Abstract
Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of antioxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries. KEY WORDS: Hepatic steatosis; Mitochondrial dysfunction; NAFLD; Crataegus aronia; Simvastatin. Las complicaciones de la acumulacion de grasa en el higado, la esteatosis hepatica como la cirrosis hepatica y la insuficiencia hepatica se encuentran entre los problemas comunes de salud publica. Se intento investigar el dano a la ultraestructura de los hepatocitos inducido por la dieta alta en grasas (DAG) y se compararon los efectos terapeuticos a nivel celular de dos antioxidantes y agentes hipolipemiantes; Extracto de Crataegus aronia y simvastatina sobre esteatosis hepatica. Las ratas fueron alimentadas con DAG (grupo modelo) o dieta baja en grasa (DBG) (grupo control) durante 15 semanas antes de sacrificarse y los grupos terapeuticos comenzaron el tratamiento con estos agentes despues de la semana 11 hasta el dia del sacrificio. Se examinaron los tejidos hepaticos usando microscopia electronica de transmision (MET) y se analizaron homogeneizados de higado para marcadores de estres anti-oxidativo, que se sabe estan modulados en la lesion hepatica. Los examenes MET del grupo DAG mostraron un grave dano de los hepatocitos en comparacion con el grupo control, demostrado por esteatosis, dano mitocondrial y citoplasma vacio, reticulo endoplasmico rugoso y liso y membrana nuclear, el espacio intercelular dilatado entre hepatocitos y alteraciones en los lisosomas. Ademas, DAG mejoro el anti-oxidante glutation (GSH) y aumento el estres oxidativo TBARS biomarcadores. Tanto Crataegus aronia como simvastatina redujeron significativamente los lipidos y TBARS, trataron el dano a las celulas hepaticas, pero las estructuras de hepatocitos respondieron diferencialmente a estos agentes. Sin embargo, solo Crataegus aronia indujo GSH (p = 0,001). Concluimos que la esteatosis hepatica inducida por HFD causo un dano sustancial a la ultraestructura del hepatocito y los tratamientos de Crataegus aronia y simvastatina diferenciaron las lesiones hepaticas.