Stability, disposition, and penetration of catalytic antioxidants Mn-porphyrin and Mn-salen and of methylprednisolone in spinal cord injury

Liqin Wu, Yichu Shan, Danxia Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This study measured the time courses of concentration changes following administration of the catalytic antioxidants Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and Mn (III) 3-methoxy N, N' bis (salicyclidene) ethylenediamine chloride (EUK-134) in blood and cerebrospinal fluid (CSF) of rats with a spinal cord injury (SCI) and sham controls. Parallel measurements were made for methylprednisolone, the only drug presently used clinically for treating SCI. The time courses kinetically characterized the agents in their stability, disposition, and ability to penetrate the blood-spinal cord barrier (BSB). In both the SCI and control groups, MnTBAP was stable in CSF and in blood across the collection periods (10 h and 24 h, respectively) following administration. In the blood, [EUK-134] and [methylprednisolone] rapidly declined to near basal concentrations at 4 h and 2 h, respectively, post-administration. Therefore the order of stability in CSF and blood was MnTBAP ≫ EUK-134 > methylprednisolone. The maximum CSF/blood concentration ratios for EUK-134, methylprednisolone and MnTBAP post-administration were: 32 ± 3.1%, 19.2 ± 6.4%, and 4.42 ± 0.73% in the injured rats, and 22 ± 6.5%, 17.8 ± 2.9%, and 1.0 ± 0.5% in the sham control animals. This suggests an order of BSB penetration of EUK-134 > methylprednisolone ≫ MnTBAP. Despite much lower penetration by MnTBAP compared with EUK-134 and methylprednisolone, a lower dose of MnTBAP because of its stability provided a higher concentration in CSF than did the other agents given at higher doses. This finding supports further exploration of MnTBAP as a potential treatment for SCI.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalCentral Nervous System Agents in Medicinal Chemistry
Volume12
Issue number2
StatePublished - Jun 2012

Fingerprint

Porphyrins
Methylprednisolone
Spinal Cord Injuries
Antioxidants
Cerebrospinal Fluid
ethylenediamine
Spinal Cord
Mn-salen
manganese(III)-tetrakis(4-benzoic acid)porphyrin
EUK-134
Chlorides
Control Groups
Pharmaceutical Preparations

Keywords

  • Antioxidant therapy
  • Blood-spinal cord barrier
  • EUK-134
  • Methylprednisolone
  • Mn-containing catalytic antioxidants
  • MnTBAP
  • Spinal cord injury
  • Stability and disposition

ASJC Scopus subject areas

  • Molecular Medicine
  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

Cite this

Stability, disposition, and penetration of catalytic antioxidants Mn-porphyrin and Mn-salen and of methylprednisolone in spinal cord injury. / Wu, Liqin; Shan, Yichu; Liu, Danxia.

In: Central Nervous System Agents in Medicinal Chemistry, Vol. 12, No. 2, 06.2012, p. 122-130.

Research output: Contribution to journalArticle

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abstract = "This study measured the time courses of concentration changes following administration of the catalytic antioxidants Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and Mn (III) 3-methoxy N, N' bis (salicyclidene) ethylenediamine chloride (EUK-134) in blood and cerebrospinal fluid (CSF) of rats with a spinal cord injury (SCI) and sham controls. Parallel measurements were made for methylprednisolone, the only drug presently used clinically for treating SCI. The time courses kinetically characterized the agents in their stability, disposition, and ability to penetrate the blood-spinal cord barrier (BSB). In both the SCI and control groups, MnTBAP was stable in CSF and in blood across the collection periods (10 h and 24 h, respectively) following administration. In the blood, [EUK-134] and [methylprednisolone] rapidly declined to near basal concentrations at 4 h and 2 h, respectively, post-administration. Therefore the order of stability in CSF and blood was MnTBAP ≫ EUK-134 > methylprednisolone. The maximum CSF/blood concentration ratios for EUK-134, methylprednisolone and MnTBAP post-administration were: 32 ± 3.1{\%}, 19.2 ± 6.4{\%}, and 4.42 ± 0.73{\%} in the injured rats, and 22 ± 6.5{\%}, 17.8 ± 2.9{\%}, and 1.0 ± 0.5{\%} in the sham control animals. This suggests an order of BSB penetration of EUK-134 > methylprednisolone ≫ MnTBAP. Despite much lower penetration by MnTBAP compared with EUK-134 and methylprednisolone, a lower dose of MnTBAP because of its stability provided a higher concentration in CSF than did the other agents given at higher doses. This finding supports further exploration of MnTBAP as a potential treatment for SCI.",
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