Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 2011
MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress.
Accumulating evidence suggests that endogenous dopamine may act as a neurotoxin and thereby participate in the pathophysiology of Parkinson's disease (PD). Cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of PD due to its ability to generate reactive oxygen species (ROS). Inhibition of COX-2 leads to neuroprotection by preventing the formation of dopamine-quinone. ⋯ Reserpine, a dopamine-depleting agent, significantly reduced VM neurotoxicity induced by MPP(+), whereas dopamine had an additive effect on MPP(+)-induced VM neurotoxicity and VM dopaminergic cell apoptosis. However, inhibition of COX-2 by a selective COX-2 inhibitor (DFU) or ibuprofen significantly attenuated MPP(+)-induced VM cell toxicity and VM dopaminergic cell apoptosis, which was accompanied by a decrease in ROS production in VM dopaminergic neurons. These results suggest that dopamine itself mediates MPP(+)-induced VM neurotoxicity and VM dopaminergic cell apoptosis in the presence of COX-2.
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Naunyn Schmiedebergs Arch. Pharmacol. · May 2011
Glutamine contributes to ameliorate inflammation after renal ischemia/reperfusion injury in rats.
The aim of this study was to investigate the effects of glutamine in an in vivo rat model of renal ischemia/reperfusion (I/R) injury. Male Wistar rats underwent bilateral renal pedicle clamping for 45 min followed by reperfusion for 6 h. Glutamine (1.5 mg/kg) was administered intraperitoneally (i.p.) 15 min prior to reperfusion. ⋯ Glutamine reduced the histological evidence of renal damage associated with I/R and caused a substantial reduction in the staining for nitrotyrosine and PARS, suggesting reduced nitrosative and oxidative stress. Moreover, glutamine attenuated the reduction of COX-2 expression and prevented the increased AT-1 expression after I/R. Our results suggest that glutamine reduces the renal dysfunction and injury associated with I/R of the kidney.
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Naunyn Schmiedebergs Arch. Pharmacol. · May 2011
Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with L-NAME-induced hypertension.
Inhibition of nitric oxide synthesis with N ( ω )-nitro-L-arginine methyl ester (L-NAME) induces marked hypertension and oxidative stress. Curcumin (CUR) has been shown strong antioxidant property. Tetrahydrocurcumin (THU), a major metabolite of CUR, possesses several pharmacological effects similar to CUR; however, it is less studied than CUR. ⋯ Moreover, CUR and THU reduced vascular superoxide production, decreased oxidative stress, and increased the previously depressed blood glutathione (GSH) and the redox ratios of GSH in L-NAME hypertensive rats. The antihypertensive and some antioxidant effects of THU are apparently more potent than those of CUR. This study suggests that CUR and THU prevented the development of vascular dysfunction induced by L-NAME and that the effects are associated with alleviation of oxidative stress.
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Naunyn Schmiedebergs Arch. Pharmacol. · Mar 2011
ReviewTherapeutic effects of Clostridium botulinum C3 exoenzyme.
C3 exoenzyme from Clostridium botulinum, specifically ADP-ribosylates small GTP-binding proteins RhoA, B, and C. ADP-ribosylation causes functional inactivation of Rho proteins resulting in cessation of the complete downstream signaling. Rho proteins are general regulators of a lot of essential cellular functions, among others, the neuronal growth cone. ⋯ Whereas full-length C3 also acts on astrocytes and microglia to induce-at least in an in vitro model-inflammation and glial scar formation, C3(154-182) peptide is inert and seems only to act on neurons. In addition to its axono- and dendritotrophic effects on cultured primary hippocampal neurons, C3(154-182) peptide enhanced functional recovery and regeneration in a mouse model of spinal cord injury. Thus, in a proof-of-principle experiment, C3 peptide was shown to be efficacious in post-traumatic neuro-regeneration.
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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 2010
Ivabradine in patients with inappropriate sinus tachycardia.
Inappropriate sinus tachycardia (IST) is characterized by paroxysmal tachycardia originating in the sinus nodal area. IST predominately affects young, female patients. Current antiarrhythmic drug treatment (ß-blockers, calcium antagonists), frequently complicated by side effects, is often not successful. ⋯ Three patients reported transient phosphene-like phenomena without discontinuation of ivabradine while on therapy. IST-associated symptoms were ameliorated (3 pts) or suppressed (5 pts) in all eight patients who could be contacted after a mean follow-up of 16 ± 9 months. Ivabradine appears effective and safe in patients with symptomatic inappropriate sinus tachycardia.