Cyclosporine A inhibits acetylcholinesterase activity in rats experimentally demyelinated with ethidium bromide (original) (raw)
Related papers
Cyclosporine A inhibits acetylcholinesterase activity in selected parts of the rat brain
Neuroscience Letters, 2003
Cyclosporine A (CsA) is the major immunosuppressive drug used for organ and neural transplantation and the therapy of selected autoimmune diseases. We investigated the effect of CsA on the activity of acetylcholinesterase (AChE) in the frontal cortex, hippocampus, septum, and basal ganglia. AChE was determined spectrophotometrically with acetylthiocholine as substrate and 5,5-bis-2-nitrobenzoic acid as chromogen. CsA was administered in single doses of 20 or 45 mg/kg perorally; in the case of the higher dose we also performed a repeated administration of CsA in three consecutive doses separated by 24 h intervals. Both lower and higher doses of CsA decreased AChE activity in the frontal cortex and hippocampus to practically the same extent. On the contrary, AChE activity was more diminished in the case of the higher dose of CsA used in the septum and basal ganglia. Repeated administration of the higher dose of CsA did not lead, with the exception of the hippocampus, to a further decrease in AChE activity in the brain structures observed. These findings contribute to rare evidence concerning the interaction of CsA and the cholinergic system in the brain. q
Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové, 2002
The aim of this work is a comparison of single and repeated peroral administration of cyclosporine (CsA) and the interaction of repeated administration of CsA and 7-methoxytacrine (MEOTA) on the activity of acetylcholinesterase (AChE) in the frontal cortex, hippocampus, septum, and basal ganglia in rats. Both single and repeated administration of CsA diminished the activity of AChE in the frontal cortex, septum and basal ganglia, while the enzyme activity in the hippocampus was diminished only in the case of repeated CsA, as well as repeated CsA + MEOTA administration. Repeated administration of CsA led to a further augmentation of anticholinesterase activity only in the frontal cortex and--in a lesser extent--in the basal ganglia. No augmentation of AChE activity was observed in the hippocampus and septum.
Neurochemical Research, 2006
The ethidium bromide (EB) demyelinating model was associated with interferon beta (IFN-β) to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC), cerebellum (CB), hypothalamus (HY), pons (PN) and synaptosomes from the CC. Rats were divided into four groups: I control (saline), II (IFN-β), III (EB) and IV (EB and IFN-β). After 7, 15 and 30 days rats (n = 6) were sacrificed, and the brain structures were removed for enzymatic assay. AChE activity was found to vary in all the brain structures in accordance with the day studied (7–15–30 days) (P < 0.05). In the group III, there was an inhibition of the AChE activity in the ST, CB, HY, HP and also in synaptosomes of the CC (P < 0.05). It was observed that IFN-β per se was capable to significantly inhibit (P < 0.05) AChE activity in the ST, HP, HY and synaptosomes of the CC. Our results suggest that one of the mechanisms of action of IFN-β is through the inhibition of AChE activity, and EB could be considered an inhibitor of AChE activity by interfering with cholinergic neurotransmission in the different brain regions.
Journal of Neuroimmunology, 1999
Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by inoculation with myelin basic protein (MBP) and adjuvants. Rats were treated with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease followed by clinical recovery. Rats treated with CsA 16 or 32 mg/kg had minimal signs of EAE at the usual time after inoculation, but developed signs of disease after treatment was ceased. Rats treated with CsA 8 mg/kg had a delayed first episode of disease and then developed a relapsing or a chronic persistent course of disease. CsA 4 mg/kg delayed the onset of disease. To study the effects of CsA on the inflammatory infiltrate, cells were extracted from the spinal cords of rats with EAE, 16 h after a single injection of CsA or saline. Extracted cells were labelled with antibodies to T cells, CD11b/c (macrophages/microglia), CD95 (Fas) and Fas ligand. CsA 4 mg/kg did not alter the composition of the inflammatory infiltrate. Treatment with higher single doses of CsA caused a dose-dependent decline in the percentage of T cell receptor (TCR) + cells in the inflammatory infiltrate. All doses of CsA caused a significant increase in the number and percentage of cells that were apoptotic. CsA treatment caused an increase in the percentages of CD5 + and TCR + cells that were apoptotic. There was a decline in the percentage of apoptotic T cells that were V 8.2 + , compared to the percentage of nonapoptotic T cells that were V 8.2 + , in CsA treated rats compared to saline-treated controls. This suggests that, while CsA treatment caused a non-specific increase in the overall level of T cell apoptosis in the spinal cord, it abrogated the selective apoptosis of V 8.2 + encephalitogenic T cells that normally occurs during spontaneous recovery from acute EAE.
