THE EFFECT OF RETINOL ON THE DEVELOPMENT OF THIOACETAMIDE-INDUCED FIBROSIS IN RATS

I. A. Kondratovich, V. Andreev, R. Kravchuk, I. E. Gulyai, S. Shalesnaya, V. Tsyrkunov
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Abstract

Perisinusoidal lipocytes, which store retinol and its derivatives in their lipid droplets, play a leading role in the development of liver fibrosis (LF). Objectives. To assess the effect of retinol on the development of thioacetamide (TAA) -induced LF in rats. Material and methods. The experiment was conducted on 48 male rats, represented by 6 groups. A 10 ml/kg TAA solution (2%) was administered intraperitoneally every other day. A retinol oil solution (800 IU/kg) in sunflower oil was given once a day. Two control groups received saline solution (1) and sunflower oil (2). Light and electron microscopy of the obtained semi- and ultrathin sections of the liver tissue was performed, the relative content of the connective tissue in the liver preparations was morphometrically evaluated, the content of retinol in blood plasma and the liver was determined. Results. Morphological studies of the control animals liver revealed the presence of a typical beam structure. 4 weeks after daily administration of retinol, the beam structure of the liver persisted, but lymphohistiocytic infiltration of portal tracts and disseminated intralobular infiltration were noted; there were inflammatory foci with a large number of cellular elements; the amount of the connective tissue significantly increased. After 4 weeks of TAA administration, a pronounced inflammatory reaction was observed in the central vein region, with the penetration into the lobe, the degree of fibrosis increased with the formation of thin incomplete septs. 4-week administration of retinol after 4-week TAA exposure led to increased fibrotic processes in the liver compared to animals treated with TAA alone. 8-week administration of TAA with 4-week administration of retinol resulted in 14-fold increase in the degree of fibrosis compared to control animals. Conclusions. The application of retinol in the used experimental dose stimulates the fibrosis process in rats’ liver.
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视黄醇对硫代乙酰胺致大鼠纤维化的影响
肝窦周围脂肪细胞在其脂滴中储存视黄醇及其衍生物,在肝纤维化(LF)的发展中起主导作用。目标。探讨视黄醇对大鼠硫代乙酰胺(TAA)诱导的LF发展的影响。材料和方法。实验选用雄性大鼠48只,分为6组。每隔一天腹腔注射10 ml/kg TAA溶液(2%)。视黄醇油溶液(800 IU/kg)含葵花籽油,每日1次。两组对照组分别给予生理盐水溶液(1)和葵花籽油(2)。对获得的肝组织半薄切片和超薄切片进行光镜和电镜观察,用形态计量学方法评价肝制剂中结缔组织的相对含量,测定血浆和肝脏中视黄醇的含量。结果。对照动物肝脏的形态学研究显示存在典型的梁结构。每日给予视黄醇4周后,肝脏梁状结构维持不变,但出现门静脉淋巴组织细胞浸润和弥散性小叶内浸润;炎性灶内有大量细胞因子;结缔组织的数量显著增加。TAA给药4周后,中央静脉区出现明显的炎症反应,随着向肺叶的渗透,纤维化程度增加,形成薄的不完全隔。与单独接受TAA治疗的动物相比,暴露于TAA 4周后给予视黄醇4周导致肝脏纤维化过程增加。与对照动物相比,8周服用TAA和4周服用视黄醇导致纤维化程度增加14倍。结论。视黄醇在实验剂量下的应用刺激了大鼠肝脏纤维化过程。
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