Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1βand IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT andNfe2l2/AREpathways in the liver.

Glutathione redox cycle enzymes as potential targets for heme-mediated oxidation under hemolysis: in silico analysis

Glutathione (g-glutamylcysteinylglycine) redox homeostasis in human erythrocytes is dependent on the activities of glutathione peroxidase (GPX1, EC 1.11.1.9), glutathione reductase (GSR, EC 1.8.1.7), glutaredoxin 1 (GRX1) and NADPH-generating enzymes of pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGD, EC 1.1.1.44). Free heme accumulation under hemolysis can affect proteins activity thereby in silico analysis of glutathione redox cycle enzymes structure was performed in order to reveal putative heme-binding sites and oxidizable cysteine residues. Protein annotations were taken from UniProt. Heme docking was performed by PatchDock with clustering RMSD 1,5 Å using PDB structures of proteins and heme. Cysteines oxidation potential was estimated by Cy-Preds. Heme binding GSR monomers (1DNC, 3DJJ, 3DK9, 2GRT) and dimers (3SQP, 2GH5) was predicted through His81 close to interchain disulfide bond and through Cys59 near FAD and GSSG binding sites. Heme-binding areas in GPX1 (2F8A) and GPX3 (2R37) also were revealed in the interchain region and in active centre (His80). GLRX1 (4RQR) was predicted to bind heme almost exclusively near the N-end in spite of accessibility of all cysteines including CPYC motif in active centre. G6PD monomer (2BH9, 5UKW) revealed heme-docking areas in NADP+ binding region and a-helix 437–447 located in dimer 2BHL at the interchain surface. Heme docking to PGD (4GWG, 4GWK) was in substrate binding region near His187. So enzymes active centres and chain interaction regions were revealed in the most of heme docking variants. From one (in PGD) to three (GSR) cysteines susceptible to oxidation were found in each protein including cysteines that were predicted to bind heme. Heme-mediated oxidative effect on glutathione redox cycle enzymes in erythrocytes and blood plasma could be an important mechanism of hemolysis progression under stress and pathologies.

Riboflavin (vitamin B2) and oxidative stress: a review

Oxidative stress is involved in the development of many chronic diseases. One of the main factors involved in oxidative stress reduction is increased antioxidant potential. Some nutrients such as vitamin C, vitamin E and carotenoids are known to act as antioxidants; however, riboflavin is one of the neglected antioxidant nutrients that may have an antioxidant action independently or as a component of the glutathione redox cycle. Herein, studies that have examined the antioxidant properties of riboflavin and its effect on oxidative stress reduction are reviewed. The results of the reviewed studies confirm the antioxidant nature of riboflavin and indicate that this vitamin can protect the body against oxidative stress, especially lipid peroxidation and reperfusion oxidative injury. The mechanisms by which riboflavin protects the body against oxidative stress may be attributed to the glutathione redox cycle and also to other possible mechanisms such as the conversion of reduced riboflavin to the oxidised form.