Quaercetin Improves Renal Functional Disorder and Dyslipidemia Caused by Acute Cadmium Exposure

Öz

Heavy metal toxicity and bioaccumulation caused severe damage to soil, water and environment as a result of industrialization/urbanization activities in developing and developed countries. This damage has affected different trophic levels including plants, animals and humans and has become a global concern. The use of various phytonutrients such as Quercetin (QE) has increased in recent years to avoid toxicity caused by heavy metals. Among different heavy metals, cadmium (Cd) toxicity is a major issue in the countries. Cd is a toxic heavy metal that can damage the kidneys and cause dysregulation in many lipid metabolic pathways. However, the number of studies on renal dysfunction and dyslipidemia caused by Cd is limited. We found that Cd causes renal dysfunction and dyslipidemia, and QE ameliorates these Cd-induced damages. Our results showed that Cd increased urea, uric acid, creatnine, alkene phosphatase (ALP), total bilirubin (TBIL) levels compared to the control group, while QE improved other parameters except TBIL. In addition, our findings showed that Cd increased total glyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) and lactate dehydrogenase (LDH) levels and decreased high-density lipoprotein (HDL) levels. It was noted that QE tended to improve this dyslipidemia picture. The data presented here demonstrated that QE has a clear protective role against dyslipidemia and renal function against Cd toxicity through its hypolipidemic and antioxidative action.

Anahtar Kelimeler

• Cadmium
• Kidney Functions
• Dyslipidemia

Kaynakça

1. Adedara, IA., Ego, VC., Subair, TI., Oyediran, O., & Farombi, EO. (2017). Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats. Neurochem. Res. 42(4):1219-1229.
2. Aguirre, L., Arias, N., Teresa Macarulla, M., Gracia, A., & P Portillo, M. (2011). Beneficial effects of quercetin on obesity and diabetes. Open Nutraceuticals J. 4(1): 189-198.
3. Almeida, AF., Borge, GIA., Piskula, M., Tudose, A., Tudoreanu, L., Valentová, K., Williamson, G., & Santos, CN. (2018). Bioavailability of Quercetin in Humans with a Focus on Interindividual Variation. Compr. Rev. Food Sci. Food Saf. 17(3):714-731.
4. Almeida, JA., Novelli, ELB., Dal Pai Silva, M., & Alves Júnior, R. (2001). Environmental cadmium exposure and metabolic responses of the Nile tilapia, Oreochromis niloticus. Environ. Pollut. 114(2):169-175.
5. Alshammari, GM., Al-Qahtani, WH., AlFaris, NA., Albekairi, NA., Alqahtani, S., Eid, R., Yagoub, AEA., Al-Harbi, LN., & Yahya, MA. (2021). Quercetin alleviates cadmium chloride-induced renal damage in rats by suppressing endoplasmic reticulum stress through SIRT1-dependent deacetylation of Xbp-1s and eIF2α. Biomed. Pharmacother. 141:111862.
6. Ansari, MN., Ganaie, MA., Rehman, NU., Alharthy, KM., Khan, TH., Imam, F., Ansari, MA., Al-Harbi, NO., Jan, BL., Sheikh, IA., & Hamad, AM. (2019). Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats. Saudi. Pharm. J. 27(5):673-681.
7. Aranami, F., Segawa, H., Furutani, J., Kuwahara, S., Tominaga, R., Hanabusa, E., Tatsumi, S., Kido, S., Ito, M., & Miyamoto, K. (2010). Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium. J. Med. Investig. 57(1,2):95-108.
8. Ateş, MB., & Hatipoğlu, D. (2022). Effect of nigella sativa oil on bisphenol a-induced hepatotoxicity in wistar albino rats: histopathological and biochemical investigation. Int. J. Agric. Environ. Food Sci. 6(3):402-409.

