ABSTRACT
Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated rats was significantly lower than that in the sepsis-induced rats. RA treatment also decreased the MDA levels and increased the GSH levels and SOD and GSH-Px activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-α level was found to be decreased in the RA-treated rats. It seems that RA might have a role in the attenuation of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing the antioxidant status and DNA repair capacity of the animals.
Subject(s)
Antioxidants/therapeutic use , Cinnamates/therapeutic use , DNA Damage , Depsides/therapeutic use , Oxidative Stress/drug effects , Sepsis/drug therapy , Animals , Antioxidants/administration & dosage , Cinnamates/administration & dosage , Comet Assay , Cytokines/blood , Cytokines/metabolism , Depsides/administration & dosage , Kidney/drug effects , Kidney/enzymology , Kidney/immunology , Liver/drug effects , Liver/enzymology , Liver/immunology , Male , Oxidative Stress/genetics , Oxidative Stress/immunology , Rats, Wistar , Sepsis/enzymology , Sepsis/genetics , Sepsis/metabolism , Rosmarinic AcidABSTRACT
Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There is increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is a polyphenolic compound found in the skin of red fruits, such as mulberries and red grapes, and in peanuts. RV has been reported to have an antioxidant, antiproliferative, and anti-inflammatory properties in various models. It has also been found to inhibit the proliferation of a variety of human cancer cell lines, including breast, prostate, colon, pancreatic, and thyroid. This study has been undertaken to assess the role of RV on the sepsis-induced oxidative DNA damage in the lymphocytes of Wistar albino rats by the standard and formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters of tail length, tail intensity, and tail moment were evaluated for the determination of DNA damage. According to the study, the DNA damage was found to be significantly higher in the sepsis-induced rats when compared with the control rats (p < 0.05). The parameters were significantly decreased in the RV-treated sepsis-induced group when compared with the sepsis-induced group. The parameters in the sepsis-induced rats were found to be significantly higher in the Fpg-modified comet assay when compared with the standard comet assay (p < 0.05), and RV treatment decreases the DNA damage in the sepsis-induced rats, suggesting that the oxidative stress is likely to be responsible for DNA damage and RV might have a role in the prevention of sepsis-induced oxidative DNA damage.
