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      The Effect of Thymoquinone on Nuclear Factor Kappa B Levels and Oxidative DNA Damage on Experimental Diabetic Rats

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          Abstract

          Background:

          Thymoquinone (TQ), the basic bioactive phytochemical constituent of seed oil of Nigella sativa, is one of these herbal drugs known for antidiabetic effects. This study was carried out to assess the effects of the possible role of TQ on nuclear factor kappa B (NF-κB) and oxidative DNA damage levels in experimental diabetic rats.

          Materials and Methods:

          Twenty-eight male Wistar Albino rats (200–250 g) were used as experimental subjects. The rats were divided into four groups, including the control, control supplemented with TQ (CT), diabetic (D), and diabetic supplemented with TQ (DT), each containing seven rats. The D and the DT groups were treated with 45 mg/kg streptozotocin (STZ) (intraperitoneal). TQ was administered 30 mg/kg/day for 21 days by oral gavage in the DT and the T groups.

          Results:

          It was determined that glucose, glycosylated hemoglobin (HbA1c) levels and alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase activities were decreased significantly and approached the control group in the DT group after TQ supplement ( P < 0.05). Urea levels were the lowest in CT ( P < 0.05). Oxidative DNA damage (8 hydroxy-2-deoxyguanosine) was increased in both of the diabetic groups (D and DT). The NF-κB levels were the highest in Group D ( P < 0.05).

          Conclusion:

          It was observed that increased glucose and HbA1c levels and the indicators of liver and kidney damages were decreased significantly after TQ supplementation. Oxidative DNA damage and NF-κB levels were increased in the diabetic group, and TQ administration caused a statistically insignificant reduction.

          SUMMARY

          • In this study, the effects of thymoquinone (TQ), the basic bioactive phytochemical constituent of seed oil of Nigella sativa, on nuclear factor kappa B (NF-κB), oxidative DNA damage levels, and, some biochemical parameters was invesigated. It was observed that some biochemical parameters (glucose, glycosylated hemoglobin (HbA1c), ALT, AST, GGT) were close to the control group after TQ treatment in diabetic group. Oxidative DNA damage (8 hydroxy 2 deoxyguanosine) and NF-κB were highest levels and TQ implementation caused statistically insignificant decrease, in the diabetic group.

          Abbreviations used: 8-OHdG: 8 hydroxi-2-deoxiguanosin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; HbA1c: Glycosylated hemoglobin; NF-κB: Nuclear factor kappa protein; STZ: Streptozotocin; TQ: Thymoquinone.

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          Most cited references34

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          Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

          Rany Salem (2005)
          A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1- and Th2-mediated inflammatory immune diseases. Ultimately, results emerging from such studies will substantially improve the immunotherapeutic application of TQ in clinical settings.
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            Oxidative damage to DNA in diabetes mellitus.

            Increased production of reactive oxygen species (ROS) and lipid peroxidation may contribute to vascular complications in diabetes. to test whether DNA is also oxidatively damaged in diabetes, we measured 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative damage of DNA, in mononuclear cells. For this laboratory-based study, 12 patients with insulin-dependent diabetes mellitus (IDDM) and 15 patients with non-insulin-dependent diabetes mellitus (NIDDM) were matched by age with ten healthy volunteers each. DNA was extracted from mononuclear cells from whole blood. 8-OHdG was assayed by high-pressure liquid chromatography, and ROS were assayed by chemiluminescence. IDDM and NIDDM patients had significantly higher median concentrations (p , 0.001, U test) of 8-OHdG in their mononuclear cells than their corresponding controls (in fmol/micrograms DNA): 128.2 (interquartile range 96.0-223.2) and 95.2 (64.0-133.5) vs 28.2 (21.7-43.4) and 21.9 (18.0-24.4), respectively. ROS generation by mononuclear cells was also significantly greater (p < 0.01) in diabetic patients than in their controls (in mV): 238.0 (107.0-243.0) and 101.3 (66.0-134.0) vs 69.5 (49.8-91.9) and 56.0 (38.8-62.5), respectively. IDDM and NIDDM patients showed greater oxidative damage to DNA, with increased generation of ROS, than controls. Such changes might contribute to accelerated aging and atherogenesis in diabetes and to the microangiopathic complications of the disease.
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              Oxidative DNA damage and obesity in type 2 diabetes mellitus.

              This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls. Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds. Serum 8-hydroxy 2'-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml). Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.
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                Author and article information

                Journal
                Pharmacogn Mag
                Pharmacogn Mag
                PM
                Pharmacognosy Magazine
                Medknow Publications & Media Pvt Ltd (India )
                0973-1296
                0976-4062
                October 2017
                11 October 2017
                : 13
                : Suppl 3
                : S458-S461
                Affiliations
                [1]Department of Chemistry, Faculty of Science, Yuzuncu Yil University, Van, Turkey
                [1 ]Department of Biochemistry, Yuzuncu Yil University, Faculty of Veterinary Medicine, Van, Turkey
                Author notes
                Correspondence: Dr. Semiha Dede, Department of Biochemistry, Yuzuncu Yil University, Faculty of Veterinary Medicine, Van, Turkey. E-mail: sdede@ 123456yyu.edu.tr
                Article
                PM-13-458
                10.4103/pm.pm_134_17
                5669082
                29142399
                4d5f50c9-bbe9-4de0-a856-b9ae7ea54ec7
                Copyright: © 2017 Pharmacognosy Magazine

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 10 April 2017
                : 17 May 2017
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                dna damage,experimental diabetes,nuclear factor-kappa b,streptozotocin,thymoquinone

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