Effects of vitamin A and C and melatonin on 3-nitrotyrosine formation in guinea pig heart under lipopolysaccharide-induced stress
Bacterial lipopolysaccharide (LPS) triggers synthesis of nitric oxide (NO) and superoxide (O2.-). O2.- can react with NO to produce the powerful oxidant peroxynitrite (ONOO-). The presence of 3-nitrotyrosine (3-NT) in tissues is often used as a marker of ONOO- production. Vitamin A, vitamin C, and melatonin are potent antioxidant molecules. We sought to clarify this issue by examining the effects of vitamin A (15,000 IU/kg/day), vitamin C (600 mg/kg/day), and melatonin (25 mg/kg) on 3-NT formation in heart tissue in a guinea pig model of LPS-induced endotoxemia. Materials and methods: A total of 75 animals were randomly divided into 5 groups (n = 15 animals for each group). 3-NT levels in the heart tissue were determined by high pressure liquid chromatography with a diode array detector. Results: In the group given LPS, 3-NT levels were significantly increased compared with the control, vitamin A + LPS-treated, vitamin C + LPS-treated, and melatonin + LPS-treated groups. In the vitamin A + LPS-treated group, vitamin C + LPS-treated group, and melatonin + LPS-treated group, 3-NT levels were similar to those of the control group. Conclusion: Vitamin A, vitamin C, and melatonin pretreatment significantly prevented 3-NT formation. These agents may offer an advantage in that they could improve the hemodynamics as well as reduce the formation of ONOO-.
Key words: Lipopolysaccharide, peroxynitrite, 3-nitrotyrosine, vitamin A, vitamin C, melatonin