الفهرس Only 14 pages are availabe for public view
 |  | from | 143 |  |  |
| | | from | 143 | | |
Abstract
Closantel and nitroxynil are widely used as fasciolicidal drugs. Studies were carried on both isolated tissues and intact animals to show their effects.
I- The results obtained on isolated organs revealed:
1-Closantel induced inhibitory effect on rabbit duodenum at concentration of 0.2-0.3 mg/ml. At concentration 0.4 mg/ml induced complete relaxation.
2-Nitroxynil induced stimulation on rabbit duodenum at concentration of 0.1-0.2 mg/ml where as at concentration 0.4 mg/ml induced marked stimulation.
3-Closantel induced inhibition of isolated rat uterine muscle contraction in both force and frequency at concentration of 0.2-0.3 mg/ml. Complete relaxation occurred at concentration of 0.5 mg/ml.
4-Nitroxynil caused inhibition of isolated rat uterine muscle contraction at concentration of 0.2-0.3 mg/ml.
5-Closantel in concentration of 60-80 ug/ml induced stimulatory effect on contraction of fasciola gigantica where as the drug at concentration of 100 ug/ml induced paralysis of fluke.
6-Nitroxynil induced stimulatory effect on contraction of fasciola gigantica at comcentration of 100-120 ug/ml. The drug induced paralysis of the fluke at concentration of 140 ug/ml.
II- The results on intact animal revealed that:
1-Neither closantel at doses 0.54 and 1.08 mg/100 gm b.wt. nor nitroxynil at 0.23 and 0.46 mg/100 gm b. wt. had any significant effect on feverish body temperature of rats.
2-Neither closantel at doses 0.54 and 1.08 mg/100 gm b.wt. nor nitroxynil at 0.23 and 0.46 mg/100 gm b. wt. had any significant analgesic effect.
3-Neither closantel at doses 0.54 and 1.08 mg/100 gm b.wt. nor nitroxynil at 0.23 and 0.46 mg/100 gm b. wt. had any significant effect on sleeping time of thiopental anaesthetized mice.
4-Closantel at dose 1.08 mg/100 gm b. wt. exerted significant anti-inflammatory effect after 3 and 6 hours with percentage of decrease 13.2%. On the otherhand nitroxynil had significant anti-inflammatory effect.
5-The LD50 of closantel was 15.25 mg/100 gm b. wt. in mice. while the LD50 of nitroxnil was 6.5 mg/100 gm. b. wt.
6-The repeated administration of closantel for 8-successive weeks in rats at doses 0.54 and 1.08 mg/100 gm b. wt. caused significant decrease in PCV% after 2nd, 4th and 6th weeks. Concerning Hb. concentration showed significant decrease at dose of 0.54 mg/100 gm b. wt. after 4th and 8th weeks but the dose 1.08 mg/100 gm b. wt. had significant decrease after 8th week. W.B.Cs. count showed significant decrease after 2nd week at 0.54 mg/100 gm b. wt. while after 8th week showed significant decrease at both 0.54 and 1.08 mg/100 gm b. wt. doses. R.B.Cs. count showed significant decrease after 4th week at 0.54 and 1.08 mg/100 gm b. wt. doses.
7- On the other hand nitroxynil at 0.23 and 0.46 mg/100 gm b. wt. caused significant decrease in PCV% after 4th week but after 2nd week only higher dose caused significant decrease. But the small dose showed significant decrease after 6th week. Hb. Concentration showed significant decrease after 4th week at 0.23 and 0.46 mg/100 gm. b. wt. doses. W.B.Cs count revealed significant increase after 2nd week at 0.23 and 0.46 mg/100 gm. b. wt. doses while after 8th week high dose caused significant decrease.
8-Neither closantel at doses 0.54 and 1.08 mg/100 gm b.wt. nor nitroxynil at 0.23 and 0.46 mg/100 gm b. wt. had any significant changes on differential leucocytic counts.
9-The repeated administration of closantel at doses 0.54 and 1.08 mg/100 gm b.wt. caused significant increase in AST and ALT enzymes activity after 6th and 8th weeks. Also, nitroxynil at doses 0.23 and 0.46 mg/100 gm b.wt. caused significant increase in AST and ALT enzyme activity after 6th and 8th weeks.
10- The repeated administration of closantel at doses 0.54 and 1.08 mg/100 gm b.wt. caused significant increase in urea level after 8th week, while nitroxynil at doses 0.23 and 0.46 mg/100 gm b.wt. caused no significant changes in urea and creatinine levels.
11-The repeated administration of closantel in rats weekly for 8-weeks at higher doses caused degenerative changes in the liver especially at the periphery of the hepatic lobules and some Von Kuppfer cells occasionally were seen. The lower dose led to milder changes in the liver such as mild congestion of the blood vessels, leucocytic infiltration was focally seen in some rats. The kidneys showed moderate to severe changes at higher doses of closantel such as glomerulonephrosis, degenerative changes and congestion of blood vessels. These changes were very mild when lower doses were used. The heart and the spleen had some degenerative changes only when the higher dose was used.
12- On the other hand, repeated administration of nitoxynil in rats daily for 8 weeks resulted in moderate changes in liver at higher dose, but the changes were very mild at small doses. Also the kidneys showed some degenerative changes at high dose and a very mild change at small dose. The heart and the spleen at higher dose had very mild changes, but at smaller doses they revealed no pathological alterations.