Effects of creatine in a rat intestinal model of ischemia/reperfusion injury

PURPOSE: Creatine belongs to a buffering system of cellular ATP level and has been reported to display direct antioxidant activity. Aim of this work was to investigate whether creatine treatment could ameliorate the antioxidant response of intestinal cells and limit the oxidative injury induced by anoxia and subsequent reoxygenation. METHODS: Jejunal and ileal tracts of rat intestine were everted and incubated in vitro under normoxic, anoxic and reoxygenation conditions in the absence and in the presence of 10 mM creatine. (Na+, K+)-ATPase, γ-GT and antioxidant enzymes activities were determined in mucosal homogenate, as well as malondialdehyde production and HSP70 expression. RESULTS: Both in jejunum and ileum, creatine treatment increases (Na+, K+)-ATPase activity; γ-GT is unaffected in jejunum but stimulated in ileum. In both tissues, creatine does not alter the antioxidant activities or malondialdehyde level. HSP70 expression is increased only in jejunum. Anoxic conditions stimulate antioxidant activities to a greater extent in jejunum compared to ileum; reoxygenation does not evoke further effects, but enhances malondialdehyde production in both tracts. The protective action of creatine, in reoxygenation, is more marked in jejunum as for its stimulation of antioxidant activities; however, in jejunum, a prooxidant action of creatine is suggested, since malondialdehyde production is enhanced by its presence; on the contrary in ileum, where HSP70 is overexpressed in reoxygenation, peroxidation level is significantly reduced. CONCLUSIONS: The presence of creatine seems to potentiate the defensive response of both tissues, in jejunum by means of cell antioxidant equipment, in ileum by the involvement of HSP70.