-inflamatórias indicadas pela estabilização da membrana dos glóbulos vermelhos e redução da hemoglobina resultante da hemólise. Todos os resultados foram dependentes da concentração; E o extrato foliar era mais potente que o da flor. Os valores de IC50 para os extractos de flores e folhas foram de 777,6 ± 1,48 & 656,4 ± 1,79; 184,3 ± 1,803 e 113,9 ± 2,001; 130,8 ± 1,66 & 81,4 ± 2,1; 132,4 ± 1,55 & 79,67 ± 0,03; E 126,1 ± 1,35 & 67,25 ± 1,28 µg / mL em ensaios de fosfomolibdênio, DPPH, poder redutor, eliminação de OH e de estabilidade de membrana de glóbulos vermelhos, respectivamente. A análise fitoquímica revelou presença de taninos e flavonóides com resultados mais evidentes no extrato foliar. Estes conteúdos de princípio activo podem explicar as actividades antioxidantes e anti-inflamatórias registadas de ambos os extractos. Estes resultados fornecem evidências para as possíveis aplicações benéficas da folha de Punica granatum e extratos de flores em condições de doença relacionadas ao estresse e para a manutenção do estado de saúde normal e bem-estar também.

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