Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, Italy.
J Biol Regul Homeost Agents. 2011 Jan-Mar;25(1):47-56.
Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.
非酒精性脂肪性肝病，以肝细胞凋亡为特征，在脂肪肝和非酒精性脂肪性肝炎（更严重的形式）中是不同的。细胞凋亡是半胱天冬酶依赖性的，与线粒体膜去极化和细胞色素 c 释放有关。根据肝细胞暴露于游离脂肪酸会导致活性氧（ROS）产生增加和线粒体损伤，而抗氧化物质的存在会使其达到平衡的假说，研究了患有不同严重程度非酒精性脂肪性肝病患者的循环γ-谷氨酰转移酶、细胞色素 c、甘油三酯和未结合胆红素水平。186 名连续患者最近出现了超声检查表现为肝脏明亮而无任何已知来源的肝病，其中 89 名患者进行了肝活检。45 名患者根据组织学结果被分配到脂肪肝组，44 名患者形成非酒精性脂肪性肝炎组。选择了 27 名年轻、瘦、明显健康的个体作为对照组。γ-谷氨酰转移酶水平正常或略有升高，而所有非酒精性脂肪性肝病患者的未结合胆红素浓度均升高。将本研究结果与其他涉及凋亡特征疾病的相关研究结果进行比较，我们并未发现非酒精性脂肪性肝病患者循环细胞色素 c 水平升高。更重要的是，我们将患者分为单纯性脂肪肝或更严重的非酒精性脂肪性肝炎，发现他们的细胞色素 c 和γ-谷氨酰转移酶水平相似，p=0.19 和 0.11。非酒精性脂肪性肝病患者的血清甘油三酯水平高于健康组，p=0.001。这些发现可能反映了氧化应激和抗氧化反应之间的平衡，而不是细胞色素 c 作为线粒体损伤可靠生物标志物缺乏可靠性。
