Oxidative stress, antioxidants and intestinal calcium absorption

Abstract

The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components. When the ROS and/or RNS production is exacerbated, oxidative stress occurs and the intestinal Ca²⁺ absorption is inhibited. GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione and sodium deoxycholate inhibit the Ca²⁺ transport from lumen to blood by alteration in the protein expression and/or activity of molecules involved in the Ca²⁺ transcellular and paracellular pathways through mechanisms of oxidative stress, apoptosis and/or autophagy. Quercetin, melatonin, lithocholic and ursodeoxycholic acids block the effect of those drugs in experimental animals by their antioxidant, anti-apoptotic and/or anti-autophagic properties. Therefore, they may become drugs of choice for treatment of deteriorated intestinal Ca²⁺ absorption under oxidant conditions such as aging, diabetes, gut inflammation and other intestinal disorders.

Keywords: DL-buthionine-S,R-sulfoximine; Lithocholic acid; Melatonin; Menadione; Sodium deoxycholate; Transcellular and paracellular Ca2+pathways; Ursodeoxycholic acid.

Figure 1

Schematic representation of the possible mechanisms involved in the inhibition of intestinal Ca²⁺ absorption caused by oxidative stress. TRPV6: Transient receptor potential vanilloid 6; TRPV5: Transient receptor potential vanilloid 5; IAP: Intestinal alkaline phosphatase; GSSG: Disulfide of glutathione; GSH: Glutathione; GPx: Glutathione peroxidase; GR: Glutathione reductase; SOD: Superoxide dismutase; CAT: Catalase; Cyt c: Cytochrome c; Cldns: Claudins; iNOS: Inducible nitric oxide synthase; NCX1: Intestinal Na⁺/Ca²⁺ exchanger; PMCA1b: Plasma membrane Ca²⁺- ATPase 1b; TJ: Tight junctions.