ArticlePediatric surgery international2026
Alterations in biopterin metabolism and the effects of tetrahydrobiopterin supplementation in a rat model of short bowel syndrome.
Article in Pediatric surgery international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeMaintaining microcirculation via NOS function is critical for intestinal adaptation for short bowel syndrome (SBS). We investigated the dynamics of tetrahydrobiopterin (BH4), a key NOS cofactor, and the therapeutic potential of BH4 in our experimental SBS model.
methodsRats were divided into Sham (n = 18), SBS (n = 22), SBS+BH4 (n = 6), and Control (n = 4) groups. The BH4 related metabolites, NOS mRNA expression, histological parameters with hematoxylin and eosin staining, and immunohistochemistry staining with nitrotyrosine and Ki67 were analyzed in the remnant jejunum and ileum.
resultsThe SBS group exhibited significant BH4 dysregulation, marked by increased biopterin oxidation and decreased BH4/BH2 ratios, particularly in the jejunum on day 3. SBS also induced a significant upregulation of iNOS and eNOS mRNA and increased nitrotyrosine expression. The SBS+BH4 group showed a significantly preserved villus height and absorptive area in the jejunum, along with enhanced crypt cell proliferation in both the jejunum and ileum. The SBS+BH4 group effectively modulated the NOS expression and significantly reduced the nitrotyrosine levels to Sham levels.
conclusionThis study, using an SBS rat model, showed that BH4 dysregulation leads to nitrosative stress and impairs intestinal adaptation. BH4 administration can help to modulate the NOS-related pathways and maintain intestinal homeostasis.
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