Thiol supplementation in aged animals alters antioxidant enzyme activity after heat stress

Abstract

Declines in oxidative and thermal stress tolerance are well documented in aging systems. It is thought that these alterations are due in part to reductions in antioxidant defenses. Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging, where the reliance on antioxidant enzymes and proteins may be altered. To determine whether thiol supplementation improved the antioxidant enzyme profile of aged animals after heat stress, young and old Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h before heat stress. Liver tissue was collected before and 0, 30, and 60 min after heat stress. Aging was associated with a significant decline in tissue cysteine and glutathione (GSH) levels. There was also an age-related decrease in copper-zinc superoxide dismutase activity. Heat stress did not alter liver GSH, glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old animals took up more cysteine than young animals as reflected in an increase in liver GSH and a corresponding decrease in glutamate cysteine ligase activity. Catalase activity increased after NAC treatment in both age groups. Copper-zinc superoxide dismutase activity did not change with heat stress or drug treatment, whereas manganese superoxide dismutase activity was increased in old animals only. These data indicate that GSH synthesis is substrate limited in old animals. Furthermore, aged animals were characterized by large fluctuations in antioxidant enzyme balance after NAC treatment, suggesting a lack of fine control over these enzymes that may leave aged animals susceptible to subsequent stress.

Role of Antioxidants in Dermal Aging: An In Vitro Study by q-RT-PCR

“…Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging. NAC treatment has a role not only in GSH activity, but in increased catalase and mitochondrial manganese superoxide dismutase activities [16]. NAC has an immunologic modulator role and not an indiscriminate stimulating effect.…”

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

“…In phase 2 of the study, a subset of animals ( n = 24) receiving combined RF ablation and liposomal doxorubicin therapy was used to examine the outcomes of blocking the effects of cellular stress. N -acetylcysteine (NAC) (American Regent, Shirley, NY), a thiol antioxidant ( 35 ), was administered at a dose of 300 mg per kilogram of body weight by using intraperitoneal injection ( n = 12) at 24 hours and 1 hour prior to RF application. Tissues were harvested at 30 minutes, 60 minutes, and 4 hours after ablation (four animals at each time point) and examined for evidence of 8-OHdG, NT, and cleaved caspase-3.…”

Influence of acute heat stress on the development of GABAergic neurons in HPA-axies of mouse embryos

“…This indicates that the antioxidant enzyme is not destroyed during the acute heat stress. This indication is also proved by a rat study, which found the enzyme activity and the severity affected by additional exposure to acute stresses depend on the affected brain region and the type of stress (Morrison et al, 2005;Pejić et al, 2006). The immobilization stress increases the CuZnSOD activity in the hippocampus and the cortex while the cold stress decreases its activity in these regions.…”