title: Dose-dependent neuroprotective effect of caffeine on a rotenone-induced rat model of parkinsonism: A histological study.
abstract: Several lines of evidence have demonstrated an inverse relationship between caffeine utilization and Parkinson's disease (PD) progression. Caffeine is a methylxanthine known as a non-specific inhibitor of adenosine (A2A and A1) receptors in the cerebrum and demonstrated to be a neuroprotective medication. In this study, the neuroprotective efficacy of two different doses of caffeine ranging above the usual consumption dose and below the toxic dose was investigated using histopathological and immunohistochemical methods. Thirty-two male rats were randomly divided into 4 groups, with 8 in each group: vehicle control (1ml/kg/48h for 12 days), rotenone (1.5mg/kg/48h, s.c. for 12 days), low-dose Caffeine-treated: (10mg/kg IP. daily for 12 days), high-dose Caffeine-treated (20mg IP daily for 12 days). Twenty-four hours after the last rotenone injection, animals were sacrificed and brains were sectioned and prepared for histopathological staining with hematoxylinand eosin, cresyl violet and Mallory's phosphotungestic acid haematoxylinand for immunohistochemical staining of tyrosine hydroxylase. Our study showed that the treatment with caffeine improved histopathological degeneration in the substantia nigra parts compacta (SNpc) neurons and hindered the reduction in dopamine concentration caused by rotenone. We also found that a higher dose of caffeine was more effective against histopathological degeneration. These results suggest that caffeine has a dose-dependent neuroprotective effect.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: amiram.soliman_pgs@med.suez.edu.eg.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Soliman
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Fathalla
authors.affiliation: Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, USA; School of Social Sciences and Psychology & Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia. Electronic address: a.moustafa@westernsydney.edu.au.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Moustafa
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D065842:Pars Compacta / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D012402:Rotenone
chemical_list: D018696:Neuroprotective Agents; D012402:Rotenone; D002110:Caffeine
keywords: Histological stains; Immunohistochemical; Parkinson’s disease; Rotenone model