IMPROVEMENT OF THE MODELING AND DIAGNOSIS OF HEPATIC ENCEPHALOPATHY IN RATS

Manzhalii E. G., Kondratiuk V. E., Falalyeyeva T. M., Virchenko O. V., Golyshkin D. V.

METHODS AND METHODOLOGIES

Scentific article

One of the challenging problem in gastroenterology is the treatment of liver cirrhosis (LC) and hepatic encephalopathy (HE) as one of its dangerous complications. HE is the frequent disorder that hits approximately 50-80% of cirrhotic patients. This pathology is associated with progressive dystrophy of brain tissue and can lead to patients’ disability. Therefore, the study of the mechanisms of etiology and pathogenesis and possible strategies of treatment of HE is current issue of scientists all over the world. Today CCl4 is used for modeling of LC and HE in rats. However, this method has some limitations namely high mortality of lab animals or high duration of LC formation. Also diagnosis of HE was made on the study of the food conditioned reflex that allowed to evaluate only locomotor activity of animals but not their ability to think and remember. That is why the aim of the study was the optimization of HE modeling and diagnose. The modeling of HE in rats with hepatitis and liver cirrhosis was improved. Considering the literature data and selecting doses, intraperitoneally administration of 1 ml/kg 15% solution of CCl4 in olive oil four times a week for 4 weeks has been suggested for optimal simulation of HE in rats. The development of HE, namely the ability of animals to memorization, learning and thinking was studied by the formation of a food conditioned reflex in the T-shaped maze. 14 rats were divided into two groups: 1 — intact rats and 2 — rats pretreated with CCl4. The dynamic of reducing the time of getting animals to the food reinforcement in the maze as a result of remembering the location of food was estimated during 14 days. In the first day of food conditioned reflex study it was established that intact rats reached the food in 157 ± 47 sec. Contrary, the time of getting to food of CCl4-rats was 2,1 times (p<0.05) longer that suggests the less activity and lethargy of these animals. In the next 7 days, there were not any changes in the time of getting to food in T-shape maze in the intact group as well as in the group pretreated with CCl4. Since the 7th day we have shown a steady acceleration of finding the food by intact rats. However, there were not registered data about faster food reinforcement in the group of animals that got CCl4 injection. Moreover, in the group of intact rats we have established the decrease in time of finding the food by 92% (p<0.05) as compared with the first day of experiment. Such changes were not obvious for the CCl4-group: we did not find the significant difference between the reaching food of CCl4-rats at the start and at the 14th day of experiment in the T-shaped maze. Thus, we registered that the time of finding the food in the CCl4 group was 21.4 (p<0.001) greater than in the intact group at the 14th day of study in the T-shaped maze. The impairment of food conditioned reflex formation has showed lack of remembering and thinking in rats pretreated with CCl4. This confirms the progression of liver pathology and concomitant dystrophy of brain tissue with the development of HE. In conclusion, we have updated the scheme of modeling LC and HE by the decrease of time of the LC development and the reduction of animal mortality as result of toxic action by CCl4. The improved diagnosis of HE was achieved by using the methodology of forming a food conditioned reflex in rats. This method can be recommended as a basic for HE modeling and can be used for study new treatment strategies of this disease.

CCl4, liver cirrhosis, hepatic encephalopathy, food conditioned reflex

• 1. Grover V. P. The why and wherefore of hepatic encephalopathy / V. P. Grover, J. M. Tognarelli, N. Massie [et al.] // International journal of general medicine. — 2015. — Vol. 8. — P. 381-390.
• 2. Huang Y.-W. Pathogenesis and management of alcoholic liver cirrhosis: a review / Y.-W. Huang, S.-S. Yang, J.-H. Kao // Hepatic medicine : evidence and research. — 2011. — Vol. 3. — P. 1-11.
• 3. Liu A. Advances in cirrhosis: optimizing the management of hepatic encephalopathy / A. Liu, R. B. Perumpail, R. Kumari [et al.] // World journal of hepatology. — 2015. — Vol. 7, № 29. — P. 2871-2879.
• 4. Mendizabal M. Liver transplantation in acute liver failure: a challenging scenario / M. Mendizabal, M. O. Silva // World journal of gastroenterology. — 2016. — Vol. 22, № 4. — P. 1523-1531.
• 5. Nand N. Clinical profile of alcoholic liver disease in a tertiary care centre and its correlation with type, amount and duration of alcohol consumption / N. Nand, P. Malhotra, D. K. Dhoot // The Journal of the Association of Physicians of India. — 2015. — Vol. 63, № 6. — P. 14-20.
• 6. Rahimi R. S. Hepatic encephalopathy: how to test and treat / R. S. Rahimi, D. C. Rockey // Current opinion in gastroenterology. — 2014. — Vol. 30, № 3. — P. 265-271.
• 7. Wang J.-Y. Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in china / J.-Y. Wang, N.-P. Zhang, B.-R. Chi [et al.] // World journal of gastroenterology. — 2013. — Vol. 19, № 30. — P. 4984-4991.
• 8. Yang L. Effect of allogeneic umbilical cord mesenchymal stem cell transplantation in a rat model of hepatic cirrhosis / L. Yang, Y. Wang, X. Wang, Y. Liu // Journal of traditional Chinese medicine. — 2015. — Vol. 35, № 1. — P. 63-68.

«Bulletin of problems biology and medicine» Issue 1 part 1 (126), 2016 year, 239-243 pages, index UDK 616.36-004 + 615.917 + 612.821.5