Oral zinc carnosine reduces multi-organ damage caused by gut ischemia/reperfusion in mice

Abstract

Gastrointestinal ischemia/reperfusion (I/R) injury occurs in multiple clinical situations. We examined effects of zinc carnosine (ZnC), a health food supplement claimed to possess gastrointestinal supportive activity, on I/R injury. AGS, RIE and Caco-2 cells exposed to hypoxia/normoxia (H/N) reduced cell viability by 50%. ZnC given prior- or during-hypoxia improved survival by 50–70% (p < 0.01) and truncated increase in transepithelial permeability (HRP passage) by 50% whereas carnosine or ZnSO4 were ineffective. Induction of mesenteric I/R injury in mice caused severe jejunal mucosal and lung injury, increased lipid peroxidation (MDA), inflammatory infiltration (MPO) and circulating LPS and cytokines. ZnC (58 mg/kg/day, oral 7 days) reduced injury by 50%, reduced pro-apoptotic Caspase 3, 9 and Baxα, increased Bcl2 and Hsp70, and maintained tight junction ZO1 and Claudin1 levels (all p < 0.01 vs I/R alone). ZnC shows benefit over using zinc salt or carnosine. Oral ZnC may be a useful clinical approach for I/R injury.

Keywords

• Repair
• Gut damage
• Apoptosis
• Health food supplements
• Bioactive peptide