Ceftriaxone mediated rescue of nigral oxidative damage and motor deficits in MPTP model of Parkinson's disease in rats

Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra pars compacta along with decreased striatal dopamine levels, and consequent extra pyramidal motor dysfunctions occur. It has been reported that Ceftriaxone, a beta-lactam antibiotic recently had shown to have neuroprotective effects in various neurodegenerative disorder. Therefore the present study was designed to investigate the effects of Ceftriaxone (CFX) in a MPTP model of Parkinson in rats. MPTP was administered intranigrally for the induction of PD in Male Wistar rats. Ceftriaxone (100 and 200 mg/kg) and Ropinirole (1.5 and 3 mg/kg) were given intraperitonially, after induction of Parkinson's disease for 14 days. Different behavioral performance was carried on 1st, 14th, 21st, 28th consecutive days and biochemical parameters were estimated on 28th day. Central administration of MPTP showed significant impairment of motor behavior and marked increase of oxidative damage and neuro-inflammmation in rats. However, post treatment with Ceftriaxone (100 and 200 mg/kg) significantly improved the motor deficits and attenuated the oxidative damage indicating decreased rise of LPO and nitrite concentration and restored the decreased activities of endogenous antioxidant enzyme (Glutathione, Catalase, SOD). In addition Ceftriaxone also attenuates the pro-inflammatory cytokines like TNF-alpha and IL-beta in striatum region of MPTP induced PD in rats. Ropinirole (1.5 mg/kg) pretreatment with sub-effective dose of a Ceftriaxone (100 mg/kg) had significantly enhanced the protective effect of Ceftriaxone as compare to its effect with per se group. These results suggested that Ceftriaxone exhibit Neuroprotective effect by mediating brain antioxidant defense mechanism and by up regulating of dopaminergic pathway and down regulation of glutamatergic pathway. (C) 2014 Elsevier Inc. All rights reserved.