الفهرس 
Review of literatureOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Colchicine is a toxic natural product and secondary metabolite, originally extracted from plants of the genus colchicum. It was used originally to treat rheumatic complaints, especially gout, and still finds use for these purposes today despite dosing issues concerning its toxicity. It was also prescribed for its cathartic and emetic effects. Colchicine’s present medicinal use is in the treatment of gout, familial Mediterranean fever, pericarditis and Behçet’s disease. It is also being investigated for its use as an anti-cancer drug. Colchicine is a microtubule disrupting agent that binds to tubuline, inhibiting microtubule assembly which triggers apoptosis. Colchicine triggers apoptosis in several neuronal in vitro models such as granular neuronal culture (CGN). Mood stabilizing drugs as, lithium, used in the treatment and prophlaxis of bipolar disorders, show neuroprotective effects against colchicine induced apoptosis in rat cerebellar granular neurons. This study demonstrate that the activation of caspase-3 by colchicine is inhibited in the presence of lithium. All these findings confirm earlier reports and are in line with evidence that lithium exerts wide neuroprotective and anti-apoptotic effects in a number of neuronal models. The present study was carried out to investigate the effects of colchicine on the cerebellum of albino rats pups and the role of lithium chloride against colchicine`s toxicity in both in vivo and in vitro models. 132 Summary & Conclusion The albino rats were choosen for this work where the offspring albino rats were kept on breast feeding with their mothers in healthy conditions from the first day of life. - Material: Fifty 7-days old albino rat offisprings were used for in vivo studies with average weight 30 grams, and twenty five primary cultures of cerebellar granular neurons (CGNs) were also prepared from 7-days old albino rat offisprings. In vivo studies: they were divided as follows: Control group (A): thirty offsprings of albino rats 7-days old were used and divided into two subgroups: a) Negative control subgroup (subgroup A1): was consisted of ten offsprings received nothing allover the experimental period. After 7 days (one week), five of them were anaesthetized lightly with ether then sacrificed, the other five were sacrificed after 3 weeks by the same method. b) Positive control subgroup (subgroup A2): was consisted of twenty offsprings and divided as follows: 1- Vehicle control subgroup: was consisted of ten offsprings, each of them was treated with 1 ml distilled water (the solvent of colchicine) intraperitoneally for one day then no treatment was given. After 7 days, five of them were anaesthetized lightly with ether then sacrificed, the other five were sacrificed after 3 weeks by the same method. 2- Lithium chloride treated control subgroup: was consisted of ten offsprings, each of them was treated only with 133 Summary & Conclusion lithium chloride 40 mg/kg body weight dissolved in 1 ml distilled water intraperitoneally for 7 days. After these 7 days, five of them were anaesthetized lightly with ether then sacrifced, the other five were sacrificed after 3 weeks by the same method. Colchicine treated group (B): was consisted of ten 7-days old rats, they received 4 mg/kg body weight colchicine dissolved in 1ml distilled water once by intraperitonial injection. After 7 days, five of them were anaesthetized lightly with ether then sacrificed, the other five were sacrificed after 3 weeks by the same method. Lithium chloride and Colchicine treated group (C): was consisted of ten 7-days old rats, they received 4 mg/kg body weight colchicine dissolved in 1ml distilled water once by intraperitonial injection, then they received daily dose of lithium chloride 40mg/kg body weight dissolved in 1 ml distilled water intraperitonially for 7 days. After these 7 days, five of them were anaesthetized lightly with ether then sacrificed, the other five were sacrificed after 3 weeks by the same method. -Methods: Rats were sacrificed according to the time schedule mentioned before. The cerebella were dissected and subjected to the following studies: *Histological study, using haematoxylin and eosin staining. Also by toluidine blue staining. Immunohistochemical study, using caspase-3 enzyme. Morphometric studies. 134 Summary & Conclusion They were divided into the following groups:In vitro studies: Control group (A): Fifteen cultures were formed in this group from 7 days old albino rat offsprings and divided into two subgroups: a) Negative control subgroup (subgroup A1): contained five cultures obtained from 7 days old albino rat offsprings. After 7 days in vitro, CGNs cultures were kept without any additions and served as control for all in vitro experimental groups. b) Positive control subgroup (subgroup A2): contained ten cultures and divided as follows: 1- Vehicle control subgroup: contained five cultures obtained from 7 days old albino rat offsprings. After 7 days in vitro, CGNs cultures were incubated for 24 hours in complete medium containing 5 ml distilled water. 2- Lithium chloride treated control subgroup: contained five cultures obtained from 7 days old albino rat offsprings. After 7 days in vitro, CGNs cultures were incubated for 24 hours in complete medium containing lithium chloride (5mM).