title: The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats.
abstract: 3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington's disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions. Rats administered 3-NP (20mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity. Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain-Shams University, Monazamet Al-Wehdah Al-Efrikeya St., Abbassia, Cairo 11566, Egypt. ebamahdy111@yahoo.com
authors.forename: Heba M
authors.initials: HM
authors.lastname: Mahdy
authors.forename: Mariane G
authors.initials: MG
authors.lastname: Tadros
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mohamed
authors.forename: Amr M
authors.initials: AM
authors.lastname: Karim
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D020441:Ginkgo biloba / Q000737:chemistry; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000627:therapeutic use*; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000096983:Ginkgo Extract
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D010936:Plant Extracts; D011422:Propionates; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C015392:3-nitropropionic acid