Intestinal epithelial injury induced by maternal separation is protected by hydrogen sulfide.

PURPOSE: Oxidative stress has been implicated in the pathogenesis of various neonatal diseases involving the intestine. Hydrogen sulfide (H2S) has been shown to protect against oxidative stress. We hypothesized that administration of sodium hydrosulfide (NaHS), an H2S donor, to neonatal mice can decrease the intestinal epithelial injury associated with maternal separation (MS). METHODS: C57BL/6 mice received either intraperitoneal phosphate buffered saline (PBS; n=10) or NaHS (1mg/kg/day; n=10), followed by MS for 3h daily between postnatal day P5 and P9. Control neonatal mice were untreated and were not exposed to MS (n=10). Proximal colon was harvested and analyzed for crypt length, goblet cell number per crypt, oxidative stress and inflammation. Groups were compared using one-way ANOVA with Bonferroni post-test. RESULTS: Compared to controls, MS+PBS mice had shorter crypt lengths, fewer goblet cells per crypt, reduced glutathione peroxidase activity, increased expression of thiobarbituric acid reactive substances and inducible nitric oxide synthase mRNA, as well as increased IL-6, TNFα and myeloperoxidase. Administration of NaHS significantly counteracted these negative effects of MS. CONCLUSIONS: H2S protects the colon from the epithelial damage, oxidative stress and inflammation caused by maternal separation. This study provides insights on the pathogenesis of neonatal bowel diseases and indicates the potential for a pharmacological intervention to rescue the colonic epithelium. LEVEL OF EVIDENCE: n/a - animal and laboratory study.