TY - JOUR
T1 - Nitric Oxide and Redox Regulation in the Liver
T2 - Part I. General Considerations and Redox Biology in Hepatitis
AU - Diesen, Diana L.
AU - Kuo, Paul C.
PY - 2010/7
Y1 - 2010/7
N2 - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
AB - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
KW - antioxidants
KW - ethanol-induced hepatitis
KW - fibrosis
KW - hepatitis
KW - hepatocytes
KW - ischemia/reperfusion
KW - nitric oxide
KW - oxidative stress
KW - proteomics
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=77953293358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953293358&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2009.09.019
DO - 10.1016/j.jss.2009.09.019
M3 - Review article
C2 - 20444470
AN - SCOPUS:77953293358
SN - 0022-4804
VL - 162
SP - 95
EP - 109
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -