Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats

Abstract

Background: The increases of free radicals have been proposed to be involved in the pathogenesis of sepsis, which leads to multiple-organ dysfunction syndromes. The uses of antioxidants as a complementary tool in the medical care of oxidative stress-related diseases have attracted attention of researchers. Resveratrol (RV) has suggested being antioxidant, anti-proliferative, and anti-inflammatory effects in various experimental models and clinical settings. Aims: This study was undertaken to evaluate the protective effects of RV on oxidative DNA damage induced by sepsis in the liver and kidney tissues of Wistar albino rats. Study Design: Animal experimentation. Methods: Four experimental groups consisting of eight animals for each was created using a total of thirty-two male Wistar albino rats. Sham group was given 0.5 mL of saline intra-peritoneal (ip) only following laparatomy. Sepsis group was given 0.5 mL saline ip only following the induction of sepsis. RV-treated group was given a dose of 100 mg/kg ip RV in 0.5 mL saline following laparatomy. RV-treated sepsis group was given 100 mg/kg ip RV in 0.5 mL saline following the induction of sepsis. A model of sepsis was created by cecal ligation and puncture technique. In the liver and kidney tissues, oxidative stress parameters (malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX)) and a proinflammatory cytokine (tumor necrosis factor alpha (TNF-alpha)), were evaluated spectrophotometrically and DNA damage was determined by the alkaline single cell gel electrophoresis (comet assay) technique using formamidopyrimidine DNA glycosylase protein. Results: In the RV-treated sepsis group, the levels of MDA and TNF-alpha were lower and GSH levels, SOD and GPX activities were higher than in the septic rats (p<0.05). RV treatment significantly reduced the sepsis-induced oxidative DNA damage in the liver and kidney cells (p<0.05). Conclusion: It is suggested that RV treatment might reduce the sepsis-induced oxidative DNA damages in sepsis-related diseases; however, there is a need for more studies to clear up the protective mechanisms of RV against sepsis.

Keywords

• Resveratrol, sepsis, tumor necrosis factor alpha, oxidative stress, DNA damage, alkaline single cell gel electrophoresis

Kaynakça

1. 1. Andrades M, Ritter C, Moreira JDF, Dal-Pizzol F. Oxidative parameters differences during non-lethal and lethal sepsis development. J Surg Res 2005;125:68-72. [CrossRef]
2. 2. Andrades ME, Ritter C, Dal-Pizzol F. The role of free radicals in sepsis development. Front Biosci 2009;1:277-87.
3. 3. Bishayee A, Barnes KF, Bhatia D, Darvesh AS, Carroll RT. Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis. Cancer Prev Res (Phila) 2010;3:753-63. [CrossRef]
4. 4. Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishoda S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 2004;24:2783-840.
5. 5. Eybl V, Kotyzová D, Cerná P, Koutensky J. Effect of melatonin, curcumin, quercetin, and resveratrol on acute ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative damage in rats. Hum Exp Toxicol 2008;27:347-53. [CrossRef]
6. 6. Bujanda L, Garcı´a-Barcina M, Gutie´rrez-de Juan V, Bidaurrazaga J, de Luco MF, Gutie´rrez-Stampa M, et al. Effect of resveratrol on alcohol-induced mortality and liver lesions in mice. BMC Gastroenterol 2006;6:35. [CrossRef]
7. 7. Sener G, Toklu HZ, Sehirli AO, Velioğlu-Öğünç¸ A, Cetinel S, Gedik N. Protective effects of resveratrol against acetaminophen-induced toxicity in mice. Hepatol Res 2006;35:62-8. [CrossRef]
8. 8. Collins AR, Duthie SJ, Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 1993;14:1733-5. [CrossRef]

9. 9. Aydin S, Bacanli M, Taner G, Şahin T, Başaran AA, Başaran N. Protective effects of resveratrol on sepsis-induced DNA damage in the lymphocytes of rats. Hum Exp Toxicol 2013;32:1048-57. [CrossRef]
10. 10. Parker SJ, Watkins PE. Experimental models of gram negative sepsis. Br J Surg 2001;88:22-30. [CrossRef]
11. 11. Ritter C, Andrades M, Frota ML, Pinho R, Polydoro M, Klamt F, et al. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 2003;29:1782- 9. [CrossRef]
12. 12. Della-Morte D, Dave KR, DeFazio RA, Bao YC, Raval AP, Perez-Pinzon MA. Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience 2009;159:993-1002. [CrossRef]
13. 13. Taner G, Aydin S, Bacanli M, Sarıgöl Z, Sahin T, Basaran AA, et al. Modulating Effects of Pycnogenol® on Oxidative Stress and DNA Damage Induced by Sepsis in Rats. Phytother Res 2014;28:1692-700. [CrossRef]
14. 14. Bacanlı M, Aydın S, Taner G, Göktaş HG, Sahin T, Başaran AA, et al. The protective role of ferulic acid on sepsis-induced oxidative damage in Wistar albino rats. Environ Toxicol Pharmacol 2014:38:774-82. [CrossRef]