In order to understand the lack of suppression of the suckling rat excretion rate of CO (VeCO) by tin-protoporphyrin (TP), except in association with broad-spectrum antibiotics [Posselt, et al. AJDC 140:147-150, 1986], we studied the role of intestinal CO sources in this model. The production of CO (VCOgut) by homogenates of Wistar rat intestine is highest in the suckling ileum, decreasing proximally; the gradient is reversed in the adult. After a single 25 umole TP/kg SQ dose, causing significant inhibition of hepatic and splenic heme oxygenase (HO), no difference in the VCOgut between saline- and TP-treated adults was observed. In sucklings, only the duodenal VCOgut was slightly reduced (p<.05).
Treatment with ampicillin, kanamycin, and neomycin, with or without TP (up to 65 umole/kg), also did not suppress the VCOgut of adult or suckling rats. We conclude: 1) TP, at a dose which inhibits hepatic and splenic HO in adult and suckling rats, may not significantly decrease VCOgut; 2) the suppression of the suckling VeCO by TP and antibiotics cannot be explained by antibiotic-mediated inhibition of intestinal HO; 3) because heme is excreted into the intestine after TP treatment, the suppression of the VeCO by TP in adult rats suggests a comparatively decreased capacity of intestinal bacteria to produce CO.
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Stevenson, D., Kim, C., Hintz, S. et al. UNDERSTANDING CO PRODUCTION BY SUCKLING RATS AFTER TIN-PROTOPORPHYRIN THERAPY: INTESTINAL SOURCES OF CO. Pediatr Res 21, 242 (1987) doi:10.1203/00006450-198704010-00448