Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism.
Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption. In this study, we hypothesized that low-molecular-weight, soluble zinc chelates could modulate the effects of induced NO excess on the small intestine. In vitro experiments demonstrated that zinc-citrate or zinc-histidine at > or =0.66 mM, as well as a known NO scavenger, 2-[carboxyphenyl]-4,4,4,4-tetramethylimidazoline-1-oxyl-3-oxide, at 2 microM, were effective at removing chemically generated NO. In vivo jejunal perfusions, conducted in healthy rats under anesthesia, showed that c-PTIO reduced the proabsorptive effects produced by 1 mM L-arginine, the precursor of NO. In a standard oral rehydration solution, 1 mM zinc-citrate partially reversed the antiabsorptive effects on potassium caused by an excess of NO generated from 20 mM L-arginine but did not alter sodium or water absorption. The data are consistent with the view that soluble zinc compounds incorporated into an oral rehydration solution may deserve further attention as a means to scavenge NO with fluids used for the treatment of chronic or acute diarrhea, especially in malnourished children who are often zinc deficient.
Wingertzahn
Mark A
MA
Division of Neonatal-Perinatal Medicine, Schneider Children's Hospital at North Shore, North Shore-Long Island Jewish Health System and New York University School of Medicine, Manhasset, New York, USA.
Rehman
Khalil U
KU
Altaf
Waseem
W
Wapnir
Raul A
RA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D003967:Diarrhea / Q000188:drug therapy / Q000378:metabolism; D005440:Fluid Therapy; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D000975:Antioxidants; D014867:Water; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D005947:Glucose; D015032:Zinc; D011188:Potassium