Resveratrol Induces Pro-oxidant Effects and Time-Dependent Resistance to Cytotoxicity in Activated Hepatic Stellate Cells

Abstract

Resveratrol (RSV) is known for its antioxidant properties; however, this compound has been proposed to have cytotoxic and pro-oxidant effects depending on its concentration and time of exposure. We previously reported the cell cycle arrest effect of low doses of RSV in GRX cells, an activated hepatic stellate cell model. Here, we evaluated the effects of RSV treatment (0.1-50 μM) for 24 and 120 h on GRX viability and oxidative status. Only treatment with 50 μM of RSV reduced the amount of live cells. However, even low doses of RSV induced an increased reactive species production at both treatment times. While being diminished within 24 h, RSV induced an increase in the SOD activity in 120 h. The cellular damage was substantially increased at 24 h in the 50 μM RSV-treated group, as indicated by the high lipoperoxidation, which may be related to the significant cell death and low proliferation. Paradoxically, this cellular damage and lipoperoxidation were considerably reduced in this group after 120 h of treatment while the surviving cells proliferated. In conclusion, RSV induced a dose-dependent pro-oxidant effect in GRX cells. The highest RSV dose induced oxidative-related damage, drastically reducing cell viability; but this cytotoxicity seems to be attenuated during 120 h of treatment.

Resveratrol and Loratadine Effects on Oxidative Stress Induced by Experimental Inflammation

“…In the liver, both GSH and GSSG are reduced, with the significantly increase of GSH/GSSG ratio. The glutathione increase in comparison with glutathione disulfide, in our experiment, is in concordance with the study that was made by Martins et al [8] using resveratrol in activated hepatic stellate cells, that established that this polyphenol does not induce GSH oxidation. The significant decrease of GSH in the liver is realized through the GSH action against the reactive oxygen species (e.g.…”

Combination of diminazene aceturate and resveratrol reduces the toxic effects of chemotherapy in treating Trypanosoma evansi infection

“…High levels of FRAP were also observed in animals treated with DA in association with RSV; therefore, the use of RSV in association with DA had no nephroprotective effect. Martins et al (2014) related that RSV induced a dose-dependent pro-oxidant effect in GRX cells, where a high dose induced oxidative-related damage, reducing cell viability. Thus, we believe that the increase of FRAP has been beneficial for the animals, since resveratrol has several protective actions.…”

Resveratrol cytotoxicity is energy‐dependent

“…In support of this idea, it has been reported that resveratrol supplementation of NHEK cells prompted a hormetic behavior in the transcription of catalase, which fits well with the cellular viability of these cells (Plauth et al, ). Resveratrol supplementation (50 µM) and incubation for 120 hr decreased cell viability in liver fiber granulomas (GRX) cells, increased ROS generation, and augmented superoxide dismutase activity (Martins et al, ). An increase in the activity of superoxide dismutase accompanied by a decrease in ROS production was also observed in isolated rat liver mitochondria with 50 µM of resveratrol (Valdecantos, Perez‐Matute, Quintero, & Martinez, ).…”