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Abstract The present study investigates some pharmacodynamic effects of Ricobendazole and Ivermectin each alone and their concomitant administration in mature male rats and lactating cows . I-Experiments on mature male rats : Mature male rats were divided into 4 groups each group of 15 rats. group 1:Rats were treated with Ricobendazole (7.50 mg / kg.b.wt.S/C.) group 2:Rats were treated with Ivermectin ( 0.56 mg / kg.b.wt. S/C). group 3: Rats were treated with Ricobendazole concomitantly with Ivermectin group 4: Rats were treated with propylene glycol at a dose of 2ml / kg.b.wt. S/C and kept as a control . Blood samples were collected from treated and control rats at the end of 2nd , 4th and 8th week from drug administration to examine the effect of these drugs on blood picture, hepatic and renal functions , testosterone level , semen characters , index weight of some body organs and the histological structure of the reproductive organs , liver , kidney and spleen. II-Experiments on lactating cows : Firstly, faecal examination was carried out to all cows present in the farm. Three groups of cows, each of 5 animals infested with flukes and / or worms were classified and labled with numbers according to the most dominant parasitic eggs found in the faecal matter as follows : 1- Group1: infested with fasciola and paramphistomum spp flukes and treated with Ricobendazole at a dose of 150 mg / 20kg. b.wt. S/C. 2- group 2 : infested with nematodes and paramphistomum spp. and treated with Ivermectin at a dose of 10 mg / 50 kg. b.wt. S/C. Summary 391 3- group 3 : infested with fasciola , nematodes and paramphistomum spp. and treated with Ricobendazole at a dose of 150 mg / 20 kg. b.wt. S/C concomitantly with Ivermectin at a dose of 10 mg / 50kg. b.wt. S/C. Faecal examination and blood samples from all treated groups were examined before treatment and at the end of 2nd , 4th and 8th week from drug administration . The anthelminitic efficacy (by recording egg shedding in feaces) , blood picture, and hepatic and renal function tests of lactating cows were recorded The obtained results are as follows : I- Findings on mature male rats : The effects of Ricobendazole (7.50 mg / kg.b.wt. S/C) or Ivermectin(0.56 mg / kg.b.wt. S/C) each alone and their concomitant administration on : A- Heamatological picture :- Hb concentration showed a significant decrease at 4th week from treatment in all treated groups . R.B.Cs count showed a significant increase at 8th week from treatment in all treated groups . PCV level in Ricobendazole and Ivermectin treated groups showed a significant decrease at 2nd week from treatment. Male rats treated with Ricobendazole concomitantly with Ivermectin showed non significant changes in PCV level at 2nd , 4th and 8th week from treatment. W.B.Cs count in male rats treated with Ricobendazole showed a significant increase at 2nd , 4th and 8th week from treatment . Male rats treated with Ivermectin and male rats treated with Ricobendazole concomitantly with Ivermectin showed a significant increase in W.B.Cs. count at 4th week from treatment. There was a significant increase in lymphocyte count at 8th week from treatment in all treated groups. Monocytes count showed a significant decrease at 2nd week from treatment in all treated groups. There was a significant increase in granulocyte count at 8th week from treatment in all treated groups as compared with the control group. Summary 391 B-Biochemical findings :- 1- Liver function tests : AST level showed a significant increase at 2nd week from treatment in all treated groups . ALT level in male rats treated with Ricobendazole and Ivermectin each alone showed a significant increase at 2nd week from treatment . Alkaline phosphatase level showed a significant increase in male rats treated with Ricobendazole and Ivermectin each alone at 4th week from treatment. Rats treated with Ricobendazole concomitantly with Ivermectin showed a significant increase in alkaline phosphatase level at 8th week from treatment. TSB level showed a significant increase at 4th and 8th week from treatment in all treated rats. LDH level showed a significant increase at 8th week from treatment in all treated rats. Total protein level showed a significant increase at 8th week from treatment in all treated groups .Albumin level showed a significant increase at 4th and 8th week from treatment in all treated groups . Globulin level showed a significant decrease at 2nd , 4th and 8th week from treatment in all treated groups. Cholesterol level showed a significant increase at 2nd week from from treatment in all treated groups as compared with the control group. 