Zebra Balığı Embriyolarında Nörotoksin Maruziyetine Karşı Oluşan Yanıta Düşük Doz X-ışınının Etkileri

Abstract

Amaç: Diş hekimliğinde tanı amaçlı görüntüleme yöntemleri sıklıkla kullanılmaktadır. Dijital görüntülemede kullanılan X-ışını dozları düşük olmakla birlikte, tekrarlanan maruziyetler sağlık açısından risk oluşturmaktadır. 1-metil-4-fenil-1,2,3,6-tetrahidropiridin (MPTP) nörotoksini, oksidatif stres aracılığıyla dopaminerjik nöron kaybına neden olur. Bu çalışmanın hipotezi düşük doz X-ışınının (DDXI), MPTP maruziyetindeki zebra balığı embriyolarında oksidan–antioksidan yanıtta değişikliğe neden olabileceğidir. Gereç ve Yöntemler: Zebra balığı embriyoları kontrol, MPTP, DDXI ve DDXI+MPTP gruplarına ayrılmıştır. Maruziyet gruplarında dental X-ışını cihazı (0,08 saniye) ve 400 µM MPTP kullanılmıştır. Gelişimsel parametreler fertilizasyon sonrası 72. saate (hpf) kadar izlenmiştir. 72 hpf’de lipid peroksidasyonu (LPO), nitrik oksit (NO) seviyeleriyle, süperoksit dismutaz (SOD) ve glutatyon S-transferaz (GST) aktiviteleri ölçülmüştür. Bulgular: SOD, GST aktiviteleri ile LPO ve NO seviyeleri tüm maruziyet gruplarında anlamlı şekilde artmıştır. Özellikle DDXI +MPTP maruziyetinde, yalnızca MPTP maruziyetine kıyasla LPO seviyeleri azalmış; SOD ve GST aktiviteleri ise tek başına DDXI ve MPTP gruplarına göre anlamlı derecede yüksek izlenmiştir. Ayrıca DDXI maruziyetinde perikardiyal ödem ve skolyoz gibi gelişimsel anomaliler gözlenmiştir. Sonuç: DDXI+MPTP maruziyeti zebra balığı embriyolarında oksidan–antioksidan dengede bozukluğa neden olmuştur. DDXI’nın etkileri çok yönlüdür ve MPTP gibi diğer stres faktörleri ile etkileşimini daha iyi değerlendirmek için ek çalışmalara ihtiyaç vardır.

Keywords

• Zebra balığı
• Radyasyon
• MPTP
• Oksidatif stres.

Low-dose X-ray Radiation Alters the Response to Neurotoxin Exposure in Zebrafish Embryos

Abstract

Objective: Dental diagnostic imaging is widely used in dentistry. Although X-ray radiation doses in modern digital dental imaging are low, repeated exposures increase the health risks. The neurotoxin 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) specifically impairs dopaminergic neurons by inducing oxidative stress. We hypothesized that low-dose X-ray radiation (LDXR) exposure may modulate oxidant–antioxidant responses in MPTP-exposed embryos. Materials and Methods: Zebrafish embryos were categorized as the control, MPTP, LDXR, and LDXR+MPTP groups. Treatments were performed using an X-ray device for dental purposes and 400 µM MPTP. Devel opmental parameters were monitored until 72 h post fertilization (hpf). Biochemical parameters related to the oxidant and antioxidant status were investigated at 72 hpf. Results: Superoxide dismutase (SOD), glutathione-S transferase (GST) activities, lipid peroxidation (LPO), and nitric oxide (NO) levels were significantly elevated in all exposure groups. Notably, LDXR+MPTP exposure reduced LPO levels compared with MPTP exposure, while SOD and GST were significantly higher than those in the LDXR and MPTP exposed groups. In addition, LDXR exposure induced developmental abnormalities, including pericardial edema and scoliosis. Conclusion: LDXR+MPTP exposure interrupted the oxidant-antioxidant equilibrium in zebrafish embryos. Overall, the effects of LDXR are multifaceted, and additional studies are needed to better comprehend its interactions with other stressors such as MPTP

Keywords

• Zebrafish
• Radiation
• MPTP
• Oxidative stress.

References

1. 1. Hwang SY, Choi ES, Kim YS, Gim BE, Ha M, Kim, HY. Health effects from exposure to dental diagnostic X-ray. Environ Health Toxicol 2018; 33(4): e2018017.
2. 2. Lee EG, Jang GW, Lee KH, Kweon DC. Guidelines for radiation protection in dental radiographic examinations: a questionnaire-based summary. Radiat Eff Defect S 2020; 176(5-6): 397-411.
3. 3. Bergonié J, Tribondeau L. Interpretation of some results from radiotherapy and an attempt to determine a rational treatment technique. 1906. Yale J Biol Med 2003; 76(4-6): 181-2.
4. 4. Hurem S, Martín LM, Brede DA, Skjerve E, Nourizadeh-Lillabadi R, Lind OC, et al. Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression. PloS one 2017; 12(6): e0179259.
5. 5. Xu T, Liu F, He J, Xu P, Qu J, Wang H, et al. Leveraging zebrafish models for advancing radiobiology: Mechanisms, applications, and future prospects in radiation exposure research. Environmental research 2025; 266: 120504.
6. 6. Langston JW. The MPTP Story. J Parkinsons Dis 2017; 7(s1): 11-19.
7. 7. Barnhill LM, Murata H, Bronstein JM. Studying the pathophysiology of Parkinson's Disease using zebrafish. Biomedicines 2020; 8(7): 197.
8. 8. Caliskan S, Emekli-Alturfan E. Zebrafish embryo as an emerging model organism in neurodevelopmental toxicity research. Eur J Biol 2021; 80(2): 179-87.

