Intestinal contact of meconium and meconium subfractions in gastroschisis upregulates serum interleukin-8 and endothelin-1

Intestinal damage induced by intraamniotic whole meconium, water and lipid soluble meconium subfractions has been well documented experimentally in gastroschisis. Previous studies have primarily focused on local mechanisms of intestinal injury, particularly the direct contact effect of meconium on the bowel surface and vasoconstrictive impact of meconium on mesenteric vascular structures. The present study aimed to evaluate the effects of whole meconium and meconium subfractions on serum Interleukin-8 (IL-8), Endothelin-1 (ET-1), Urotensin-2 (UT-2) levels and their relationship with intestinal damage. While these mediators have predominantly been investigated in terms of their local effects, this study further aimed to determine whether they can be detected in the systemic circulation through systematic blood analyses and to assess their circulating changes in association with intestinal injury. The present experimental study was conducted on Thirty-five adult female Wistar rats were randomly assigned to five groups. Intraperitoneal injections were administered daily for five consecutive days. Blood samples were collected at baseline and at 24, 72, and 144 h. Serum IL-8, ET-1, and UT-2 levels were measured using ELISA. Intestinal injury was assessed histopathologically by measuring serosal thickness. All meconium-exposed groups demonstrated significant increases in serosal thickness compared with control and sham ( p < 0.05), with the greatest increased observed in the whole meconium group. Serum IL-8 levels were significantly increased in the lipid soluble subfraction and whole meconium groups. Serum ET-1 levels were significantly increased in the water soluble subfraction and meconium groups. No significant differences were observed in serum UT-2 levels. The severity of intestinal damage remains the primary determinant of mortality and morbidity in gastroschisis. Intestinal damage was associated with IL-8 in the lipid soluble meconium subfraction, whereas vasoconstrictor related injury correlated with ET-1 in the water soluble fraction. Systemic assessment of these mediators may offer a complementary tool to evaluate the inflammatory and vasoconstrictive responses contributed by meconium exposure alongside other pathophysiological factors. Additionally, IL-8 and ET-1 may act synergistically within meconium, potentiating intestinal damage beyond that caused by individual subfractions. Despite stable systemic UT-2 levels, its local paracrine and autocrine activity may drive ET-1 elevation and intestinal injury, highlighting the need for further investigation. Not applicable (experimental study).