9. Bernhoft, RA. (2013). Cadmium Toxicity and Treatment. Sci. World J.. 2013(1):394652.
10. Bhaskar, S., Kumar, KS., Krishnan, K., Antony, H. (2013). Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition. 29(1):219-229.
11. Dorian, C., Gattone, VH., & Klaasen, CD. (1992). Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein (CdMT) by the proximal convoluted tubules—A light microscopic autoradiography study with 109CdMT. Toxicol. Appl. Pharmacol. 114(2):173-181.
12. Erdem, T., & Hatipoğlu, F. (2011). Pathology of single dose cadmium toxicity and investigations of protective effect of simultaneous chlorpromazine administrations in rats. Eurasian J. Vet. Sci. 27(1):45-58.
13. Fatima, G., Raza, AM., Hadi, N., Nigam, N., Mahdi, AA. (2019). Cadmium in Human Diseases: It's More than Just a Mere Metal. Indian J Clin Biochem. 34(4):371-378.
14. Fu, Z., & Xi, S. (2020). The effects of heavy metals on human metabolism. Toxicol. Mech. Methods. 30(3):167-176.
15. Gao, W., Pu, L., Chen, M., Wei, J., Xin, Z., Wang, Y., Yao, Z., Shi, T., & Guo, C. (2018). Glutathione homeostasis is significantly altered by quercetin via the Keap1/Nrf2 and MAPK signaling pathways in rats. J. Clin. Biochem. Nutr. 62(1):56-62.
16. George, M., Goyer, RA., & Delaquerriere-Richardson, L. (1976). Cadmium-metallothionein-induced nephropathy. Toxicol. Appl. Pharmacol. 38(2):399-408.
17. Gnoni, GV., Paglialonga, G., & Siculella, L. (2009). Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells. Eur. J. Clin. Invest. 39(9):761-768.
18. Goodarzi, Z., Karami, E., Yousefi, S., Dehdashti, A., Bandegi, AR., & Ghanbari, A. (2020). Hepatoprotective effect of atorvastatin on Cadmium chloride induced hepatotoxicity in rats. Life Sciences. 254:117770.
19. Hatipoglu, D., & Keskin, E. (2022). The effect of curcumin on some cytokines, antioxidants and liver function tests in rats induced by Aflatoxin B1. Heliyon. 8(7):e09890.
20. Hong, H., Xu, Y., Xu, J., Zhang, J., Xi, Y., Pi, H., Yang, L,, Yu, Z,, Wu, Q., Meng, Z., Ruan, W-S., Ren, Y., Xu, S., Lu, Y-Q., & Zhou, Z. (2021). Cadmium exposure impairs pancreatic β-cell function and exaggerates diabetes by disrupting lipid metabolism. Environ. Int. 149:106406.
21. Hosseini, A., Razavi, BM., Banach, M., & Hosseinzadeh, H. (2021). Quercetin and metabolic syndrome: A review. Phytother. Res. 35(10):5352-5364.
22. Huang, C-T., Chen, M-L., Huang, L-L., & Mao, I-F. (2002). Uric acid and urea in human sweat. Chin. J. Physiol. 45(3):109-116.
23. Järup, L., & Åkesson, A. (2009). Current status of cadmium as an environmental health problem. Toxicol. Appl. Pharmacol. 238(3):201-208.
24. Jeong, S-M., Kang, M-J., Choi, H-N., Kim, J-H., & Kim, J-I. (2012). Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr. Res. Pract. 6(3):201-207.
25. Johri, N., Jacquille, G., & Unwin, R. (2010). Heavy metal poisoning: the effects of cadmium on the kidney. BioMetals. 23(5):783-792.
26. Kayaaltı, Z., Akyüzlü, DK., & Söylemezoğlu, T. (2015). Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels. Environ. Res. 137:8-13.
27. Kido, T., Nogawa, K., Ishizaki, M., Honda, R., Tsuritani, I., Yamada, Y., Nakagawa, H., & Nishi, M. (1990). Long-term observation of serum creatinine and arterial blood pH in persons with cadmium-induced renal dysfunction. Arch. Environ. Health. 45(1):35-41.
28. Kısadere, İ., & Dönmez, N. (2019). The effects of quercetin on antioxidant system and some blood parameters in rats exposed to acute cadmium toxicity. Eurasian J. Vet. Sci. 35(2):66-70.
29. Kısadere, İ., Dönmez, N., & Dönmez, HH. (2019). The effects of quercetin on antioxidant and cytokine levels in rat hippocampus exposed to acute cadmium toxicity. J. Cell. Neurosci. Oxidative Stress. 11:10-10.
30. Kısadere, İ., Karaman, M., Aydın, MF., Donmez, N., & Usta, M. (2021). The protective effects of chitosan oligosaccharide (COS) on cadmium-induced neurotoxicity in Wistar rats. Arch. Environ. Occup. 77(9): 755-763
31. Kobori, M., Masumoto, S., Akimoto, Y., & Oike, H. (2011). Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice. Mol. Nutr. Food. Res. 55(4):530-540.
32. Larregle, EV., Varas, SM., Oliveros, LB., Martinez, LD., Antón, R., Marchevsky, E., & Giménez, MS. (2008). Lipid metabolism in liver of rat exposed to cadmium. Food Chem. Toxicol. 46(5):1786-1792.
