ABSTRACT
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.
Subject(s)
Brain/drug effects , Dyskinesia, Drug-Induced/prevention & control , Levodopa/therapeutic use , Magnoliopsida , Parkinson Disease/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Brain/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Dyskinesia, Drug-Induced/etiology , Enkephalins/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Levodopa/administration & dosage , Levodopa/adverse effects , Levodopa/pharmacology , Male , Mice, Inbred C57BL , Movement , Parkinson Disease/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Substance P/metabolismABSTRACT
The biochemical mechanisms of Chlorella vulgaris protection against cadmium (Cd)-induced liver toxicity were investigated in male Sprague-Dawley rats (5 weeks of age, weighing 90-110 g). Forty rats were randomly divided into one control and three groups treated with 10 ppm Cd: one Cd without Chlorella (Cd-0C), one Cd with 5% Chlorella (Cd-5C), and one Cd with 10% Chlorella (Cd-10C) groups. The rats had free access to water and diet for 8 weeks. Body weight gain and relative liver weight were significantly lower in the Cd-0C group than in Cd-5C and Cd-10C groups. Rats in the Cd-0C group had significantly higher hepatic concentrations of Cd and metallothioneins (MTs) than in the Cd-5C or Cd-10C group. The hepatic MT I/II mRNA was expressed in all experimental rats. MT II was more expressed in the Cd-5C and Cd-10C groups than in the Cd-0C group. Morphologically, a higher level of congestion and vacuolation was observed in the livers of the Cd-0C group compared to those of the Cd-5C and Cd-10C groups. Therefore, this study suggests that C. vulgaris has a protective effect against Cd-induced liver damage by reducing Cd accumulation and stimulating the expression of MT II in liver. However, the details of the mechanism of C. vulgaris on liver toxicity remains to be clarified by further studies.
