Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism
ABSTRACT Parkinson's disease (PD) is a neuropathological and debilitating disorder involving the degeneration of mesencephalic dopaminergic neurons. Neuroprotective effect of pelargonidin (Pel) has already been reported, therefore, this study examined whether Pel administration would attenuate behavioural and structural abnormalities and markers of oxidative stress in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5mug/5mul of saline-ascorbate)-lesioned rats were pre-treated p.o. with Pel (10 and/or 20mg/kg). Pel administration dose-dependently attenuated the rotational behavior in lesioned rats and protected the neurons of SNC against 6-OHDA toxicity. In addition, pre-treatment with Pel (20mg/kg) significantly decreased the 6-OHDA-induced thiobarbituric acid reactive substances (TBARS) formation, indicative of a neuroprotection against lipid peroxidation. Furthermore, the increase of nitrite levels induced by 6-OHDA, indicate the nitric oxide formation and free radicals production and the decrease of antioxidant defense enzyme superoxide dismutase (SOD) was non-significantly prevented by Pel (20mg/kg). In summary, Pel administration has a dose-dependent neuroprotective effect against 6-OHDA toxicity, partly through attenuating oxidative stress. Our findings suggest that pelargonidin could provide benefits, along with other therapies, in neurodegenerative disorders including PD.
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- "Now, connection between DA activity and gastroduodenal ulcer disease is well established  . A number of pharmacological agents have now been designed and tested that showed protective role against brain dysfunctioning  , but whether they have antiulcer activity that remains to be investigated other than our paper . Previously, we have shown that a drug A68930 has antistress activity in acute and chronic unpredictable stress models . "
ABSTRACT: For decades, it has been suggested that dysfunction of dopaminergic pathways and their associated modulations in dopamine levels play a major role in the pathogenesis of neurological disorders. Dopaminergic system is involved in the stress response, and the neural mechanisms involved in stress are important for current research, but the recent and past data on the stress response by dopaminergic system have received little attention. Therefore, we have discussed these data on the stress response and propose a role for dopamine in coping with stress. In addition, we have also discussed gastric stress ulcers and their correlation with dopaminergic system. Furthermore, we have also highlighted some of the glucocorticoids and dopamine-mediated neurological disorders. Our literature survey suggests that dopaminergic system has received little attention in both clinical and preclinical research on stress, but the current research on this issue will surely identify a better understanding of stressful events and will give better ideas for further efficient antistress treatments.Advances in Pharmacological Sciences 09/2012; 2012:182671. DOI:10.1155/2012/182671
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ABSTRACT: Aspects of error performance of the land mobile satellite system (LMSS) using QPSK (quaternary phase-shift keying) and MSK (minimum shift keying) under fading channel conditions have been studied. In contrast to the sole use of average bit-error rate (BER) as a performance measure, bit-by-bit-error rates are calculated for the sequence of transmitted data under various fading conditions by computer simulation. For this purpose, various measured data from field experiments are collected and processed to yield the scaled version of fade amplitudes and phases for several data transmission cycles. Under the condition of a moving vehicle at a speed of 55 m.p.h. at 850-MHz transmission, a series of 256-b data streams at the rate of 2.4 kb/s are simulated using coherent QPSK and MSK. A total of 203.2 wavelength fade data is used to give actual fading effects. Results show that bit-by-bit error under fast varying fade can predict the exact location of error bits among the sequence of transmitted data, which cannot be done by using average BERMilitary Communications Conference, 1989. MILCOM '89. Conference Record. Bridging the Gap. Interoperability, Survivability, Security., 1989 IEEE; 11/1989
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ABSTRACT: The neuroactive metabolite at the kynunerine pathway, kynurenic acid (KYNA), is a well-known competitive antagonist at the co-agonist glycine site of the N-methyl-D-aspartate receptor (NMDAr), and also decreases the extracellular levels of glutamate by blocking α7-nicotinic acetylcholine receptor (α7-nAchr) located on glutamatergic terminals. KYNA has been often reported to be neuroprotective in different neurotoxic models. The systemic administration of L-kynurenine (L-KYN)--the precursor of KYNA--together with probenecid (PROB)--an inhibitor of organic acids transport--to rodents increases KYNA levels in the brain in a dose-dependent manner. The striatal infusion of the toxin 6-hydroxydopamine (6-OHDA) to rodents is one of the common models used to simulate Parkinson's disease (PD). Different studies have linked PD alterations with excessive glutamatergic transmission in the striatum since NMDAr antagonists exert beneficial effects in PD models. In this work we investigated the effect that a systemic administration of L-KYN+PROB exerted on the toxic model induced by 6-OHDA in rats. PROB (50 mg/kg, i.p.) + L-KYN (75 mg/kg, i.p.) were given to rats for seven consecutive days. On day two of treatment, the animals were infused with a single injection of 6-OHDA (20 μg/2 μl) into the right striatum. Fourteen days post-lesion, rotation behavior was assessed as a marker of motor impairment. The total levels of dopamine (DA) were also estimated in striatal tissue samples of 6-OHDA-treated animals as a neurochemical marker of damage. In addition, twenty eight days post-lesion, the striatal damage was assessed by hematoxylin/eosin staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) in the same animals. Neurodegeneration was also assessed by Fluoro Jade staining. 6-OHDA infusion increased rotation behavior, striatal reactive gliosis and neurodegeneration, while DA levels were decreased. For all markers evaluated, we observed protective effects of L-KYN+PROB on the dopaminergic damage induced by 6-OHDA. Our results suggest that this strategy was useful to mitigate dopaminergic toxicity in the hemiparkinsonian model. The combined use of L-KYN and PROB is a valuable tool to modulate glutamatergic and cholinergic activities, presumably by means of increased levels of endogenous KYNA.Neurotoxicology and Teratology 10/2010; 33(2):303-12. DOI:10.1016/j.ntt.2010.10.002 · 3.22 Impact Factor