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Perioperative reactive oxygen species in infants with biliary atresia: A retrospective observational study
Naoki Hashizume1, Yoshiaki Tanaka1,2, Kimio Asagiri1,3
1Department of Pediatric Surgery, Kurume University School of Medicine.
Insights
Biliary atresia (BA) infants show elevated oxidative stress markers, particularly urinary 8-iso prostaglandin F2α, which correlates with bilirubin levels. Oxidative DNA damage may persist post-surgery in BA patients.
Area of Science:
- Pediatrics
- Hepatology
- Biochemistry
Background:
- Biliary atresia (BA) is a severe infant cholestatic liver disease causing progressive hepatic failure.
- Oxidative stress, an imbalance of reactive oxygen species (ROS), is implicated in various diseases.
- Measuring perioperative ROS in BA patients can offer insights into disease mechanisms and treatment response.
Purpose of the Study:
- To quantify perioperative levels of ROS markers in infants with biliary atresia.
- To compare ROS levels in BA patients with a control group.
- To investigate the correlation between ROS markers, liver function tests, and histological liver cholestasis.
Main Methods:
- Assessed 15 BA patients and 4 healthy controls, measuring serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days post-operation.
- Compared ROS levels with serum liver function tests and liver histology.
- Utilized median and interquartile range for data presentation.
Main Results:
- Urinary 8-iso-PGF2α was significantly higher in preoperative BA patients compared to controls.
- Urinary 8-iso-PGF2α levels positively correlated with total and direct bilirubin.
- No significant changes in SOD, 8-iso-PGF2α, or 8-OHdG were observed 30 days post-operation in BA patients; 8-OHdG levels remained elevated.
Conclusions:
- Elevated urinary 8-iso-PGF2α in BA patients suggests significant oxidative stress linked to cholestasis and bilirubin levels.
- Factors like inflammation and malabsorption may influence antioxidant activity and ROS levels.
- Urinary 8-OHdG indicates persistent oxidative DNA damage post-surgery in BA patients, irrespective of cholestasis improvement.
Abstract:
Biliary atresia (BA) is a devastating cholestatic disorder of infants that presents during the first several months after birth due to an idiopathic obstruction to the bile flow. Without prompt diagnosis, Kasai portoenterostomy, and deliberate follow-ups, the resulting cholestasis leads to progressive hepatic failure. Oxidative stress is an abnormal phenomenon inside cells or tissues caused by a disturbance in the reactive oxygen species (ROS). We aimed to measure perioperative ROS in BA patients.Data are presented as median (25th, 75th percentiles). We evaluated 15 BA patients (age 55 [48, 69] days) and measured ROS; serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days later to compare values with serum liver function tests and histologic grades of liver cholestasis. For compared BA patients, 4 normal subjects as control group (age 55 [27, 75] days) measured ROS and serum liver function tests.In BA patients, the preoperative serum SOD was 6.1 IU/mL (4.7, 7.2), urinary 8-iso-PGF2α was 1969 pg/mg Cre (1697, 2374), and urinary 8-OHdG was 37.1 ng/mg Cre (33.1, 53.7). At the postoperative day 30, the serum SOD was 5.2 IU/mL (4.2, 6.7), urinary 8-iso-PGF2α was 1761 pg/mg Cre (1256, 3036), and urinary 8-OHdG was 42.1 ng/mg Cre (29.65, 72.64). In ROS, there were no significant differences between the 2 periods. In control group, urinary 8-iso-PGF2α was significantly lower than that in preoperative BA patient group. However, other ROS were not significant differences between control group and BA patient group. The concentration of urinary 8-iso-PGF2α was positively correlated with total bilirubin and direct bilirubin levels (preoperatively: r = 0.6921, P = .0042 and r = 0.6639, P = .007, postoperatively: r = 0.6036, P = .0172 and r = 0.6464, P = .0092, respectively). The preoperative ROS were not correlated with histologic grades of liver cholestasis. Various factors such as liver inflammation, lipid malabsorption, and tissue disorders due to jaundice might affect the antioxidant activity and elevated urinary 8-iso-PGF2α. However, at least until 30 days later, urinary 8-OHdG as oxidative DNA damage might persist after the operation whether the cholestasis improved or not.
