INTRODUCTION:

The liver is important organ of vertebrates and some other animals¹ .In the human it is situated in the upper right of the abdomen, below the diaphragm. The liver has a wide range of functions, including detoxification of various metabolites, protein synthesis, and the production of biochemical’s necessary for digestion². The liver is a gland and plays a major role in metabolism with many functions in the human body, including regulation of glycogen storage, breakdown of red blood cells, plasma protein synthesis, and hormone production. It is an accessory digestive gland and produces bile, an alkaline compound which aids in digestion via the emulsification of lipids. The gallbladder, a small pear like organ that located just under the liver, stores bile produced by the liver^3.

The liver highly specialized tissue consisting of mostly hepatocytes regulates a wide variety of biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions². Liver damage leads to an inflammatory response and to the activation and proliferation of mesenchymal cell populations within the liver which remodel the extracellular matrix as part of an orchestrated wound-healing response. Chronic damage results in a progressive accumulation of scarring proteins (fibrosis) that, with increasing severity, alters tissue structure and function, leading to cirrhosis and liver failure. Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases, including viral hepatitis B or C infection⁴. The fibroblasts are derived from sources within and out with the liver. Other fibroblasts emerge from the portal tracts within the liver. In addition, fibrogenic fibroblasts may also be generated through liver epithelial (hepatocyte and biliary epithelial cell)–mesenchymal transition. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs). Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation⁵. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, natural kill T cell NKcells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involve angiogenesis, Hepatic inflammation is the driving force behind liver fibrosis⁴. Many causes are responsible for liver fibrosis include alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), chronic hepatitis C, primary biliary cirrhosis⁷. Primary biliary cirrhosis (PBC) is considered an autoimmune disease, with immune damage of the interlobular bile ducts resulting in a regularly progressive ductopenia. PBC is generally a progressive disease leading to cirrhosis and death, although there have been reports of prolonged survival, with minimal progression of disease. Patients who are asymptomatic at appearance have a longer survival than those who are symptomatic. About one third of patients who are asymptomatic at appearance become symptomatic within 5 years. Symptomatic patients have an 8 year survival rate of approximately 50%. Survival models have been developed to predict outcome more precisely and are useful in determining the timing for liver transplantation. Patients with more difficult histological disease at diagnosis, however, have 30% and 50% rates of requiring liver transplantation or death over 10 and 20 years, respectively, despite treatment ⁶.

MATERIALS AND METHODS:

Experimental Animals:

Using 45 adult male rats (Rattus norvegicus) weighting 200-250 gm were obtained from the animals house in high institutes of fertility, University of Nahrain. The animals were housed in the animal house of Faculty of Science, University of Kufa, under standard environment condition (temperature 25-28 C° and 12 hr light-dark cycle) and allowed access to standard laboratory diet and water.

Experimental Protocol:

The rats were kept in animal house for acclimation to the laboratory condition for two weeks before they were used for the experiment. each group was formed 15 rats:

Group (1) rats were administrated of normal saline (as negative control).

Group (2) rats administered with CCl₄ for one month

Group (3) rats BDL for one week

Blood Collection:

At the end of experiments, each animal was anaesthetized by the mixture of xylazine 0.1 ml and ketamine 0.5 ml and they were scarified 15. Heart cut was finished with a 5 ml expendable syringe and 2-5 ml blood was drawn delicately and gradually. The blood was put in test tube containing gel and left for 30 minutes in room temperature and used to get serum through centrifugation at 3000 rpm for 15 minutes to separate serum and put in Epindroff tubes which kept at (- 20) in a cooler for assurance biochemical examination.

Measurement of Interleukin 17(IL17):

This laboratory test was determined by ELISA kit Bioassay Technology Laboratory (Catalog No: E015).

Determination of Serum Transaminase Activity:

Colorimetric determination of ALT and AST activity according to the Reitman and Frankel method ⁸, by using biomerieux kit.

Determination of Alkaline Phosphatase Activity:

Colorimetric determination of ALP according to Walters and Gerarde⁹ by using Linear chemicals kit.

Assessment of Total Cholesterol (TC):

Total cholesterol kit for quantitative determination of total cholesterol in human serum was supplied by Biolabo SA, France¹⁰.

Assessment of HDL- Cholesterol (HDL-C):

Serum HDL-Cholesterol level was measured by HDL-Cholesterol phosphotungstic acid (PTA) precipitant kit (Biolabo SA, France)¹¹.

Assessment of triglycerides (TG):

Triglycerides Kit was supplied by Biolabo SA, France. for measureable of triglycerides in human serum¹².

Assessment of very low Density Lipoprotein:

Very Low Density Lipoprotein (VLDL) was measured by the next principle: VLDL = TG (mg/dl) / 5 ¹¹.

Assessment of low Density Lipoprotein Level:

Low Density Lipoprotein (VLDL) were measured by the next formula:

LDL=TC(mg/dl)-VLDL(mg/dl)-DL(mg/dl).¹¹

Statistical Analysis:

The results were expressed as (Mean ± Standard Error) and Correlation coefficients were performed by using megastat.snd all comparison was performed by unpaired sample t-test, while the figures constructed using EXEL program. P-value < 0.05 was used as a level of statistically significant¹³.

RESULTS:

Effect of CCl4 and Bile Duct Ligation on level of IL17 in rats:

The result in figure (1) when compared male rat’s with control shows significant increase (p<0.05) in serum level of INT17 in both of CCl₄ for period one month and BDL for one week.