CD Skripsi

efek antiinflamasi sapropterin terhadap nitric oxide synthase 3, cox-2, il-10, dan mikrovaskularisasi pada tikus model hemoroid

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Hemorrhoids are anorectal disorders characterized by venous dilation and mucosal inflammation. Recent genomic analyses identify nitric oxide synthase-3 (NOS3) as a key risk gene; sapropterin—an FDA-approved 6-R-tetrahydrobiopterin analog for phenylketonuria—is predicted to down-regulate this pathway.
Objective: To evaluate the anti-inflammatory effect of sapropterin on NOS3, cyclo-oxygenase-2 (COX-2), and interleukin-10 (IL-10) expression, Plasma IL-10 concentration, and microvascular changes in a rat model of hemorrhoids.
Methods: A true-experimental post-test-only design was employed with 20 male Sprague-Dawley rats (250–350 g) in which hemorrhoids were induced using 6 % croton oil. Animals were allocated to five groups: normal control, negative control, positive control (aspirin 1 mg kg⁻¹ day⁻¹), sapropterin 0.3 mg kg⁻¹ day⁻¹, and sapropterin 0.6 mg kg⁻¹ day⁻¹ (oral, 7 days). mRNA levels of NOS3, COX-2, and IL-10 were quantified by qRT-PCR (2⁻ΔΔCt method); Plasma IL-10 by ELISA; tissue COX-2 and IL-10 protein by immunohistochemistry (H-score); anorectal venule diameter on H&E sections using ImageJ. One-way ANOVA with Tukey post-hoc test was applied (α = 0.05).
Results: Hemorrhoid induction up-regulated NOS3 (4.4-fold) and COX-2 (16.1-fold) and enlarged venules (0.624 ± 0.132 mm). Sapropterin significantly reduced NOS3 (to 0.010-fold) and COX-2 (~1.8-fold), narrowed venule diameter (0.282 ± 0.123 mm), and dose-dependently increased tissue IL-10 (H-score 133–165). Plasma IL-10 concentrations decreased (~21–23 pg mL⁻¹), indicating attenuation of systemic inflammation. All effects were comparable to or exceeded those of aspirin.
Conclusions: Sapropterin modulates the NOS3/COX-2/IL-10 axis and ameliorates microvascular pathology in experimental hemorrhoids, highlighting its potential as a targeted anti-inflammatory repurposing candidate. These findings warrant further pre-clinical development and suggest a new molecular therapeutic avenue for hemorrhoid management.
Keywords: hemorrhoids, sapropterin, nitric oxide synthase-3 (NOS3), cyclo-oxygenase-2 (COX-2), interleukin-10 (IL-10), anti-inflammatory, drug repurposing.

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Ketersediaan

Informasi Detail

Judul Seri

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No. Panggil

2110247752

Penerbit

Pekanbaru : Universitas Riau – PASCA – Magister Ilmu Biomedis., 2025

Deskripsi Fisik

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Bahasa

Indonesia

ISBN/ISSN

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Klasifikasi

2110247752

Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

Magister Ilmu Biomedis

Info Detail Spesifik

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Pernyataan Tanggungjawab

Rahmat

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