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


METHODS
n/a - animal and laboratory study.
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Bo
B
Li
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Carol
C
Lee
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Zechariah
Z
Martin
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Xinpei
X
Li
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Yuhki
Y
Koike
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Alison
A
Hock
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Elke
E
Zani-Ruttenstock
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Augusto
A
Zani
Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: agostino.pierro@sickkids.ca.
Agostino
A
Pierro
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D013440:Sulfides / Q000008:administration & dosage*
D015415:Biomarkers; D016207:Cytokines; D013440:Sulfides; C025451:sodium bisulfide
Hydrogen sulfide; Maternal separation; NEC; Necrotizing enterocolitis; Oxidative stress