Background and Aims: Recent studies have shown that daily use of NSAIDs, frequently causes small intestinal ulcers and
erosions. However, effective drugs to prevent aspirin/NSAIDs-induced small intestinal lesions have not been developed. In the present
study, we examined the effects of sulforaphane (SFN), a substance rich in broccoli sprouts, on aspirin/NSAIDs-induced small intestinal
Methods: 1. In vitro study: IEC6 cells, derived from rat small intestinal mucosae, were incubated with or without SFN. The cells were
subsequently exposed to aspirin. In some experiments, the effect of zinc protoporphyrin-IX (ZnPP), 0.1 μM, an inhibitor of heme oxygenase-
1 (HO-1), was also examined. 2. In vivo study: IND-induced small intestinal mucosal injury was induced in male ddY mice. SFN
glucosinolates (SGS), which is glucosinolates precursor of SFN, was orally administered to the mice, at dose of 17 mg/mouse, before and
after the injection of IND. Vascular permeability was assessed by measuring the amount of exudated Evans Blue in the mucosa, which
had been injected intravenously. Neutrophil activation was evaluated by myeloperoxidase (MPO) activity. Amount of mucosal anaerobic
bacteria was also measured.
Results: 1. In vitro study: (1) SFN, 5 μM, significantly attenuated aspirin (20 mM)-induced cell injury. (2) SFN enhanced HO-1 expression
in IEC-6 cells. The protective effect of SFN against aspirin-induced injury was attenuated by 0.1 μM ZnPP. 2. In vivo study: (1) IND
treatment caused mucosal injury in small intestine, increased vascular permeability, enhanced MPO activity, and augmented mucosal invasion
of anaerobic enterobacteria. (2) SGS attenuated the IND-induced small intestinal injury. (3) SGS prevented the IND-induced increase
in mucosal invasion of anaerobic enterobacteria.
Conclusions: These results suggest that SFN protects small intestine from aspirin / NSAIDs-induced injury, presumably by up-regulating
nrf2-keap1 dependent antioxidant system and by inhibiting invasion of anaerobic bacteria into the mucosa.