Comparison of the efficacy of the mouse hepatic and renal antioxidant systems against inflammation-induced oxidative stress.

This study was conducted to compare the efficacy of the mouse hepatic and renal antioxidant systems against inflammation-induced oxidative stress. Increased Il-1 and Il-6 expressions, markers of inflammation, were represented by inflammation models in mouse liver and kidney tissues injected intraperitoneally with LPS. After establishing the model, the GSH level and the GSH/GSSG ratio, which are oxidative stress markers, were investigated in both tissues treated with LPS and the control group. The expression of Trx1, TrxR, and Txnip genes increased in the liver tissues of LPS-treated mice. In the kidney tissue, while Trx1 expression decreased, no change was observed in TrxR1 expression, and Txnip expression increased. In the kidneys, TRXR1 and GR activities decreased, whereas GPx activity increased. In both tissues, the TRXR1 protein expression decreased significantly, while TXNIP expression increased. In conclusion, different behaviors of antioxidant system members were observed during acute inflammation in both tissues. Additionally, it can be said that the kidney tissue is more sensitive and takes earlier measures than the liver tissue against cellular damage caused by inflammation and inflammation-induced oxidative stress.

Coaction of hepatic thioredoxin and glutathione systems in iron overload-induced oxidative stress.

In the present study, we demonstrate the coaction of thioredoxin and glutathione (GSH) systems in mouse liver against iron overload-induced oxidative stress (OS). Mice were injected intraperitoneally with an iron dextran solution twice a week for 3 weeks. Iron accumulation in mouse liver was demonstrated spectroscopically. To confirm the iron overload model in the liver, the increased gene expression levels of hepcidin (Hamp), ferroportin (Fpn1), and ferritin (Fth1), which regulate iron trafficking, were observed by a quantitative polymerase chain reaction. In the case of iron overload, the GSH level and the reduced glutathione/oxidized glutathione ratio, which represents a marker of OS, decreased significantly. An increase in the malondialdehyde level, one of the final products of the lipid peroxidation process, was observed. The gene expression of the thioredoxin system, including thioredoxin (Trx1) and thioredoxin reductase (TrxR1), was examined. Though TrxR1 expression decreased, no changes were observed in Trx1. The enzyme activity and semiquantitative protein expression of TRXR1 increased. The activity of GSH reductase and GSH peroxidase increased in the iron overload group. The gene and protein expressions of thioredoxininteracting protein, which is an indicator of the commitment of the cell to apoptosis, were elevated significantly. The increased protein expression of Bcl-2-related X protein and CASPASE-3, which is an indicator of apoptosis, increased significantly. In conclusion, excess iron accumulation in mouse liver tissue causes OS, which affects the redox state of the thioredoxin and GSH systems, inducing cell apoptosis and also ferroptosis due to increased lipid peroxidation and the depletion of GSH level.