Antioxidant and glutathione-associated enzymes in Wilms' tumour after chemotherapy

Abstract

The present study demonstrates the activities of antioxidant and glutathione-associated enzymes and the level of glutathione in Wilms' tumour (nephroblastoma) samples after chemotherapy (mainly actinomycin D and vincristine). We observed higher activity of superoxide dismutase in Wilms' tumour compared to adjacent morphologically unchanged kidney. On the other hand, in this tumour lower activities of catalase and the glutathione-associated enzymes glutathione synthetase, gamma-glutamyl transpeptidase, glutathione reductase and total glutathione S-transferases (GST) were found. Using isoelectric focusing we separated different forms of GST in tested tissues and revealed lower activities of the basic enzymes in Wilms' tumour, which may be responsible for the decrease of total GST activity. Moreover, we found the acidic isoenzymes to be the predominant class of GST in nephroblastoma. In Wilms' tumours with unfavourable histology a high activity of these isoenzymes together with a high level of GSH were observed. We suggest that these parameters may participate in the known phenomenon of anticancer drug resistance of tumours with unfavourable histology.

Dually degradable click hydrogels for controlled degradation and protein release

“…42, 43 However, the rapid rate of degradation of disulfide linkages provides limited control over material degradation and cargo release, and GSH-sensitive linkers that permit controlled extracellular delivery over days to weeks thus have been less explored. In addition, since the concentration of GSH is higher in carcinoma tissues than in healthy tissues due to abnormal proliferative activities of cancer cells, 40, 41, 44 reducing sensitive chemistries incorporated within drug delivery carriers offer great potential for localized cancer treatment. To address this need and opportunity, we present reducing microenvironment-sensitive hydrogels that undergo tunable degradation on the order of days to weeks for controlled protein delivery, demonstrating the broad utility of the click bond cleavage and thiol exchange reaction as a general strategy not only to control degradation but also to control the release of cargo molecules locally from a bioinert delivery vehicle.…”

Manganese Superoxide Dismutase-Mediated Gene Expression in Radiation-Induced Adaptive Responses

“…However, excessive ROS formation such as that seen during IR can cause cell death, and intrinsic antioxidant enzymes (AEs) are induced to protect cells from ROS-induced lethality (21). ROS have been shown to activate preapoptosis signaling elements such as JNK (66).…”

“…The protective effect of MnSOD against normal tissue damage caused by radiation is highlighted by in vivo experiments showing induction of MnSOD following radiation in the heart and gut (42,49) and the finding that overexpression of MnSOD in normal mouse epithelial tissues protected them from radiation injury (18). Endogenous SOD activity is also involved in the resistance of Wilms' tumors to chemotherapeutic agents (21) and in protecting human leukemic and cancer cells from radiation (63). Further evidence suggests that radiation-induced esophagitis is linked with activation of a group of cytokines that are responsive to MnSOD (19).…”

The effect on radioresistance of manganese superoxide dismutase in nasopharyngeal carcinoma

“…SOD2 works in concert with other antioxidant enzymes to defend cells against the damage associated with exposure to reactive oxygen species (ROS) (5) and is thought to be an important determinant of sensitivity to ROS-induced cytotoxicity. Scavenging the reactive species produced at the time of irradiation can mitigate some of the effects of IR-iduced injury.…”