9. 9. Cansiz D, Ustundag UV, Unal I, Alturfan AA, Emekli-Alturfan E. Morphine attenuates neurotoxic effects of MPTP in zebrafish embryos by regulating oxidant/antioxidant balance and acetylcholinesterase activity. Drug Chem Toxicol 2022; 45(6): 2439-47.
10. 10. Karagoz A, Beler M, Altun BD, Unal I, Cansiz D, Gunduz H, et al. Panoramic dental X-ray exposure leads to oxidative stress, inflammation and apoptosis-mediated developmental defects in zebrafish embryos. J Stomatol Oral Maxillofac Surg 2023; 124(6S): 101661.
11. 11. Kollayan BY, Cansiz D, Beler M, Unal I, Emekli-Alturfan E, Yalcinkaya SE. Effects of low-dose ionizing radiation on the molecular pathways linking neurogenesis and autism spectrum disorders in zebrafish embryos. Drug Chem Toxicol 2024; 47(6): 960-73.
12. 12. Kojima S, Matsuki O, Nomura T, Yamaoka K, Takahashi M, Niki, E. Elevation of antioxidant potency in the brain of mice by low-dose gamma-ray irradiation and its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage. Free Radic Biol Med 1999; 26(3-4): 388-95.
13. 13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
14. 14. Yagi K. Assay for blood plasma or serum. Methods Enzymol 1984; 105: 328-31.
15. 15. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5(1): 62-71.
16. 16. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974; 249(22): 7130-9.
17. 17. Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986; 82(3): 512-20.
18. 18. Hall EJ, Giaccia AJ. Radiobiology for the radiologist. 8th ed. Philadelphia: Wolters Kluwer; 2019.
19. 19. Kochanova D, Gulati S, Durdik M, Jakl L, Kosik P, Skorvaga M et al. Effects of low-dose ionizing radiation on genomic instability in interventional radiology workers. Sci Rep 2023; 13(1): 15525.
20. 20. Narasimhamurthy RK, Venkidesh BS, Dsouz HS, Joshi MB, Murali TS, Kabekkodu SB, et al. Low-dose radiation and malathion co-exposure instigates long-term neurological sequelae and synergistic disruption of lipid homeostasis and energy metabolism in the hippocampus. Sci Rep 2025; 15: 32961.
21. 21. Si J, Zhou R, Zhao B, Xie Y, Gan L, Zhang J, et al. Effects of ionizing radiation and HLY78 on the zebrafish embryonic developmental toxicity. Toxicology 2019; 411: 143-53.
22. 22. Hatjikondi O, Ravazoula P, Kardamakis D, Dimopoulos J, Papaioannou S. In vivo experimental evidence that the nitric oxide pathway is involved in the X-ray induced antiangiogenicity. Br J Cancer 1996; 74(12): 1916-23.
23. 23. Cibuk S, Aras A. Effect of X-ray exposure on oxidative stress in liver and kidney in rats in early life: An experimental study. Kafkas Univ Vet Fak Derg 2025; 31(2): 155-61.
24. 24. Mohammad MK, Mohamed MI, Zakaria AM, Abdul Razak HR, Saad WM. Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates oxidative damage induced by low dose X-ray in mice. Biomed Res Int 2014; 2014: 512834.
25. 25. Nishi M, Takashima H, Oka T, Ohishi N, Yagi, K. Effect of x-ray irradiation on lipid peroxide levels in the rat submandibular gland. J Dent Res 1986; 65(7): 1028-9.
26. 26. Xia XJ, Lian YG, Zhao HY, Xu QL. Curcumin protects from oxidative stress and inhibits ?-synuclein aggregation in MPTP induced parkinsonian mice. Int J Clin Exp Med 2016; 9: 2654-65.
27. 27. Tripodi G, Lombardo M, Kerav S, Aiello G, Baldelli S. Nitric oxide in Parkinson's Disease: The potential role of dietary nitrate in enhancing cognitive and motor health via the nitrate-nitrite-nitric oxide pathway. Nutrients 2025; 17(3): 393.
28. 28. Lau YS, Chew MT, Alqahtani A, Jones B, Hill MA, Nisbet A, Bradley DA. Low dose ıonising radiation-ınduced hormesis: therapeutic ımplications to human health. Appl Sci 2021; 11(19): 8909.
29. 29. Zhou R, Si J, Zhang H, Wang Z, Li J, Zhou X, et al. The effects of x-ray radiation on the eye development of zebrafish. Hum Exp Toxicol 2014; 33(10): 1040-50.
30. 30. Paithankar JG, Raghu SV, Patil RK. Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose. Int J Radiat Biol 2018; 94(6): 576-89