2-Kidney function tests : Urea levels were increased significantly at 4th week from treatment in all treated groups. Ricobendazole induced a significant increase in creatinine level at 4th week from treatment . A similar effect was induced by Ivermectin at 8th week from treatment. Ricobendazole concomitantly with Ivermectin induced insignificant changes in creatinine levels at 2nd,4th and 8th week from treatment as compared with the control group. C- Fertility findings:- Testosterone level showed a significant decrease at 8th week from treatment in all treated groups. Sperm count showed a significant decrease at 2nd , 4th and 8th week from treatment in all treated groups. Sperm motility showed non significant changes at 8th week from treatment in all treated groups. Sperm abnormalities showed a significant increase at 2nd , 4th and 8th week from treatment in all treated groups. Summary 391 Index weight of testis, epidedymis and accessory sex organs showed a significant decrease at 8th week from treatment in all treated groups as compared with the control group. D- Index weight of some internal organs:- Index weight of liver showed a significant increase at 2nd week from treatment in all treated groups. Index weight of kidney and spleen showed a significant decrease at 8th week from treatment in all treated groups as compared with the control group. E- Histopathological Findings:- Male rats treated by Ricobendazole and Ivermectin each alone and their concomitant administration showed many histological alterations such as some areas of necrosis in the liver, congestion and oedema in the kidney and lymphoid depletion of some white pulp in the spleen. Testes revealed congestion of the testicular blood vessels and interstitial edema, The epididymis showed interstitial edema and the seminal vesicles showed congested blood vessels and inflammatory exudate in glandular lumen . II- Clinical Findings on lactating cows : A-The anthelmintic Efficacy : Ricobendazole (150 mg / 20 kg.b.wt. S/C) showed its fasciolicidal activity against fasciola gigantica in cows infested naturally with fasciola and paramphistomum flukes. Ivermectin (10 mg / 50 kg.b.wt. S/C) showed its nematocidal activity against nematodes in cows infested naturally with some nematodes and paramphistomum flukes . Ricobendazole given concomitantly with Ivermectin exert a fasciolicidal and nematocidal activities in cows infested with fasciola, nematodes and paramphistomum flukes. Both drugs each alone and their concomitant administration failed to reduce paramphistomum spp. eggs . B- Heamatological Findings :- Hb concentration showed a significant decrease at 2nd and 8th week from treatment in all treated cows. Lactating cows injected with Ivermectin and cows treated with Ricobendazole concomitantly with Ivermectin showed a significant increase in R.B.Cs. count at 4th and 8th week from treatment. R.B.Cs. count in cows treated with Summary 391 Ricobendazole showed a significant decrease during all periods of the experiment. PCV level showed a significant increase at 4th and 8th week from treatment in all treated cows . W.B.Cs. count showed a significant decrease at 2nd, 4th and 8th week from treatment in all treated cows. Lymphocyte count showed a significant decrease at 8th week from treatment in all treated cows. Monocyte count showed a significant decrease at 2nd ,4th and 8th week from treatment in all treated cows. Granulocyte count showed a significant increase at 2nd and 8th week from treatment in all treated cows as compared with the same cows before treatment. C-Biochemical findings :- 1-Liver function tests : Ricobendazole and Ivermectin each alone induced a significant increase in AST level at 2nd and 4th week from treatment. ALT showed a significant increase at 4th week from treatment in all treated cows. ALP level showed a significant increase at 8th week from treatment in all treated cows .TSB level showed a significant increase at 2nd and 4th week from treatment in all treated cows. Total protein level showed a significant decrease at 2nd and 8th week from treatment in all treated cows . Cholesterol level showed a significant increase at 2nd week from treatment in all treated cows as compared with the same cows before treatment. 2-Renal function tests . Urea and createnine levels showed insignificant changes at 2nd, 4th and 8th week from the beginning of drug administration as compared with the same cows before treatment. |