nitroarginine and 2-chloropropionic-acid

nitroarginine has been researched along with 2-chloropropionic-acid* in 2 studies

Other Studies

2 other study(ies) available for nitroarginine and 2-chloropropionic-acid

ArticleYear
Possible role of nitric oxide in the development of L-2-chloropropionic acid-induced cerebellar granule cell necrosis.
    British journal of pharmacology, 1996, Volume: 117, Issue:8

    1. L-2-Chloropropionic acid (L-CPA) produces selective neuronal cell necrosis in rat cerebellum when administered orally at 750 mg kg-1 that is mediated in part through activation of N-methyl-D-aspartate (NMDA) receptors. Cerebellar granule cell death occurs between 30 and 36 h following L-CPA administration exhibiting a number of features in common with excitatory amino acid-induced cell death. We have used this in vivo model to examine the neurochemical processes following L-CPA-induced activation of NMDA receptors leading to neuronal cell death in the rat cerebellum. 2. The effects of a number of compounds which potently block nitric oxide synthase in vitro were examined on L-CPA-induced neurotoxicity 48 h following L-CPA dosing, to discover whether the neuronal cell death is mediated in part by excessive nitric oxide generation. Four inhibitors were studied, NG-nitro-L-arginine (L-NOARG), NG-nitro-L-arginine methyl ester (L-NAME), NG-iminoethyl-L-ornithine (L-NIO) and 3-bromo-7-nitroindazole (BrNI). 3. L-NAME (50 mg kg-1, i.p. twice daily) and BrIN (50 mg kg-1, i.p. twice daily) administration prevented the L-CPA-induced loss of granule cells which can reach up to 80-90% of the total cell number in rats treated with L-CPA alone. L-NOARG (50 mg kg-1, i.p. twice daily) and L-NIO administered at either 25 or 100 mg kg-1, twice daily did not produce any significant protection against L-CPA-induced neurotoxicity. 4. Both L-NAME and BrIN also prevented the L-CPA-induced increase in cerebellar water content and sodium concentrations. L-NIO when administered at the highest doses prevented the increase in cerebellar sodium concentration but not water content. L-NIO and L-NOARG were ineffective in preventing the L-CPA-induced increases in cerebellar water and sodium concentrations. 5. L-CPA-induced reductions in cerebellar aspartate and glutamate concentrations and increases in glutamine and GABA concentrations were prevented by L-NAME and BrIn, but not by L-NIO or L-NOARG. Also reductions in L-[3H]-glutamate binding to glutamate ionotrophic and metabotrophic receptors in the granule cell layer of rat cerebellum was prevented by L-NAME and BrIN, but not L-NIO or L-NOARG. 6. In conclusion, the neuroprotection offered by L-NAME and BrIN suggests that L-CPA-induced cerebellar granule cell necrosis is possibly mediated by or associated with excessive generation of nitric oxide. The inability of nitric oxide synthase inhibitors, L-NOARG and L-NIO to afford protectio

    Topics: Animals; Aspartic Acid; Cerebellum; gamma-Aminobutyric Acid; Glutamic Acid; Glutamine; Hydrocarbons, Chlorinated; In Vitro Techniques; Indazoles; Male; Necrosis; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroarginine; Ornithine; Propionates; Rats

1996
Evidence for mediation of L-2-chloropropionic acid-induced delayed neuronal cell death by activation of a constitutive nitric oxide synthase.
    British journal of pharmacology, 1996, Volume: 119, Issue:2

    1. Delayed neuronal cell death elicited by excess excitatory amino acid concentrations has been strongly implicated in many neurological disorders including head trauma, stroke, motor neurone disease and Huntington's disease. We have used the neurotoxin, L-2-chloropropionic acid (L-CPA) to model cellular events in vivo leading to delayed neuronal cell loss which is confined to the cerebellar cortex and can be prevented by inhibitors of nitric oxide synthase such as NG-nitro-L-arginine methyl ester. 2. Experiments were performed to determine whether the constitutive nitric oxide synthase (NOS) or inducible form of NOS (iNOS) was responsible for the neuronal cell death. Activation of NOS was confirmed by a 39% increase in cerebellar total nitrate and nitrite concentrations in L-CPA-treated brains, as compared to controls (controls = 2.53 +/- 0.10; L-CPA treated = 3.51 +/- 0.31 nmol mg-1 protein, P < 0.01 Student's t tests, n = 6, mean +/- s.e.mean). Biochemical measurements of total NOS activity were made in homogenates of cerebellum 6 h and 48 h following L-CPA administration, times at which L-CPA concentrations are maximal in brain and a time when there is a high proportion of cerebellar granule cell death, respectively. NOS activity as measured by the amount of [3H]-arginine converted to [3H]-citrulline, did not reveal any difference between controls (rats dosed with water) and animals dosed with L-CPA at either 6 or 48 h following dosing. Furthermore the ability of three NOS inhibitors, NG-nitro-L-arginine, 7-bromo-3-nitroindazole and S-methylisothiourea to block the conversion of [3H]-citrulline to [3H]-arginine was identical at 6 and 48 h time points in control and L-CPA treated rats. 3. Quantitative autoradiography using [3H]-NG-nitro-L-arginine was used to measure the relative anatomical distribution and amount of NOS enzyme in the cerebellum of controls and L-CPA-treated rats 48 h following dosing. There was no significant alteration in the binding of [3H]-NG-nitro-L-arginine to granular and molecular layers of the cerebellum of control and L-CPA-treated rat brains. 4. Western blotting using antibodies against the inducible NOS enzyme failed to detect the protein in cerebellums of L-CPA-treated rats when measured 48 h after L-CPA dosing. 5. In conclusion, the increase in cerebellar nitrate/nitrite concentrations in L-CPA-treated rats provides further evidence for activation of NOS in the cerebellum following administration of L-CPA. The failure to

    Topics: Animals; Autoradiography; Blotting, Western; Cell Death; Cerebellar Diseases; Cerebellum; Enzyme Activation; Enzyme Induction; Hydrocarbons, Chlorinated; Isoenzymes; Male; Neurons; Nitrates; Nitric Oxide Synthase; Nitrites; Nitroarginine; Propionates; Rats

1996