In vivo investigation on the chronic hepatotoxicity induced by sertraline.

Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100 g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8 mg/kg) for 9 weeks. The animals were subjected to morphometric, hepatohistological, histochemical and quantitative real-time polymerase chain reaction analyses. Sertraline chronic exposure induced morphometric changes and provoked histological and histochemical alterations including: hepatocytes hydropic degeneration, necrosis, nuclear alteration, sinusoidal dilation, bile duct hyperplasia, inflammatory cells infiltration, portal vessel congestion, Kupffer cells hyperplasia, portal fibrosis and glycogen depletion. In addition, the gene expression of drug and arachidonic acid metabolizing enzymes were reduced significantly (p value <0.05). The most affected genes were cyp4a12, ephx2, cyp2d9 and cyp1a2, demonstrating 5 folds or more down-regulation. These findings suggest that chronic sertraline treatment induced toxic histological alterations in the hepatic tissues and reduced the gene expression of drug metabolizing enzymes. Patients on chronic sertraline treatment may be on risk of hepatotoxicity with reduced capacity to metabolize drugs and fatty acids.

Ameliorative effect of propolis against hepatorenal alterations induced by methotrexate: morphohistopathological study / Efecto protector del propóleo en las alteraciones hepatorrenales inducidas por el metotrexato: estudio morfohistopatológico

Methotrexate (MTX) is widely used in the treatment of some forms of cancer but having severe side effects. The present work aimed to investigate the protective role of propolis treatment against alterations induced by MTX on the hepatic and renal tissues. Rabbits were exposed to MTX (0.25 mg/kg), with or without propolis (50 mg/kg) while hepatic and renal biopsies were examined for histological and histochemical abnormalities. Methotrexate induced hydropic degeneration, pyknosis, sinusoidal dilatation and bile duct hyperplasia in the liver together with renal tubular degeneration, glomerular shrinkage and hyaline droplet precipitation. While propolis partially ameliorated some of the morphometric and biochemical alterations, none of the hepatic alterations induced by MTX was protected by propolis treatment. Nevertheless glomerular shrinkage and renal tubule degeneration were partially protected in animals received both MTX plus propolis. It is concluded that propolis treatment has little or no ameliorative effect in protecting the hepatic and renal tissues from MTX toxicity.

El metotrexato (MTX) es ampliamente utilizado en el tratamiento de algunas formas de cáncer, pero tiene efectos secundarios graves. El presente trabajo tuvo como objetivo investigar el papel protector del tratamiento con própoleo frente a las alteraciones inducidas por el MTX en los tejidos hepático y renal. Se expusieron conejos a MTX (0,25 mg / kg), en grupos con y sin propóleo (50 mg / kg), y se realizaron biopsias hepáticas y renales, que fueron examinadas buscando anomalías histológicas e histoquímicas. El metotrexato indujo la degeneración hidrópica, picnosis, dilatación sinusoidal e hiperplasia del conducto biliar en el hígado, junto con la degeneración tubular renal, la contracción glomerular y la precipitación hialina. Mientras que el propóleo parcialmente mejoró algunas de las alteraciones morfométricas y bioquímicas, ninguna de las alteraciones hepáticas inducidas por MTX fue protegido por el tratamiento con propóleo. Sin embargo, la contracción glomerular y la degeneración de los túbulos renales fueron parcialmente protegidos en animales que recibieron MTX más propóleo. Se concluye que el tratamiento con propóleo tiene poco o ningún efecto mejorador en la protección de los tejidos hepáticos y renales sometidos a la toxicidad de MTX.

Zinc oxide nanoparticles hepatotoxicity: Histological and histochemical study.

Zinc oxide nanoparticles (ZnO NPs) are widely used in industry and cosmetic products with promising investment in medical diagnosis and treatment. However, these particles may reveal a high potential risk for human health with no information about hepatotoxicity that might be associated with their exposure. The present work was carried out to investigate the histological and histochemical alterations induced in the hepatic tissues by naked 35nm ZnO NPs. Male Wistar albino rats were exposed to ZnO NPs at a daily dose of 2mg/kg for 21days. Liver biopsies from all rats under study were subjected to histopathological examinations. In comparison with the control rats, the following histological and histochemical alterations were demonstrated in the hepatic tissues of rats exposed to ZnO NPs: sinusoidal dilatation, Kupffer cells hyperplasia, lobular and portal triads inflammatory cells infiltration, necrosis, hydropic degeneration, hepatocytes apoptosis, anisokaryosis, karyolysis, nuclear membrane irregularity, glycogen content depletion and hemosidrosis. The findings of the present work might indicate that ZnO NPs have potential oxidative stress in the hepatic tissues that may affect the function of the liver. More work is needed to elucidate the toxicity and pathogenesis of zinc oxide nanoparticles on the vital organs.