Glutathione depleting drugs, antioxidants and intestinal calcium absorption

Abstract

Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

Effect of Dietary Supplementation With Mixed Organic Acids on Immune Function, Antioxidative Characteristics, Digestive Enzymes Activity, and Intestinal Health in Broiler Chickens

“…Glutathione peroxidase (GSH-Px) is involved in converting between reduced glutathione and oxidized glutathiol, reduced H 2 O 2 to H 2 O, and lipid peroxides to alcohols. Total antioxidant capacity (T-AOC) was used as an indicator of the overall antioxidant capacity of the organism ( 47 , 48 ). In our research, diets with HMOA supplementation enhanced the content of SOD and CAT in the serum of 21 and 42 d-broiler, respectively, and the level of T-AOC, SOD, and CAT were increased in serum of 42 d-broiler fed with LMOA.…”

Characterization and Duodenal Transcriptome Analysis of Chinese Beef Cattle With Divergent Feed Efficiency Using RNA-Seq

“…The intestinal tract is the primary organ controlling these processes. The duodenum-the first digestive and absorptive organ of the intestinal tract-is vital for the absorption of glucose (Zhong et al, 2020), fat (Everard et al, 2019), vitamin B (Wang et al, 2019), calcium (Moine, 2018), zinc (Zhong et al, 2020), and iron (Andrews, 2008). Therefore, to better understand how the duodenum and its functions are associated with RFI phenotypes.…”

Quercetin Alleviates Oxidative Damage by Activating Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Porcine Enterocytes

“…As previous reports shown, quercetin is a flavonoid aglycone that has 3-OH groups and inhibits the formation of chain oxidation and terminates chain propagation in ROS production [ 51 ]. GSH-related redox homeostasis regulated by Nrf2 signaling is also an important contributes against oxidative injury in enterocytes [ 52 ]. As previous study shown, diquat was found to increase the oxidized glutathione (GSSG) content, decrease the GSH content, and increased the ratio of GSSG/GSH in the intestine of piglets [ 39 ], and similar results were also observed in our in vitro studies.…”