Oxidative stress describes the state level of oxidative damage in a cell, tissue or organ, caused by reactive oxygen species. Alcohol induces oxidative stress in the liver resulting in an imbalance between oxidants and anti-oxidants. Increased reactive oxygen species (ROS) production and glutathione (GSH) depletion, lead to abnormal breakdown of fat molecules (i.e., lipid peroxidation). This complex process results in the formation of toxic compounds and may contribute to the pathogenesis of alcoholic liver injury.
A research article to be published on January 14, 2008 in the World Journal of Gastroenterology addresses this question. The study was designed to study patients with alcoholic cirrhosis and to measure the mediators of oxidative stress (as NO• and cGMP) and antioxidant defenses (as total glutathione and thiol¨Creduced glutathione GSHr) and to correlate the levels with parameters of clinical liver disease severity, including MELD.
The consequence of the elevated levels of nitric oxide (NO•) is its cellular toxicity. The direct toxicity of NO• increased on reaction with superoxide anions (O2?•) to form peroxinitrite (ONOO?). The mechanism of injury caused by peroxinitrite involves multiple factors, including lipid peroxidation.
A wide variety of oxidative molecules such as reactive oxygen species (ROS) and or/depleting agents can alter the glutathione redox state, which is normally maintained by the activity of glutathione (GSH).
GSH has multiple functions in disease prevention and detoxification of chemicals or drugs while its depletion is associated with increased risk of toxicity and disease.
A deficiency of hepatic GSH and increased toxic free radicals may contribute to the progression of liver disease. Thus, oxidative stress seems to contribute to the pathogenesis of alcoholic liver injury and progression of alcoholic liver disease related to liver cirrhosis.
This investigation shows patients with decompensated alcoholic cirrhosis have higher levels of NO• and cGMP than compensated patients and that there is a positive correlation between the clinical score of the disease (Child Classes and MELD) and the abnormalities observed. Our findings suggest NO• and cGMP may contribute to progressive liver disease in these patients and influence the hemodynamic abnormalities. The need for further investigations correlating the serum levels of NO•, cGMP or GSH seen in decompensated cirrhotic patients with clinical outcomes (survival, variceal bleeding, renal failure and septic complications) is emphasized by our findings in order to develop prognostic parameters and delineate new therapeutic strategies.
Clinical trials should be designed to evaluate the possible effect of potential therapies targeted to these events in patients with alcoholic cirrhosis, and monitored with the markers indicated in our study.
The only curative treatment for alcoholic cirrhosis is liver transplantation, but only 20% of patients undergo transplantation, partially because of their inability to maintain prolonged abstinence. Earlier diagnosis and better treatment of patients with alcoholic liver disease requires more understanding of its pathogenesis and natural history. Our study opens new perspectives in this area.
Reference: Siqueira C, de Moura MC, Pedro AJ, Rocha P. Elevated nitric oxide and 3', 5'cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis. World J Gastroenterol 2008 January 14;14(2):236-242
Correspondence to: Dr Cintia Siqueira, Center of Gastroenterology, Institute of Molecular Medicine, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National