Drosophila melanogaster Modelinde Maleik Asit ve Vanilik Asitin Bakır Toksisitesi Üzerine Etkilerinin Araştırılması

Abstract

Bakır, tüm canlı organizmaların biyolojik fonksiyonlarının sürdürülmesi için gerekli olan bir metaldir. Bakır, düşük konsantrasyonlarda hücresel metabolizmanın sürdürülmesi için gerekli olmasına rağmen, yüksek konsantrasyonlarda ROS oluşumuna neden olduğundan toksik etkilere neden olabilir. Bu çalışmada larva ve yetişkin D. melanogaster'de CuSO4 (1 mM) ile toksisite oluşturuldu. Sinekler daha sonra maleik asit (MA) (2 mg) ve vanilik asit (VA) (2 mg) ile işlendi. Sonuçlar Cu toksisitesinin SOD, CAT, GPX, AChE ve GSH düzeylerinde azalmaya neden olduğunu gösterdi. MDA düzeylerinde önemli bir artış oldu. Ancak MA ve VA tedavisinin SOD, CAT, GPX, AChE ve GSH miktarlarını artırdığı, MDA miktarını ise azalttığı belirlendi. Bu sonuçlar MA ve VA'nın CuSO4'ün neden olduğu ROS ve oksidatif stres üzerinde iyileştirici etkilere sahip olduğunu gösterdi. Sonuç olarak, gelecekteki çalışmalarda metal kaynaklı toksisiteye karşı doğal bileşiklerin farklı biyolojik parametreler üzerindeki etkileri değerlendirilmelidir.

Keywords

• Antioksidan
• Drosophila
• Maleik asit
• Vanilik asit

Investigation of the Effects of Maleic Acid and Vanillic Acid on Copper Toxicity in the Drosophila melanogaster Model

Abstract

Copper is a metal that is necessary for the maintenance of biological functions of all living organisms. Although copper is essential for the maintenance of cellular metabolism at low concentrations, at high concentrations it can cause toxic effects as it causes ROS formation. In this study, toxicity was induced by CuSO4 (1 mM) in larval and adult D. melanogaster. The flies were then treated with maleic acid (MA) (2 mg) and vanillic acid (VA) (2 mg). The results showed that Cu toxicity caused a decrease in SOD, CAT, GPX, AChE and GSH levels. There was a significant increase in MDA levels. However, it was found that treatment with MA and VA increased the amounts of SOD, CAT, GPX, AChE and GSH and decreased the amount of MDA. These results showed that MA and VA had ameliorative effects on ROS and oxidative stress caused by CuSO4. In conclusion, the effects of natural compounds on different biological parameters against metal-induced toxicity should be evaluated in future studies.

Keywords

• Antioxidant
• Drosophila
• Maleic acid
• Vanillic acid

References

1. Everman ER, Macdonald SJ, Kelly JK. The genetic basis of adaptation to copper pollution in Drosophila melanogaster. Frontiers in Genetics. 2023;14.
2. Schlichting D, Sommerfeld C, Müller-Graf C, Selhorst T, Greiner M, Gerofke A, et al. Copper and zinc content in wild game shot with lead or non-lead ammunition – implications for consumer health protection. Plos One. 2017;12(9):e0184946.
3. Gaetke L. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology. 2003;189(1–2):147–163.
4. Halmenschelager PT, da Rocha JBT. Biochemical CuSO4 Toxicity in Drosophila melanogaster Depends on Sex and Developmental Stage of Exposure. Biological Trace Element Research. 2019;189(2):574–585.
5. Tapiero H, Townsend DM, Tew KD. Trace elements in human physiology and pathology. Copper. Biomedicine & Pharmacotherapy. 2003;57(9):386–398.
6. Oe S, Miyagawa K, Honma Y, Harada M. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease. Experimental Cell Research. 2016;347(1):192–200.
7. Uriu-Adams JY, Keen CL. Copper, oxidative stress, and human health. Molecular Aspects of Medicine. 2005;26(4–5):268–298.
8. Barber RG, Grenier ZA, Burkhead JL. Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease. Biomedicines. 2021;9(3):316.

