In vivo protective efficacy of astaxanthin against ionizing radiation-induced DNA damage.

Astaxanthin, a carotenoid pigment, is believed to be effective in the repair of DNA damage. Our study evaluates the effect of astaxanthin on DNA damage in rats exposed to whole-body radiotherapy using the comet assay. Thirty-two male rats were randomly divided into four groups (control, ionizing radiation, astaxanthin, and radiation+astaxanthin). The radiation and radiation+astaxanthin groups were exposed to X-rays at a dose of 8 gray (0.62 gray/min). Astaxanthin was administered at 4 mg/kg by gavage for 7 days starting from irradiation. The %TailDNA parameter was chosen as an indicator of DNA damage and the results were compared using one-way ANOVA. %TailDNA was 3.24 ± 3.12 in the control group, 2.85 ± 2.73 in the astaxanthin group, 4.11 ± 7.90 in the radiation group, and 3.59 ± 4.05 in the radiation+astaxanthin group. There was a significant increase in DNA damage in the radiation group, compared with the control and astaxanthin groups (p < .001). DNA damage was reduced in the radiation+astaxanthin group compared with the radiation group (p < .05). Although this decrease did not reduce damage to the level of the control group, it was significant. The decrease in radiation-induced DNA damage by astaxanthin administration in our study supports the hypothesis that astaxanthin is a promising agent for against/reducing DNA damage.

Genotoxicity of thiacloprid in zebrafish liver.

Thiacloprid (TH), one of the most widely used pesticides in the world, might cause toxic effects like DNA damage in humans and animals due to their frequent use. Accordingly, this study investigated TH's potential DNA-damaging effects on zebrafish liver via alkaline comet assay. Two treatment groups of ten zebrafish each were exposed to TH at two different concentrations, 1.64 and 0.82 mg/L, for 21 days and compared with an untreated control group. After exposure, the fishes' liver tissues were excised, and an alkaline comet assay was performed. Two slides per sample and 50 cells per slide were assessed with a visual evaluation program. The average DNA Damage values of the control, 0.82 mg/L TH, and 1.64 mg/L TH groups were 4.37 ± 5.12, 8.51 ± 8.54, and 9.30 ± 9.99, respectively. Both TH treatment groups had statistically significantly more DNA damage than the control group (p < 0.001). When comparing the TH treatment groups alone, the 1.64 mg/L dose group featured greater damage than the 0.82 mg/L dose group (p < 0.05). TH therefore causes significant DNA damage to the liver in a dose-dependent manner, revealing it to be a genotoxic agent that should be further investigated.

Lymphocyte DNA damage in sepsis and septic-shock intensive-care patients: Damage is greater in non-intubated patients.

Sepsis is an excessive host response to infection; septic shock is a more severe clinical condition. We studied 43 sepsis patients, 32 septic-shock patients, and a group of healthy controls. The patients' Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) 2 score were much higher in the septic-shock group than in the sepsis group. We used the comet assay to measure lymphocyte DNA damage; the damage scores were significantly higher in both the sepsis and the septic-shock groups compared to the healthy controls. There was no statistically significant difference between the sepsis and septic-shock groups. We also compared DNA damage levels of intubated vs. non-intubated patients. DNA damage was significantly higher in non-intubated patients compared to intubated patients, for both the sepsis and the septic-shock groups. Early intubation may be beneficial in non-intubated patients who have high levels of DNA damage.

DNA damage effect of cyprodinil and thiacloprid in adult zebrafish gills.

Cyprodinil and thiacloprid are two of the most commonly used pesticides in Turkey. It is more likely to reach humans or animals due to their widespread use. This study aims to investigate whether there is a DNA damage risk due to cyprodinil and thiacloprid exposure. Zebrafish, which is used as a model organism in health and environmental research, and comet assay were chosen to demonstrate this damage. Ten zebrafish per group were exposed to 2 different concentrations for each pesticides (0.31 and 0.155 mg/L for cyprodinil and 1.64 and 0.82 mg/L for thiacloprid) for 21 days. After, gills were excised and comet assay was performed. Photos of an average of 50 cells per slide were taken and were analyzed with visual evaluation program. DNA damage was found to be increased in the 0.31 mg/L cyprodinil, 0.82 mg/L thiacloprid, and 1.64 mg/L thiacloprid treatment groups when compared to the control group (p < 0.001). Average tail DNA percentage parameter values were 9.45 ± 0.51, 10.30 ± 0.34, 11.17 ± 0.33, and 2.47 ± 0.06 respectively. Cyprodinil and thiacloprid were identified as genotoxic agents that should be investigated further.

Ochratoxin A causes cell cycle arrest in G1 and G1/S phases through p53 in HK-2 cells.

Ochratoxin A (OTA) is a toxic metabolite produced by Aspergillus and Penicillium fungus. OTA found in the human and animal tissues can contaminate many foods that we daily consume in our lives. It accumulates especially in kidney. Although OTA is known to cause cell cycle arrest, the molecular mechanisms underlying this effect have not been fully understood, yet. We aimed to investigate the molecular details of OTA induced inhibitory response in G1 - G1/S phase of cell cycle and also the regulatory role of p53 in OTA mediated cell cycle arrest in human proximal tubule epithelial cells, HK-2. For this purpose, Cyclin E1 and Cyclin D1 mRNA expressions and Cyclin D1, Cdk4 and Cdk2 protein expressions were evaluated in HK-2 cells transfected with either 50 nM control siRNA or p53 siRNA for 72 h in the absence or presence of OTA using RT-PCR and Western blot analyses, respectively. Our findings showed that mRNA expressions of Cyclin D1 and Cyclin E1 and protein expressions of Cyclin D1, Cdk4 and Cdk2 were inhibited in HK-2 cells treated with two different doses of OTA, 10 µM and 25 µM, for 24 h. However, the downregulation of p53 led to enhance OTA-mediated increase in mRNA expressions of Cyclin D1 and Cyclin E1 and protein expressions of Cyclin D1, Cdk4 and Cdk2 compared to control siRNA transfected HK-2 cells. Our findings strongly suggest that the cell cycle arresting effect of OTA also performs via a p53 mediated mechanism besides other possible mechanisms.