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Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats

Hatice G. Goktas1, 2*, Merve Bacanli1, Sevtap Aydin1, Gokce Taner3, Tolga Sahin4, Arif Ahmet Başaran5 and Nursen Basaran1
  • 1 Hacettepe University Faculty of Pharmacy, Department of Toxicology, Türkiye
  • 2 Cukurova University Faculty of Pharmacy, Department of Toxicology, Türkiye
  • 3 Gazi University, Faculty of Science, Biology, Türkiye
  • 4 Hacettepe University Faculty of Kastamonu Medicine, Surgery, Türkiye
  • 5 Hacettepe University Faculty of Pharmacy, Pharmacognosy, Türkiye

Sepsis is an imbalance between pro and anti-inflammatory responses. Sepsis induced multiple organ failure that is associated with mortality is characterized by liver, renal, cardiovascular and pulmonary dysfunction and reactive oxygen species (ROS) are believed to be involved in the development of sepsis. Plant polyphenols may act as antioxidants by different mechanisms such as free radical scavenging, metal chelation and protein binding. Data indicates possible beneficial effects of plant derived phenolic compounds against sepsis. Rosmarinic acid (RA) (α-O-caffeoyl-3,4-dihydroxyphenyllactic acid) is a phenolic compound commonly found in various plants such as Rosmarinus officinalis (rosemary), Origanum vulgare (oregano), Thymus vulgaris (thyme), Mentha spicata (spearmint), Perilla frutescens (perilla), Ocimum basilicum (sweet basil) and several other medicinal plants. It has been shown that RA has many biological activities including antioxidant, anti-inflammatory, antiallergic, anticancer and actimicrobial and is widely used in cosmetic and food industry. In the present study, we aimed to determine the protective effects of RA against the oxidative DNA damage induced by sepsis in Wistar albino rats. The rats were divided into four groups; sham, sepsis induced, RA-treated, RA treated and sepsis induced groups. Wistar rats were subjected to sepsis by cecal ligation puncture. The liver tissues were carefully dissected from their attachments and totally excised. The concentrations of the hepatic tissue cells were adjusted to approximately 2 x 106 cells/ml. Standard and formamidopyrimidine-DNA glycosylase (Fpg) modified comet assay described by Singh et al were used. There were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated groups (p>0.05). The DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p<0.05). RA treatment in the sepsis-induced group was found to decrease the DNA damage significantly (p<0.05). Similarly in the Fpg-modified comet assay, there were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated group (p>0.05), and the DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p<0.05). RA treatment in the sepsis-induced group was found to decrease the DNA damage significantly (p<0.05). In conclusion, RA might have a role in the prevention of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing DNA repair capacity of the animals.

References

1. Collins AR, Duthie SJ and Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis. 1993; 14: 1733-5.
2. Domitrovic R, Skoda M, Vasiljev Marchesi V, Cvijanovic O, Pernjak Pugel E and Stefan MB. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol 2013; 51: 370-8.
3. Ritter C, Andrades M, Frota Jr MLC, et al. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intens Care Med 2003; 29: 1782-9.
4. Singh NP, McCoy MT, Tice RR and Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988; 175: 184-91.

Keywords: Rosmarinic acid, Sepsis, Comet Assay, DNA Damage, plant phenolics

Conference: ICAW 2015 - 11th International Comet Assay Workshop, Antwerpen, Belgium, 1 Sep - 4 Sep, 2015.

Presentation Type: Poster Discussion

Topic: Genotoxicity testing of chemicals and nanomaterials

Citation: Goktas HG, Bacanli M, Aydin S, Taner G, Sahin T, Başaran A and Basaran N (2015). Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats. Front. Genet. Conference Abstract: ICAW 2015 - 11th International Comet Assay Workshop. doi: 10.3389/conf.fgene.2015.01.00020

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Received: 02 Jun 2015; Published Online: 23 Jun 2015.

* Correspondence: Miss. Hatice G Goktas, Hacettepe University Faculty of Pharmacy, Department of Toxicology, Ankara, 06110, Türkiye, haticegulgoktas@gmail.com