[The protective effects and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats].

Abstract

OBJECTIVE:

To investigate the protective effect and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP-cyclohydrolase I (GTP-CHI), on postburn Staphylococcus aureus (S. aureus) sepsis in rats.

METHODS:

Fifty-six Wistar rats were randomly divided into four groups, i.e. normal control, scalding control, postburn sepsis group and DAHP treatment group. Tissue samples from liver, kidneys, lungs and heart were aseptically taken, and in which the GTP-CHI and inducible nitric oxide synthase (iNOS) contents and the mRNA expression of tumor necrosis factor-alpha (TNFalpha) were determined. Furthermore, biopterin (BH(4)) and nitric oxide (NO) levels in these tissue were also measured.

RESULTS:

After the scalding injury followed by bacterial challenge, the GTP-CHI gene expression and biopterin levels were significantly increased in all tissue sampled, and so were iNOS mRNA expression and NO (P < 0.01), especially in liver and lungs. The expressions of GTP-CHI mRNA and iNOS mRNA and the production of BH(4) and NO in all tissue were evidently inhibited by the pretreatment with DAHP (P < 0.05 approximately 0.01). At the same time, the TNFalpha expression was also obviously decreased. In addition, The mortality at 6 hr in rats of DAHP treatment group was decreased.

CONCLUSION:

The prognosis of the scalding rats complicated by sepsis caused by G(+) bacteria could be improved by DAHP pretreatment, which might be related to the inhibition of the production of BH(4) and NO by DAHP.

• Authors: Yongming Yao, Hongyun Li, Ning Dong, Yan Yu, Lianrong Lu, Zhiguo Shi, Zhiyong Sheng
• Journal: Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns (Zhonghua Shao Shang Za Zhi) Vol. 18 Issue 2 Pg. 84-7 (Apr 2002) ISSN: 1009-2587 [Print] China
• PMID: 12515652 (Publication Type: English Abstract, Journal Article)

Chemical References

• 5-dehydro-3-deoxy-D-arabino-heptulosonic acid-7-phosphate
• Enzyme Inhibitors
• Hypoxanthines
• RNA, Messenger
• Sugar Acids
• Tumor Necrosis Factor-alpha
• Biopterin
• Nitric Oxide
• Nitric Oxide Synthase
• GTP Cyclohydrolase
• 2,4-diaminohypoxanthine

Topics

• Animals
• Biopterin (metabolism)
• Burns (complications, genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• GTP Cyclohydrolase (antagonists & inhibitors, genetics)
• Gene Expression Regulation (drug effects)
• Heart (drug effects)
• Hypoxanthines (pharmacology)
• Kidney (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Lung (drug effects, metabolism)
• Male
• Myocardium (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (genetics)
• RNA, Messenger (drug effects, genetics, metabolism)
• Rats
• Rats, Wistar
• Sepsis (etiology, prevention & control)
• Staphylococcal Infections (etiology, prevention & control)
• Staphylococcus aureus (drug effects, growth & development)
• Sugar Acids
• Time Factors
• Tumor Necrosis Factor-alpha (genetics)