DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin

2019 ◽  
Vol 12 (2) ◽  
pp. 163-172 ◽  
Author(s):  
D. Rašić ◽  
D. Želježić ◽  
N. Kopjar ◽  
D. Kifer ◽  
M. Šegvić Klarić ◽  
...  

The study aimed to check whether ochratoxin A (OTA) and citrinin (CIT) increase DNA damage in the kidney and liver of male Wistar rats (alkaline comet assay), clarify the oxidative nature of DNA damage (hOGG1-modified comet assay), and verify whether resveratrol (RSV) could ameliorate OTA+CIT-induced genotoxicity. Rats were treated orally with OTA (0.125 and 0.250 mg/kg bodyweight (bw)) and CIT (2 mg/kg bw), OTA+CIT combinations and OTA+CIT+RSV (0.250+2+20 mg/kg bw) for 21 days. Both alkaline and hOGG1-modified comet assay showed that DNA damage was more severe in rat kidneys than in liver following mycotoxin treatment. Alkaline comet assay revealed a higher intensity of DNA damage, particularly as measured by tail intensity in the kidneys. Both tail length and tail intensity were OTA dose-dependent, but in combined OTA+CIT treatment these values were similar to CIT alone and lower than in animals treated with single OTA, possibly due to induction of apoptosis. hOGG1-modified comet showed that OTA+CIT evoked greater oxidative DNA damage than single mycotoxins. RSV did not reduce DNA damage measured by alkaline comet assay, but hOGG1-modified comet showed that RSV ameliorated OTA+CIT genotoxicity in the kidneys. Apart from oxidative stress, other mechanisms of DNA damage are involved in OTA and CIT genotoxicity. In rat kidneys RSV can reduce but not overcome oxidative DNA damage induced by combined OTA and CIT.

2013 ◽  
Vol 33 (3) ◽  
pp. 224-229 ◽  
Author(s):  
T Zhang ◽  
Q Zhao ◽  
Y Zhang ◽  
J Ning

The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice. The DNA damage, measured as comet tail length (µm), was determined using the alkaline comet assay. The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model. Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed. The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight. Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm. Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.


Author(s):  
Ahmet Cihat Öner ◽  
Adnan Ayan

This study was aimed to evaluate DNA fragmentation by using Comet assay in naturally infected sheep with Anaplasmosis before and after treatment with the Comet method, which shows DNA damage specifically. In the study, blood samples were collected from 10 Anaplosmosis infected and 10 healthy sheep. The anaplosmosis was diagnosed by clinical signs and symptoms. The infection was confirmed by Giemsa staining. The blood was collected from control group and infected group before and after the treatment, from the vena jugularis with the appropriate method. The DNA fragmentation was checked by using the Comet assay of blood cells. The data were analysed throught ANNOVA one-way. The result showed higher DNA fragmentation in sick animals diagnosed with anaplasmosis; tail length and tail moment values were found to be statistically significantly higher than the control group. When the data obtained after imidocarb (IMD) application were compared with obtained during the disease, a decreased DNA damage and tail moment was determined, however, these values higher than control. In this study, DNA damage and the extent of this damage were investigated by the Comet assay method using a healthy control group before and after treatment in animals with Anaplasmosis. When the findings obtained from the study were evaluated, it was seen that Anaplasma agents caused DNA damage and with the imidocarb application given for treatment, DNA damage was reduced and results close to healthy individuals were obtained.


2010 ◽  
Vol 30 (9) ◽  
pp. 1297-1302
Author(s):  
Tao Zhang ◽  
Jiye Hu ◽  
Yuchao Zhang ◽  
Qianfei Zhao ◽  
Jun Ning

JS-118 is an extensively used insecticide in China. The present study investigated the genotoxic effect of JS-118 on whole blood at 24, 48, 72 and 96 h by using alkaline comet assay. Male Kunming mice were given 6.25, 12.5, 25, 50 and 100 mg/kg BW of JS-118 intraperitoneally. A statistically significant increase in all comet parameters indicating DNA damage was observed at 24 h post-treatment ( p < 0.05). A clear concentration-dependent increase of DNA damage was revealed as evident by the OTM (arbitrary units), tail length (µm) and tail DNA (%). From 48 h post-treatment, a gradual decrease in mean comet parameters was noted. By 96 h of post-treatment, the mean comet tail length reached control levels indicating repair of damaged DNA. This study on mice showed different DNA damage depending on the concentration of JS-118 and the period of treatment. The present study provided further information of the potential risk of the genetic damage caused by JS-118.


2021 ◽  
Vol 14 ◽  
Author(s):  
Necla Benlier ◽  
Nilay Uçar ◽  
Eda Öğüt ◽  
Havva Yeşil Çinkir ◽  
Mustafa Yildirim ◽  
...  

Objective: The present study aims to evaluate the antioxidant effect of beta glucan on oxidative DNA damage by comet assay. Methods: A total of 19 adult females and males diagnosed with stage 3-4 colorectal cancer and a control group of 20 age-matched healthy subjects were enrolled in the study. Blood samples of the participants were analyzed using Comet Assay for the parameters of DNA damage. Results: Significantly increased DNA damage was observed in patients versus control group as indicated by greater values of tail moment, tail percent DNA and tail length. Following incubation with β-glucan, a substantial reduction was found in the aforementioned parameters of DNA damage. Comet assay revealed significant levels of endogenous DNA damage in patients as shown by remarkable increases in the tail moment, the percentage of DNA in the tail and the tail length values, in comparison with the control group. Following treatment of fresh whole blood with β-glucan incubation, DNA damages were significantly reduced but lower values were observed after β-glucan incubation in the patient group versus control group. Conclusion: β-Glucan was found to reduce DNA damage substantially in colorectal cancer patients and show antimutagenic effects. Our results suggested that dietary β-glucan intake might be important in the genesis of colorectal cancer tumors.


2014 ◽  
Vol 395 (12) ◽  
pp. 1461-1466 ◽  
Author(s):  
Mohamed Badr ◽  
Christian Kopp ◽  
Sandra Theison ◽  
Jennifer Meyer ◽  
Wolfgang E. Trommer

Abstract An immunotoxin composed of gelonin, a basic ribosome-inactivating protein, type I of 30 kDa, isolated from the seeds of the Indian plant Gelonium multiflorum and methotrexate (MTX) has been studied as a potential tool of gelonin delivery into the cytoplasm of MTX-responsive cells. On the average, about five molecules of methotrexate were chemically coupled to gelonin via an N-hydroxysuccinimide ester of the drug. The MTX-gelonin conjugate was able to reduce the viability of MCF-7 cells in a dose-dependent manner with ID50 of 10 nm, whereas gelonin or MTX alone showed none or very little effects. Besides its ribosome-inactivating activity, which is about ten-fold lower in an in vitro translation assay (IC50 of 50.5 ng/ml as compared to 4.6 ng/ml), the conjugate also significantly induced direct and oxidative DNA damage as shown by the alkaline comet assay. Hence, MTX-gelonin conjugates are promising candidates for the treatment of MTX-responsive cancers.


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