Hemin treatment abrogates monocrotaline-induced pulmonary hypertension

K. Shimzu, Takatoru Takahashi, Tatsuo Iwasaki, H. Shimizu, K. Inoue, Hiroshi Morimatsu, E. Omori, M. Matsumi, R. Akagi, K. Morita

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 μmol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-α and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.

Original languageEnglish
Pages (from-to)572-576
Number of pages5
JournalMedicinal Chemistry
Volume4
Issue number6
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Monocrotaline
Hemin
Pulmonary Hypertension
Heme Oxygenase-1
Pneumonia
Lung
Pyrrolizidine Alkaloids
Inflammation
Ventricular Pressure
Heme
Chlorides
Oxidative Stress
Neutrophils
Theoretical Models
Tumor Necrosis Factor-alpha
Gene Expression

Keywords

  • Heme oxygenase-1
  • Hemin
  • Inflammation
  • Monocrotaline
  • Pulmonary hypertension
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Hemin treatment abrogates monocrotaline-induced pulmonary hypertension. / Shimzu, K.; Takahashi, Takatoru; Iwasaki, Tatsuo; Shimizu, H.; Inoue, K.; Morimatsu, Hiroshi; Omori, E.; Matsumi, M.; Akagi, R.; Morita, K.

In: Medicinal Chemistry, Vol. 4, No. 6, 11.2008, p. 572-576.

Research output: Contribution to journalArticle

Shimzu, K, Takahashi, T, Iwasaki, T, Shimizu, H, Inoue, K, Morimatsu, H, Omori, E, Matsumi, M, Akagi, R & Morita, K 2008, 'Hemin treatment abrogates monocrotaline-induced pulmonary hypertension', Medicinal Chemistry, vol. 4, no. 6, pp. 572-576. https://doi.org/10.2174/157340608786241972
Shimzu, K. ; Takahashi, Takatoru ; Iwasaki, Tatsuo ; Shimizu, H. ; Inoue, K. ; Morimatsu, Hiroshi ; Omori, E. ; Matsumi, M. ; Akagi, R. ; Morita, K. / Hemin treatment abrogates monocrotaline-induced pulmonary hypertension. In: Medicinal Chemistry. 2008 ; Vol. 4, No. 6. pp. 572-576.
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