Morphological investigation of protective effects of CDP-choline on damage of the liver and small intestine in the experimental model of sepsis in rats induced by cecal ligation and puncture

Objective: Sepsis has a very high mortality rate among the intensive care unit patients and its incidence may rise up to 37%. CDP-choline which has mononucleotide structure, is an endogenous borderline product during the phosphatidylcholine synthezis from cellular membrane phospholipides. In literature, there are some researches manifesting the positive effects of exogenous CDP-choline on cellular membrane fonctions. Thus, in the study, we aim to examine the cytological and molecular mechanism of CDP-choline's effect on morphological damages of intestine and liver tissue due to intraperitoneal sepsis. Material and Method: During the experiments, 50 male Wistar albino rats were used. They divided into 5 groups. Group 1: sham group; Group 2: kontrol group; Group 3: 100 mg/kg CDP-choline group and Group 4: 200 mg/kg CDP-choline group and Group 5: sepsis group. Sepsis model was conducted by cecal ligation and puncture method. Vital parameters of animal subjects – such as pulse, mean arterial pressure and rectal heat – were documented. Also, qualitative and quantitative investigation of scale of cytologic damage of hepatic and intestinal tissue were performed. Results: Data analysis revealed that there was a significant difference between the initial pulse per minute and pulses per minute in the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (group 5) (p <0.05). In addition, there was a significant difference between the initial mean arterial pressure and the mean arterial pressure at the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (p <0.001). The mean arterial pressure values at the eighth hour were also different between the sham group and the CDP-choline group (p = 0.008 and p = 0.028). In the fourth hour, there was a difference between the sham group and the sepsis group, the control group and the sepsis group and the 200 mg CDP-choline group and the sepsis group (p = 0.002, p <0.001, p = 0.004, respectively). In terms of percentage change in the eighth hour, there were differences between 100 mg CDP-choline group with sham group, sepsis group with sham group, 100 mg CDP-choline group with control group and sepsis group with control group (p = 0.007, p <0.001, p = 0.048 and p <0.001). When the liver damage was evaluated in tissue samples, a statistically significant difference was found between whole groups (p <0.001). When CDP-choline groups were compared to each other, there was a significant difference between them (p <0.001). When the intestinal damage was evaluated, a statistically significant difference was found between the groups (p <0.001). When CDP-choline group was compared with group 5, there was a significant difference between the groups in terms of parameters (p <0.001). There was no statistically significant difference between CDP-choline dose groups in terms of small bowel damage parameters (p> 0.999). In the sepsis group, cellular death was observed in the tissue samples, but the cell death was not found in the tissues taken from group 4, where the dose of CDP-choline was higher. Conclusion: In the experimental sepsis model, CDP-choline treatment partially corrected the clinical parameters of sepsis and septic shock, and reversed microanatomic damage due to sepsis in hepatocytes and enterocytes, and citicoline given on certain doses inhibited endotoxemia-induced cell death.