Study The Effects of Curcumın and Naringenın on Liver Damage Caused by Copper Nanoparticles

Abstract

Introduction: The increase in the frequency of use of copper nanoparticles (CuNP) results in an increased exposure of humans to this substance. Curcuma longa L. and Naringenin consumption reduces the risk of developing cancer types and helps protective biological effects in humans.
Aim: In our study, the possible effects of different doses of curcumin and naringenin on the application of copper nanoparticles, oxidative stress and inflammation were investigated.
Methods: In this study, 42 rats were divided into 6 groups. One of the groups was the control group, while the other groups were administered different doses of curcumin and naringenin substances as well as CuNP. At the end of the study, after the liver tissue was isolated and Superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH), Malondialdehyde (MDA) activities and inflammation markers (IL-1α, IL-1β) were investigated.
Result: As a result, it was found that copper nanoparticles increased oxidative stress and decreased antioxidant enzyme activities, while curcumin and naringenin decreased oxidative stress and increased antioxidant enzyme levels. When the IL-1α parameter in liver tissue was examined, the level of IL-1α decreased, this decrease was not statistically significant. The IL-1β parameter showed a statistically significant increase in the CuNP group compared to the control group (p<0.05). IL-1β level was decreased in different doses of curcumin and naringenin groups compared to CuNP group (p<0.05).
Conclusion: It can be thought that curcumin and naringenine can be used for the protection and treatment against detrimental effects that may occur in case of exposure to copper nanoparticles in humans.

Keywords

• Copper nanoparticles
• liver
• oxidative stress
• curcumine
• naringenin

Kurkumin ve Naringenin’in Bakır Nanopartikülleri ile Oluşturulmuş Karaciğer Hasarı Üzerine Etkilerinin İncelenmesi

Abstract

Giriş: Bakır nanopartiküllerinin (CuNP) günümüzde kullanım sıklığındaki artış insanların bu maddeye olan maruziyetin artması ile sonuçlanmaktadır. Curcuma longa L. ve Naringenin kanser türlerinin oluşma riskinin azaltmakta ve insanlarda koruyucu biyolojik etkilere yardımcı olmaktadır.
Amaç: Çalışmamızda, bakır nanopartiküller ile oluşturulmuş oksidatif strese karşı kurkumin ve naringeninin olası koruyucu etkileri incelenmiştir.
Yöntem: Çalışmamızda 42 rat 6 gruba ayrılmıştır. Gruplardan biri kontrol grubu iken, diğer gruplara farklı dozlarda kurkumin ve naringenin maddeleri ile CuNP uygulanmıştır. Çalışma sonunda karaciğer dokusu izole edildi ve Süperoksit Dismutaz (SOD), Katalaz (KAT) aktiviteleri, Glutatyon (GSH), Malondialdehit (MDA) düzeyleri ve inflamasyon belirteçleri (IL-1α, IL-1β) araştırılmıştır.
Bulgular: Elde edilen bulgular sonucunda, bakır nanopartiküllerin oksidatif stresi arttırdığı ve antioksidan enzim seviyelerinde düşüşe sebep olduğu; kurkumin ve naringeninin ise oksidatif stresi azalttığı ve antioksidan enzim seviyelerini arttırdığı saptanmıştır. Karaciğer dokusunda IL-1α parametresi incelendiğinde, kontrol grubu ve farklı dozlarda kurkumin ve naringenin CuNP ile karşılaştırıldığında, IL-1α düzeyinde azalma saptanmıştır. Bu düşüş istatistiksel olarak anlamlı değildi. IL-1β parametresi, kontrol grubuna kıyasla CuNP grubunda istatistiksel olarak anlamlı bir artış gösterdi (p<0.05). IL-1β düzeyi incelendiğinde diğer gruplara kıyasla CuNP grubunda artma saptanmıştır.
Sonuç: İnsanların bakır nanopartiküllere maruz kalması durumunda oluşabilecek zararlı etkilerden korunma ve tedavi için kurkumin ve naringenin kullanılabileceği düşünülebilir.

Keywords

• Bakır nanopartikül
• karaciğer
• oksidatif stres
• kurkumin
• naringenin

References

1. 1. Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arabian journal of chemistry 2019;12(7):908-931.
2. 2. Masciangioli T, Zhang WX. Peer reviewed: environmental technologies at the nanoscale. Environmental Science &Technology 2003;37(5):102A–108A.
3. 3. Handy RD, et al. The ecotoxicology and chemistry of manufactured nanoparticles. Ecotoxicology 2008;17(4):287-314.
4. 4. Parada J, et al. The nanotechnology among US: are metal and metal oxides nanoparticles a nano or mega risk for soil microbial communities? Critical reviews in biotechnology 2019;39(2):157-172.
5. 5. Andra S, et al. Phytosynthesized metal oxide nanoparticles for pharmaceutical applications. Naunyn-Schmiedeberg's archives of pharmacology 2019;392(7):755-771.
6. 6. Yah CS, Iyuke SE, Simate GS. A review of nanoparticles toxicity and their routes of exposures. Iranian Journal of Pharmaceutical Sciences 2012;8(1):299-314.
7. 7. Oberdörster G, Stone V, Donaldson K. Toxicology of nanoparticles: a historical perspective. Nanotoxicology 2007;1(1):2-25.
8. 8. Almeida JPM, et al. In vivo biodistribution of nanoparticles. Nanomedicine 2011;6(5):815-835.

