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Abstract Hepatoprotective and therapeutic effect of propolis in CCl4 induced acute hepatotoxicity in rats were investigated. This study was carried out on 200 male albino rat, weighting 200 - 250 gm. Rats were housed in a separate metal cages under the same constant environmental and nutritional condition through the period of investigation. Rats injected intra peritoneal with CCl4 50 % dissolved in equal volume of olive oil at a dose of 3 ml/ kg b.w for one day in hepatoprotective group and for two successive days in therapeutic group. Propolis water extract (PE) was used at a dose of 200 mg/kg b.w administrated orally. Rats were randomly divided into two main groups as follows: Group A (Hepatoprotective group): Comprised 100 rats subdivided to 5 subgroups. 1- Control normal group (CN): received single dose of distilled water daily for 2 weeks orally , then injected intra peritoneal with normal saline 2- Control olive oil group (CO): received single dose of distilled water daily for 2 weeks orally, then injected intra peritoneal with olive oil. 3- Control propolis group (CP): received single dose of (PE) daily for 2 weeks, then injected intra peritoneal with normal saline. 4- Carbon tetrachloride group (CC): received single dose of distilled water daily for 2 weeks, then injected intra peritoneal with CCl4. 5- Propolis protected group (PP): received single dose of (PE) daily for 2 weeks, then injected intra peritoneal with CCl4. * Blood samples were collected after two weeks from protection by propolis and two and three days from induction of acute hepatotoxicity. * Tissue samples were collected two and three days after induction of acute hepatotoxicity. Group B ( Therapeutic group): Comprised of 100 rats subdivided to 5 subgroups. 1- Control normal group (CN): injected intra peritoneal with normal saline for two successive days then received single dose of distilled water daily for 4 weeks orally two days after intra peritoneal injection of normal saline. 2- Control olive oil group (CO): injected intra peritoneal with olive oil for two successive days then received single dose of distilled water daily for 4 weeks two days after intra peritoneal injection of olive oil. 3- Control propolis group (CP): injected intra peritoneal with normal saline for two successive days then received single dose of (PE) daily for 4 weeks via two days after intra peritoneal injection of normal saline. 4- Carbon tetrachloride group (CC): injected intra peritoneal with CCl4 for two successive days then received single dose of distilled water daily for 4 weeks two days after induction of acute hepatotoxicity. 5- Propolis treated group (PT): injected intra peritoneal with CCl4 for two successive days, then received single dose of (PE) daily for 4 weeks two days after induction of acute hepatotoxicity. * Blood samples were collected after 1, 2, 3 and 4 weeks from the onset of propolis treatment. * Tissue samples were collected two and three days after the onset of propolis treatment. Blood samples were used for detection of the following parameters: 1- ALT. 2- AST. 3- ALP. 4- Total protein. 5- Albumin. 6- Total bilirubin. 7- Urea. 8- Total cholesterol. 9- Triacylglycerol. 10- HDL-C. 11- LDL-C. 12- VLDL-C. 13- L-MDA. Liver tissue homogenates were used for detection of the following parameters: 1- NO. 2- GSH. 3- GST. 4- Catalase. The obtained results demonstrated that: 1- ALT: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant increase in ALT after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase observed two days after induction of acute hepatotoxicity when compared to CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in ALT allover the experimental period as compared with CN group. • However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1 and 2 weeks as compared with CN group. 2- AST: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant decrease in AST after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant increase observed two and three days after induction of acute hepatotoxicity when compared to CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant decrease in AST observed after 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited non significant increase after 1 and 2 weeks and non significant decrease after 3 and 4 weeks as compared with CN group. 3- ALP: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant increase in ALP after 1 week and non significant decrease after 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant decrease in ALP after 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1 and 2 weeks as compared with CN group. 4- Total protein: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant decrease in total protein after 1 week and non significant increase after 2 week as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant decrease two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in total protein allover the experimental period as compared with CN group. ● However CCl4 exhibited a significant decrease allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a non significant change allover the experimental period as compared with CN group. 5- Albumin: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant change in albumin after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant change two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in albumin allover the experimental period as compared with CN group. ● However CCl4 exhibited a significant decrease allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant decrease after 1 and 3 weeks as compared with CN group. 6- Total bilirubin: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant change in total bilirubin after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in total bilirubin allover the experimental period as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1, 2 and 3 weeks as compared with CN group. 7- Urea: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited significant increase in urea after 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase 2 days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in urea allover the experimental period as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1 week as compared with CN group. 8- Total Cholesterol: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a significant increase in total cholesterol after 1 , 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant increase in total cholesterol after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase allover the experimental period when compared to CN group. 9- Triacylglycerol: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant increase in triacylglycerol after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant increase in triacylglycerol after 1 and 2 weeks and significant decrease after 4 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1 week and significant decrease after 3 and 4 weeks as compared with CN group. 10-HDL-C: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant decrease in HDL-C after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant decrease in HDL-C after 3 and 4 weeks as compared with CN group. ● However CCl4 exhibited a significant decrease allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase allover the experimental period as compared with CN group. 11- LDL-C: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a significant increase in LDL-C after 1 and 2 weeks as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant increase in LDL-C after 1 week as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 2 weeks as compared with CN group. 12- VLDL-C: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a significant increase in VLDL-C after 1 week as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant increase in VLDL-C after 1 and 2 weeks and significant decrease after 4 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase after 1 week and significant decrease after 3 and 4 weeks as compared with CN group. 13- L-MDA: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a significant increase in L-MDA after 1 week as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant decrease two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a significant increase in L-MDA after 4 weeks as compared with CN group. ● However CCl4 exhibited a significant increase allover the experimental period as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase allover the experimental period as compared with CN group. 14- NO: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant change in NO after two and three days as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant decrease in NO after two and three days as compared with CN group. ● However CCl4 exhibited a significant increase after two and three days as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase two and three days after onset of propolis treatment as compared with CN group. 15- GSH: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant decrease in GSH after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant change two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant change in GSH after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant increase two and three days after onset of propolis treatment as compared with CN group. 16- GST: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant increase in GST after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant increase in GST after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a significant decrease after two days which became significant increase three days after onset of propolis treatment as compared with CN group. 17- Catalase: A- Hepatoprotective group: ● Administration of PE to normal rats exhibited a non significant decrease in catalase after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of CCl4 to propolis protected rats exhibited a non significant increase two and three days after induction of acute hepatotoxicity as compared with CN group. B- Therapeutic group: ● Administration of PE to normal rats exhibited a non significant decrease in catalase after two and three days as compared with CN group. ● However CCl4 exhibited a significant decrease after two and three days as compared with other groups. ● While administration of PE to rats with acute hepatotoxicity exhibited a non significant increase two and three days after onset of propolis treatment as compared with CN group. |