title: Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis.
abstract: Neuroinflammation and angiogenesis have been involved in the pathogenesis of Parkinson's disease (PD). This study investigated the effect of ibuprofen or piroxicam on the motor response to l-dopa and development of dyskinesia in Parkinsonian rats focusing on the anti-angiogenic role of the two non-steroidal anti-inflammatory drugs (NSAIDs). Rats were divided into nine groups as follows: Group I: the vehicle group, Group II: rotenone group, rats were injected with nine doses of rotenone (1 mg/kg/48 h), group III&IV: rats received rotenone + ibuprofen (10 or 30 mg/kg), Group V-VI: rats received rotenone + piroxicam (1 or 3 mg/kg), Group VII: rats received rotenone + l-dopa/carbidopa (100/10 mg/kg), Group VIII-IX: rats received rotenone + l-dopa/carbidopa + ibuprofen (30 mg/kg) or piroxicam (3 mg/kg). In general, drugs were administered daily for ten weeks. Rotenone-treated rats showed motor dysfunction, lower striatal dopamine, lower staining for nigral tyrosine hydroxylase but higher level of striatal cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) compared to vehicle-treated rats (P < 0.05). Treatment with l-dopa showed wearing-off over the course of the experiment in addition to development of abnormal involuntary movements and upregulated striatal VEGF level. Treatment with ibuprofen or piroxicam in combination with l-dopa preserved the effect of l-dopa at the end of week 10, delayed the development of dyskinesia and decreased striatal COX-2 and VEGF levels. In conclusion, the current study suggests that ibuprofen and piroxicam are promising candidates for neuroprotection in PD and may have utility in conjunction with l-dopa in order to ensure the longevity of its action and to delay the development of dyskinesia.
authors.affiliation: Al Azhar University Hospital, Damietta, Egypt.
authors.forename: Asmaa M
authors.initials: AM
authors.lastname: Teema
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. Electronic address: Sawsan_zaytoon@pharm.suez.edu.eg.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Moustafa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D007980:Levodopa / Q000633:toxicity*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D010894:Piroxicam; D007980:Levodopa; D007052:Ibuprofen
keywords: Angiogenesis; Dyskinesia; Ibuprofen; Parkinsonism; Piroxicam; Rat; l-dopa