The effect of dichlorvos on acetylcholinesterase activity in some tissues in rats
Acta veterinaria, 2010
In this study, the changes with respect to time in the serum, brain, liver, kidney and small intestine acetylcholinesterase activities were investigated in both male and female rats administered dichlorvos intraperitoneally (i.p.). For this purpose, 4 mg kg-1 doses of dichlorvos were injected i.p. in the rats. The control groups, on the other hand, were administered physiological saline via the same route. Rats were killed by decapitation at 0, 2, 4, 8, 16, 32, 64 and 72 hours after administration of dichlorvos and tissues were harvested. Enzyme activities were determined following the necessary treatments. While a significant decrease in enzyme activities in the kidney and small intestine tissues with respect to time were not observed in either sex, a significant decrease in enzyme activities in the serum, as well as in the brain and liver tissues were observed. As a result of our study, acetylcholinesterase activity was found to be decreased compared to controls in both male and female rats from 2 and 4 hours. Enzyme inhibition continued for up to 72 hours.
Journal of Autoimmunity, 1992
The therapeutic effect of the ether phospholipid SRI 62-834, which lacks the characteristics of an immunosuppressive agent, was compared with those of two immunosuppressive drugs, cyclosporin and valine'dihydrocyclosporin, in a rat model of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Drug treatment was initiated at the beginning of the first spontaneous remission on day 15 and was discontinued on day 31. Whereas the untreated rats experienced two paralytic relapses around days 21 and 31, the progression of CR-EAE was prevented during the period of drug administration. Protection with both cyclosporin and its derivative was complete, but SRI 62-834 only attenuated the clinical disease. The absence of paralytic symptoms was reflected by a distinct reduction in mononuclear cell infiltration in the central nervous system at days 21 and 31 in treated animals. The main difference between the two drug classes became apparent after withdrawal of therapy. Discontinuation of SRI 62-834 resulted in a long-lasting beneficial effect, with the rats remaining clinically normal and showing no histopathological changes. However, cyclosporin only delayed the clinical symptoms which reappeared after cessation of treatment. The exacerbated paralytic relapse, which followed about 1 week later and was associated with severe perivascular cell infiltrates and tissue destruction, subsequently became chronic in several animals. By contrast, withdrawal of valine'dihydrocyclosporin partially prevented disease relapse and markedly
Toxicological Sciences, 1996
Neurotoxicity and Pattern of Acetylcholinesterase Inhibition in the Brain Regions of Rat by Bromophos and Ethylbromophos. SANTHOSHKUMAR, P., KARANTH, S., AND SHIVANANDAPPA, T. (1996). Fundam. Appl. Toxicol. 32,[23][24][25][26][27][28][29][30] and ethylbromophos (EBp) are two structurally homologous organophosphorus (OP) insecticides which show wide differences in their toxicity as well as neurotoxic symptoms in the laboratory rat. EBp is 24-fold more toxic (LD50 = 91 ± 14 mg/kg body wt) than Bp (LD50 = 2218 ± 195 mg/kg body wt) and only EBp produced characteristic tremors and lacrimation. In vivo cholinesterase inhibition was in the order plasma > erythrocytes > brain. Experiments with equitoxic and equimolar doses showed that EBp is a more potent anticholinesterase compound than Bp. Since ICSO values for the brain AChE were similar for both OPs, the target enzyme sensitivity was not a major factor in their differential toxicity. In vitro reactivation of serum ChE was significantly higher in the case of EBp than that of Bp. AChE in the brain regions showed differential inhibition in vivo. The brain stem AChE inhibition was least by Bp, whereas it was highest in the case of EBp. Both the OPs produced high AChE inhibition in the hippocampus. Differential inhibition of AChE in the brain regions and its consequent effects may be important factors in the differential neurotoxicity of OPs. © 1996 society of Toxi col ogy