9. Liu H, Guo H, Jian Z, Cui H, Fang J, Zuo Z, et al. Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver. Oxidative Medicine and Cellular Longevity. 2020;2020:1–20.
10. Jasemi SV, Khazaei H, Morovati MR, Joshi T, Aneva IY, Farzaei MH, et al. Phytochemicals as treatment for allergic asthma: Therapeutic effects and mechanisms of action. Phytomedicine. 2024;122:155149.
11. Mahmud J Al, Hasanuzzaman M, Nahar K, Rahman A, Hossain MdS, Fujita M. Maleic acid assisted improvement of metal chelation and antioxidant metabolism confers chromium tolerance in Brassica juncea L. Ecotoxicology and Environmental Safety. 2017;144:216–226.
12. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry. 1968;25:192–205.
13. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979;95(2):351–358.
14. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1–2):248–254.
15. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.
16. Aebi H. [13] Catalase in vitro. In: Methods in enzymology. 1984: 121–126.
17. Beutler E. Red Cell Metabolism Manual of Biochemical Methods. 1971. London, UK: Academic Press.
18. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7(2):88–95.
19. Pujol J, Fenoll R, Macià D, Martínez-Vilavella G, Alvarez-Pedrerol M, Rivas I, et al. Airborne copper exposure in school environments associated with poorer motor performance and altered basal ganglia. Brain and behavior. 2016;6(6):e00467.
20. Mitra S, Keswani T, Dey M, Bhattacharya S, Sarkar S, Goswami S, et al. Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus. Toxicology. 2012;293(1–3):78–88.
21. Bellion M, Courbot M, Jacob C, Blaudez D, Chalot M. Extracellular and cellular mechanisms sustaining metal tolerance in ectomycorrhizal fungi. FEMS Microbiology Letters. 2006;254(2):173–181.
22. Cavalcanti Luna MA, Vieira ER, Okada K, Campos-Takaki GM, Nascimento AE do. Copper-induced adaptation, oxidative stress and its tolerance in Aspergillus niger UCP1261. Electronic Journal of Biotechnology. 2015;18(6):418–427.
23. Kumar S, Prahalathan P, Raja B. Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study. Redox Report. 2011;16(5):208–215.
24. Okado-Matsumoto A, Fridovich I. Subcellular Distribution of Superoxide Dismutases (SOD) in Rat Liver. Journal of Biological Chemistry. 2001;276(42):38388–38393.
25. Budiyanti DS, Moeller ME, Thit A. Influence of copper treatment on bioaccumulation, survival, behavior, and fecundity in the fruit fly Drosophila melanogaster: Toxicity of copper oxide nanoparticles differ from dissolved copper. Environmental Toxicology and Pharmacology. 2022;92:103852.
26. Igharo OG, Ebaluegbeıfoh LO, Aıkpıtanyı-Iduıtua GA, Oshılonyah HU, Momodu IB. Resveratrol protects against copper and iron toxicity in Drosophila melanogaster. Universa Medicina. 2023;42(1):29–40.
27. Yeon J, Park AR, Nguyen HTT, Gwak H, Kim J, Sang MK, et al. Inhibition of Oomycetes by the Mixture of Maleic Acid and Copper Sulfate. Plant Disease. 2022;106(3):960–965.
28. Wu C, Chen H-C, Chen S-T, Chiang S-Y, Wu K-Y. Elevation in and persistence of multiple urinary biomarkers indicative of oxidative DNA stress and inflammation: Toxicological implications of maleic acid consumption using a rat model. PLOS ONE. 2017;12(10):e0183675.
29. Zhang SS, Noordin MM, Rahman SO, Haron J. Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats. Veterinary and human toxicology. 2000;42(5):261–4.
30. Toraman E, Budak B, Bayram C, Sezen S, Mokhtare B, Hacımüftüoğlu A. Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue. Chemico-Biological Interactions. 2024;387:110793.