9. 9. Jones CF, Grainger DW. In vitro assessments of nanomaterial toxicity. Advanced drug delivery reviews 2009;61(6):438-456.
10. 10. Landsiedel R, et al. Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations—many questions, some answers. Mutation Research/Reviews in Mutation Research 2009;681(2-3):241-258.
11. 11. Karlsson HL, et al. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chemical research in toxicology 2008;21(9):1726-1732.
12. 12. Karlsson HL, et al. Size-dependent toxicity of metal oxide particles—a comparison between nano-and micrometer size. Toxicology letters 2009;188(2):112-118.
13. 13. Ravindran PN, Nirmal-Babu K, Sivaraman K. Turmeric: The golden spice of life. Turmeric: The Genus Curcuma. FL, USA: CRC Press, Boca Raton 2007.
14. 14. Mbaveng AT, Qiaoli Z, Victor K. In Toxicological Survey of African Medicinal Plants. Elsevier 2014;577-609.
15. 15. Zobeiri M, et al. Naringenin and its nano-formulations for fatty liver: cellular modes of action and clinical perspective. Current pharmaceutical biotechnology 2018;19(3):196-205.
16. 16. Salehi B, et al. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals 2019;12(1):11.
17. 17. Lowry OH, et al. Protein Measurement wıth The Folin Phenol Reagent. Journal of Biological Chemistry 1951;193(1):265-275.
18. 18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry 1979;95(2):351-358.
19. 19. Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinical chemistry 1988;34(3):497-500.
20. 20. Aebi H. Catalase in vitro. Methods in enzymology 1984;105:121-126.
21. 21. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry 1968;25(1):192-205.
22. 22. Lee IC, et al. Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats. International journal of nanomedicine 2016;11:2883.
23. 23. Pettibone JM, et al. Inflammatory response of mice following inhalation exposure to iron and copper nanoparticles. Nanotoxicology 2008;2(4):189-204.
24. 24. Kim JS, et al. Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model. Particle and fibre toxicology 2011;8(1):1-14.
25. 25. Madsen E, Gitlin JD. Copper and iron disorders of the brain. Annu. Rev. Neurosci 2007;30(1):317-337.
26. 26. Sharma RP, et al. Fumonisin toxicity in a transgenic mouse model lacking the mdr1a/1b P-glycoprotein genes. Environmental toxicology and pharmacology 2000;8(3):173-182.
27. 27. Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental health perspectives 2005;113(7):823-839.
28. 28. Meng H, et al. Ultrahigh reactivity provokes nanotoxicity: explanation of oral toxicity of nano-copper particles. Toxicology letters 2007;175(1-3):102-110.
29. 29. Sarkar A, et al. Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology 2011;290(2-3):208- 217.
30. 30. Manna P, et al. Contribution of nano-copper particles to in vivo liver dysfunction and cellular damage: Role of IκBα/NF-κB, MAPKs and mitochondrial signal. Nanotoxicology 2012;6(1):1-21.
31. 31. Prabhu BM, et al. Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat. Nanotoxicology 2010;4(2):150-160.
32. 32. Xu P, et al. Nano copper induced apoptosis in podocytes via increasing oxidative stress. Journal of hazardous materials 2012;241:279-286.
33. 33. Manke A, Wang L, Rojanasakul Y. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity 2013.
34. 34. Obert J, Cave M, Marsano L. Liver diseases. In Nutrition for the Primary Care Provider USA; Karger Publishers 2015;111:146-150.
35. 35. Li S, et al. The role of oxidative stress and antioxidants in liver diseases. International journal of molecular sciences 2015;16(11):26087-26124.
36. 36. De Andrade, KQ, et al. Oxidative stress and inflammation in hepatic diseases: therapeutic possibilities of N-acetylcysteine. International journal of molecular sciences 2015;16(12):30269-30308.
37. 37. Harvey A. Strategies for discovering drugs from previously unexplored natural products. Drug discovery today 2000;5(7):294-300.
38. 38. Al-Rubaei ZM, Mohammad TU, Ali LK. Effects of local curcumin on oxidative stress and total antioxidant capacity in vivo study. Pak J Biol Sci 2014;17(12):1237- 1241.
39. 39. Jain A, et al. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and environmental safety 2011;74(4):607-614.
40. 40. Wang J, et al. Protective effect of naringenin against lead-induced oxidative stress in rats. Biological trace element research 2012;146(3):354-359.