Cirrhosis Induces Apoptosis in Renal Tissue Through Intracellular Oxidative Stress

Abstract

-Background -Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. ObjectiveWe aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods -Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results -In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation.There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusion -These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis. HEADINGS -Liver cirrhosis. Renal insufficiency. Oxidative stress. Flow cytometry. Reactive oxygen species.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study

“…AKI is characterized by tubular cell injury and death (necrosis, apoptosis), which trigger endothelial activation and inflammatory cell recruitment . In an animal model, it has been reported that cirrhosis itself induces apoptosis in renal tissue by increase in intracellular reactive oxygen species and DNA damage . Therefore, it is quite possible that repeated minor insults to the kidney in a patient with cirrhosis, along with a chronic state of ongoing inflammation, causes reduction in GFR, leading to development of CKD.…”

“…(16) In an animal model, it has been reported that cirrhosis itself induces apoptosis in renal tissue by increase in intracellular reactive oxygen species and DNA damage. (17) Therefore, it is quite possible that repeated minor insults to the kidney in a patient with cirrhosis, along with a chronic state of ongoing inflammation, causes reduction in GFR, leading to development of CKD. These changes could accelerate in patients who have recurrent AKI or AKI that is severe and prolonged.…”

Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation

“…In this model, the characteristic features of the disease are established at approximately 28 d[10]. Studies have demonstrated that the changes occurring in cirrhosis in human patients are similar to those found in experimental models, including jaundice, hepatomegaly, splenomegaly, abnormal gas exchange, and oxidative damage[11-15]. …”

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