33. Liu, Z., Lv, W., Huang, Y., Fan, B., Li, Y., Zhao, Y. (2016). Effects of cadmium on lipid metabolism in female estuarine crab, Chiromantes dehaani. Comp. Biochem. Physiol. Part - C: Toxicol. Pharmacol. 188:9-16.
34. Luevano, J., & Damodaran, C. (2014). A Review of Molecular Events of Cadmium-Induced Carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 33(3):183-194.
35. Madden, EF., & Fowler, BA. (2000). Mechanisms of nephrotoxicity from metal combinations: a review. Drug Chem Toxicol. 23(1):1-12.
36. Momeni, L., Fathi Moghadam, H., Hosseini, SA., & Nikbakht, M. (2019). Protective Role of Training and Selenium Consumption Against Renal Toxicity Induced by Cadmium in Rats. Mod. Care. J. 16(4):e96468.
37. Muselin, F., Cristina, RT., Dumitrescu, E., Doma, AO., Radulov, I., Berbecea, AA., Horablaga, A., Morariu, FE., Manea, DN., & Horablaga, NM. (2022). Quercetin Beneficial Role in the Homeostatic Variation of Certain Trace Elements in Dyslipidemic Mice. Evid.-based Complement. Altern. Med.. 2022:3299505.
38. Nordberg, GF. (1984). Chelating agents and cadmium toxicity: problems and prospects. Environ. Health. Perspect. 54:213-218.
39. Oguzturk, H., Ciftci, O., Aydin, M., Timurkaan, N., Beytur, A., & Yilmaz, F. (2012). Ameliorative effects of curcumin against acute cadmium toxicity on male reproductive system in rats. Andrologia. 44(4):243-249.
40. Pathak, N., & Khandelwal, S. (2007). Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicol. Lett. 169(2):95-108.
41. Pollack, AZ., Mumford, SL., Mendola, P., Perkins, NJ., Rotman, Y., Wactawski-Wende, J., & Schisterman, EF. (2015). Kidney Biomarkers Associated with Blood Lead, Mercury, and Cadmium in Premenopausal Women: A Prospective Cohort Study. J. Toxicol. Environ. Health Part A. 78(2):119-131.
42. Prabu, SM., Muthumani, M., & Shagirtha, K. (2013). Quercetin potentially attenuates cadmium induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. Eur. Rev. Med. Pharmacol. Sci. 17(5):582-595.
43. Prozialeck, WC., & Edwards, JR. (2012). Mechanisms of Cadmium-Induced Proximal Tubule Injury: New Insights with Implications for Biomonitoring and Therapeutic Interventions. J. Pharmacol. Exp. Ther. 343(1):2-12.
44. Renugadevi, J., &Milton Prabu, S. (2010). Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats. Exp. Toxicol. Pathol. 62(5):471-481.
45. Renugadevi, J., & Prabu, SM. (2009). Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology. 256(1):128-134.
46. Rogalska, J., Brzóska, MM., Roszczenko, A., & Moniuszko-Jakoniuk, J. (2009). Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem.-Biol. Interact. 177(2):142-152.
47. Samarghandian, S., Azimi-Nezhad, M., Shabestari, MM., Azad, FJ., Farkhondeh, & T., Bafandeh, F. (2015). Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats. Interdiscip. Toxicol. 8(3):151-154.
48. Satarug, S. (2018). Dietary Cadmium Intake and Its Effects on Kidneys. Toxics. 6(1):15.
49. Satarug, S., Haswell-Elkins, MR., & Moore, MR. (2007). Safe levels of cadmium intake to prevent renal toxicity in human subjects. Br. J. Nutr. 84(6):791-802.
50. Satarug, S., Ruangyuttikarn, W., Nishijo, M., & Ruiz, P. (2018). Urinary Cadmium Threshold to Prevent Kidney Disease Development. Toxics. 6(2):26.
51. Sato, M., & Kondoh, M. (2002). Recent Studies on Metallothionein: Protection Against Toxicity of Heavy Metals and Oxygen Free Radicals. Tohoku J. Exp. Med. 196(1):9-22.
52. Tang, Y., Gao, C., Xing, M., Li, Y., Zhu, L., Wang, D., Yang, X., Liu, L., & Yao, P. (2012). Quercetin prevents ethanol- induced dyslipidemia and mitochondrial oxidative damage. Food. Chem. Toxicol. 50(5):1194-1200.
53. Thévenod, F., & Wolff, NA. (2015). Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity. Metallomics. 8(1):17-42.
54. ul Haq, A., Mahmood, R., Ahmad, Z., ur Rehman, J., & Jilani, G. (2010). Association of serum uric acid with blood urea and serum creatinine. Pak. J. Physiol. 6(2):46-49.
55. Wenk, MR. (2005). The emerging field of lipidomics. Nat. Rev. Drug Discov. 4(7):594-610.
56. Xu, D., Hu, M-J., Wang, Y-Q., & Cui, Y-L. (2019). Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules. 24(6):1123.
57. Yuan, Y., Ma, S., Qi, Y., Wei, X., Cai, H., Dong, L., Lu, Y., Zhang, Y., & Guo, Q. (2016). Quercetin inhibited cadmium- induced autophagy in the mouse kidney via inhibition of oxidative stress. J. Toxicol. Pathol. 29(4):247-252