The protective effects of PBN against MPTP toxicity are independent of hydroxyl radical trapping

B Ferger, Peter Teismann, C D Earl, K Kuschinsky, W H Oertel

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

To study the mechanism of the protective effect of the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity hydroxyl radicals and functional parameters of neuroprotection were determined. C57BL/6 mice received PBN (100 mg/kg IP) over a time period of 15 days and on day 8 MPTP (40 mg/kg SC). On day 15 striatal levels of dopamine, serotonin, and metabolites were analyzed. For radical determination mice received a single injection of salicylic acid (SA) (100 mg/kg IP) in the time period of 0.5 h before to 72 h after MPTP injection. In vivo maximum hydroxyl radical levels indicated by 2,3-dihydroxybenzoic acid/SA ratios were obtained 4 h after MPTP injection, and were not affected by PBN treatment. However, the MPTP-induced mortality, reduction of locomotor activity, continuous loss of body weight, and striatal dopamine depletion were significantly less pronounced in PBN-treated animals. These results elucidate the time course of hydroxyl free radical formation in MPTP toxicity. PBN improved the functional parameters of neuroprotection against MPTP toxicity, but there is no evidence for hydroxyl radical scavenging properties to this effect.
Original languageEnglish
Pages (from-to)425-431
Number of pages7
JournalPharmacology, Biochemistry & Behavior
Volume65
Issue number3
DOIs
Publication statusPublished - 1 Mar 2000

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Hydroxyl Radical
Toxicity
Corpus Striatum
Salicylic Acid
Injections
Dopamine
Spin Trapping
Scavenging
Locomotion
Metabolites
nitrones
Inbred C57BL Mouse
Free Radicals
Serotonin
Animals
Body Weight
Mortality

Keywords

  • Animals
  • Body Weight
  • Cyclic N-Oxides
  • Dopamine
  • Free Radical Scavengers
  • Hydroxyl Radical
  • MPTP Poisoning
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • Nitrogen Oxides
  • hydroxyl radicals
  • PBN
  • MPTP
  • neuroprotection
  • Parkinson's disease
  • salicylate trapping
  • radical scavenger
  • TERT-BUTYL-NITRONE
  • NEURONAL NITRIC-OXIDE
  • OXIDATIVE STRESS
  • IN-VIVO
  • NEURODEGENERATIVE DISORDERS
  • HEART-MITOCHONDRIA
  • FOCAL ISCHEMIA
  • SPIN TRAPS
  • NEUROTOXICITY

Cite this

The protective effects of PBN against MPTP toxicity are independent of hydroxyl radical trapping. / Ferger, B; Teismann, Peter; Earl, C D; Kuschinsky, K; Oertel, W H.

In: Pharmacology, Biochemistry & Behavior, Vol. 65, No. 3, 01.03.2000, p. 425-431.

Research output: Contribution to journalArticle

Ferger, B ; Teismann, Peter ; Earl, C D ; Kuschinsky, K ; Oertel, W H. / The protective effects of PBN against MPTP toxicity are independent of hydroxyl radical trapping. In: Pharmacology, Biochemistry & Behavior. 2000 ; Vol. 65, No. 3. pp. 425-431.
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T1 - The protective effects of PBN against MPTP toxicity are independent of hydroxyl radical trapping

AU - Ferger, B

AU - Teismann, Peter

AU - Earl, C D

AU - Kuschinsky, K

AU - Oertel, W H

PY - 2000/3/1

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N2 - To study the mechanism of the protective effect of the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity hydroxyl radicals and functional parameters of neuroprotection were determined. C57BL/6 mice received PBN (100 mg/kg IP) over a time period of 15 days and on day 8 MPTP (40 mg/kg SC). On day 15 striatal levels of dopamine, serotonin, and metabolites were analyzed. For radical determination mice received a single injection of salicylic acid (SA) (100 mg/kg IP) in the time period of 0.5 h before to 72 h after MPTP injection. In vivo maximum hydroxyl radical levels indicated by 2,3-dihydroxybenzoic acid/SA ratios were obtained 4 h after MPTP injection, and were not affected by PBN treatment. However, the MPTP-induced mortality, reduction of locomotor activity, continuous loss of body weight, and striatal dopamine depletion were significantly less pronounced in PBN-treated animals. These results elucidate the time course of hydroxyl free radical formation in MPTP toxicity. PBN improved the functional parameters of neuroprotection against MPTP toxicity, but there is no evidence for hydroxyl radical scavenging properties to this effect.

AB - To study the mechanism of the protective effect of the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity hydroxyl radicals and functional parameters of neuroprotection were determined. C57BL/6 mice received PBN (100 mg/kg IP) over a time period of 15 days and on day 8 MPTP (40 mg/kg SC). On day 15 striatal levels of dopamine, serotonin, and metabolites were analyzed. For radical determination mice received a single injection of salicylic acid (SA) (100 mg/kg IP) in the time period of 0.5 h before to 72 h after MPTP injection. In vivo maximum hydroxyl radical levels indicated by 2,3-dihydroxybenzoic acid/SA ratios were obtained 4 h after MPTP injection, and were not affected by PBN treatment. However, the MPTP-induced mortality, reduction of locomotor activity, continuous loss of body weight, and striatal dopamine depletion were significantly less pronounced in PBN-treated animals. These results elucidate the time course of hydroxyl free radical formation in MPTP toxicity. PBN improved the functional parameters of neuroprotection against MPTP toxicity, but there is no evidence for hydroxyl radical scavenging properties to this effect.

KW - Animals

KW - Body Weight

KW - Cyclic N-Oxides

KW - Dopamine

KW - Free Radical Scavengers

KW - Hydroxyl Radical

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KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Motor Activity

KW - Nitrogen Oxides

KW - hydroxyl radicals

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KW - MPTP

KW - neuroprotection

KW - Parkinson's disease

KW - salicylate trapping

KW - radical scavenger

KW - TERT-BUTYL-NITRONE

KW - NEURONAL NITRIC-OXIDE

KW - OXIDATIVE STRESS

KW - IN-VIVO

KW - NEURODEGENERATIVE DISORDERS

KW - HEART-MITOCHONDRIA

KW - FOCAL ISCHEMIA

KW - SPIN TRAPS

KW - NEUROTOXICITY

U2 - 10.1016/S0091-3057(99)00229-4

DO - 10.1016/S0091-3057(99)00229-4

M3 - Article

C2 - 10683482

VL - 65

SP - 425

EP - 431

JO - Pharmacology, Biochemistry & Behavior

JF - Pharmacology, Biochemistry & Behavior

SN - 0091-3057

IS - 3

ER -