Glutathione depleting drugs, antioxidants and intestinal calcium absorption

Table 1 Glutathione depletion and the intestinal calcium absorption

	Oxidative stress markers	Effect on intestinal Ca2+ absorption
BSO	↓GSH	↓Ca2+ transfer from lumen-to-blood
MEN	↓GSH ↑ROS and protein carbonyl ↑Mn2+-SOD and GPX Mitochondrial dysfunction	↓Ca2+ transfer from lumen-to-blood ↓IAP and PMCA1b activities
NaDOC	↓GSH ↑ROS	↓Intestinal Ca2+absorption
	Mitochondrial swelling.	↓mRNA PMCA1b
	↑SOD, CAT and GPX	↓PMCA1b, CBD28k and NCX1 protein expression
	↑NO• ↑iNOS protein
FRD	↓GSH ↑.O2−	↓Intestinal Ca2+ absorption
	↑protein carbonyl and nitrotyrosine content	↓IAP activity
	↓SOD and CAT	↓TRPV6, PMCA1b, CBD9k, CLDN 2, CLDN12 and VDR protein expression
	↑NO•

BSO: DL-buthionine-S,R-sulfoximine; CAT: Catalase; CB_D28k: Calbindin D28k; CB_D9k: Calbindin D9k; CLDN 2: Claudin 2; CLDN12: Claudin 12; FRD: Fructose rich diet; GPX: Glutathione peroxidase. GSH: Glutathione; IAP: Intestinal alkaline phosphatase. MEN: menadione. Mn²⁺-SOD: Mn²⁺-superoxide dismutase. NaDOC: sodium deoxycholate.NCX1: Na⁺/Ca²⁺ exchanger; NO•: Nitric oxide; PMCA1b: Plasma membrane Ca²⁺ATPase; SOD: Superoxide dismutase; TRPV6: Transient receptor potential vanilloid type 6; VDR: Vitamin D receptor.

Table 2 Antioxidants that preserve/ restore the inhibition of intestinal Ca²⁺ absorption caused by glutathione depletion

Drugs	Normalized OS markers	Effect on inhibition of ICaA	Normalized component of ICaA	Apoptosis markers	References
GSH monoester	GSH total	Restoration			Tolosa de Talamoni et al[21]
MEL	GSH, ˙O2− Protein carbonyl SOD, CAT and GPX activities iNOS gene and protein expression	Prevention restoration	PMCA1b, CBD9k, NCX1, CLDN 2 and CLD 12 protein expression	↓TUNEL index ↓Caspase 3 activity/protein expression	Carpentieri et al[80] Areco et al[81]
QT	GSH total. GPX activity	Prevention		↓Caspase 3 activity ↓FAS, ↓FASL. Blocks mit swelling	Marchionatti et al[52]
GLN	GSH, ˙O2−. Protein carbonyl SOD and CAT activity	Prevention restoration	CBD28k and PMCA1b protein expression.	↓TUNEL index. ↓FAS, ↓FASL ↓Caspase-3 activity	Moine et al[88]
NAR	GSH, ˙O2− NO• Protein carbonyl and nitrotyrosine content. SOD and CAT activity	Prevention	IAP activity (partially) PMCA1b, CBD9k, NCX1, VDR, CLDN2 and CLD12 protein expression		Rodríguez et al[58]
UDCA	GSH, NO• protein carbonyl SOD activity iNOS protein expression	Increase restoration	IAP activity ↑PMCA1b, CBD28k, NCX1, VDR gene and protein expression	↓Mit swelling ↓FAS, ↓FASL gene/protein content Caspase 8 protein content Caspase 3 activity	Rodríguez et al[22,48]

CAT: Catalase; CB_D28k: Calbindin D28k; CB_D9k: Calbindin D9k; CLDN 2: Claudin 2; CLDN12: Claudin 12; GLN: Glutamine; GPX: Glutathione peroxidase; GSH: Glutathione; IAP: Intestinal alkaline phosphatase; ICaA: Intestinal Ca²⁺ absorption; MEL: Melatonin; MEN: Menadione; Mit: Mitochondrial; NAR: Naringin; NCX1: Na⁺/Ca²⁺exchanger; NO: Nitric oxide; OS: Oxidative stress; PMCA1b: Plasma membrane Ca²⁺-ATPase; QT: Quercetin; SOD: Superoxide dismutase; TRPV6: Transient receptor potential vanilloid type 6; UDCA: Ursodeoxycholic acid; VDR: Vitamin D receptor.