Ameliorative effect of zingerone on cadmium-induced nephrotoxicity in adult wistar rats


Abstract views: 84 / PDF downloads: 38

Authors

DOI:

https://doi.org/10.62313/ijpbp.2024.238

Keywords:

Zingerone, Oxidative stress, Renal toxicity, Cadmium, Creatinine, Urea

Abstract

Exposure to heavy metals like cadmium has been reported to cause severe kidney damage through oxidative stress and inflammation. Zingerone is a bioactive compound present in ginger, it contains significant anti-oxidative and anti-inflammatory properties. This study aims to investigate the anti-oxidative and therapeutic role of zingerone on cadmium-induced nephrotoxicity. Thirty (30) adult male rats were divided into 6 groups (A-F) of 5 rats each (n = 5) randomly [A: normal control (normal saline), B: cadmium-exposed (5 mg/kg of cadmium only), C: zingerone-alone, D-F: 5 mg/kg of cadmium + 50 mg/kg, 100mg/kg, 200 mg/kg of zingerone, respectively]. Nephrotoxicity was induced by oral administration of cadmium chloride (CdCl₂), followed by zingerone treatment orally. Renal function markers (serum creatinine and urea level), oxidative stress markers (superoxide dismutases, catalase, malondialdehyde), and histopathological investigations of the kidney were assessed to evaluate the effects. Cadmium administration resulted in significant renal dysfunction, characterized by elevated serum creatinine, urea, and kidney malondialdehyde levels, along with reduced antioxidant enzyme activities (superoxide dismutase and catalase). Histopathological evaluation showed extensive kidney damage characterized by renal tubular damage, necrosis, and inflammation. Zingerone treatment significantly ameliorated these alterations, restoring renal function markers, reducing oxidative stress, and improving the histological architecture of the kidney. These findings suggest that zingerone exerts an anti-oxidative and therapeutic effect against cadmium-induced nephrotoxicity. According to these findings, zingerone shows potential as a therapeutic approach for kidney impairment caused by exposure to heavy metals.

References

Aebi, H. (1984). Catalase in vitro (Vol. 105): Elsevier. https://doi.org/10.1016/S0076-6879(84)05016-3 DOI: https://doi.org/10.1016/S0076-6879(84)05016-3

Ahmad, B., Rehman, M. U., Amin, I., Arif, A., Rasool, S., Bhat, S. A., Afzal, I., Hussain, I., Bilal, S., & Mir, M. U. R. (2015). A review on pharmacological properties of zingerone (4‐(4‐Hydroxy‐3‐methoxyphenyl)‐2‐butanone). The Scientific World Journal, 2015, 816364. http://dx.doi.org/10.1155/2015/816364 DOI: https://doi.org/10.1155/2015/816364

Akinyemi, A. J., Faboya, O. L., Paul, A. A., Olayide, I., Faboya, O. A., & Oluwasola, T. A. (2018). Nephroprotective effect of essential oils from ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes against cadmium-induced nephrotoxicity in rats. Journal of Oleo Science, 67(10), 1339-1345. https://doi.org/10.1155/2018/4109491 DOI: https://doi.org/10.5650/jos.ess18115

Al-Naimi, M. S., Rasheed, H. A., Hussien, N. R., Al-Kuraishy, H. M., & Al-Gareeb, A. I. (2019). Nephrotoxicity: Role and significance of renal biomarkers in the early detection of acute renal injury. Journal of Advanced Pharmaceutical Technology & Research, 10(3), 95-99. https://doi.org/10.4103/japtr.JAPTR_336_18 DOI: https://doi.org/10.4103/japtr.JAPTR_336_18

Alam, M. F. (2018). Neuroprotective effects of zingerone against carbon tetrachloride (CCl4) induced brain mitochondrial toxicity in Swiss albino mice. Journal of Applied and Natural Science, 10(2), 548-552. https://doi.org/10.31018/jans.v10i2.1734 DOI: https://doi.org/10.31018/jans.v10i2.1734

Alibakhshi, T., Khodayar, M. J., Khorsandi, L., Rashno, M., & Zeidooni, L. (2018). Protective effects of zingerone on oxidative stress and inflammation in cisplatin-induced rat nephrotoxicity. Biomedicine & Pharmacotherapy, 105, 225-232. https://doi.org/10.1016/j.biopha.2018.05.085 DOI: https://doi.org/10.1016/j.biopha.2018.05.085

Amin, I., Hussain, I., Rehman, M. U., Mir, B. A., Ganaie, S. A., Ahmad, S. B., Mir, M. U. R., Shanaz, S., Muzamil, S., & Arafah, A. (2021). Zingerone prevents lead‐induced toxicity in liver and kidney tissues by regulating the oxidative damage in Wistar rats. Journal of Food Biochemistry, 45(3), e13241. https://doi.org/10.1111/jfbc.13241 DOI: https://doi.org/10.1111/jfbc.13241

Anusuya, N., Durgadevi, P., Dhinek, A., & Mythily, S. (2013). Nephroprotective effect of ethanolic extract of garlic (Allium sativum L.) on cisplatin induced nephrotoxicity in male wistar rats. Asian Journal of Pharmaceutical and Clinical Research, 6(4), 97-100.

Augustine, O., Emeka, A. G., Ezinne, O., Chidinma, U. O. O., Emmanuel, O. N., & Oluwatoyin, M. E. (2023). Nephroprotective Properties of Aqueous Extract of Ficus exasperata on Gentamicin-Induced Nephrotoxicity. Acta Scientific Anatomy, 2(4), 12-18.

Bannister, J., & Calabrese, L. (1987). Assays for superoxide dismutase. In D. Glick (Ed.), Methods of Biochemical Analysis (pp. 279–312): John Wiley & Sons, New York, NY, USA. DOI: https://doi.org/10.1002/9780470110539.ch5

Bernard, A. (2008). Cadmium & its adverse effects on human health. Indian Journal of Medical Research, 128(4), 557-564.

Bernhoft, R. A. (2013). Cadmium toxicity and treatment. The Scientific World Journal, 2013, 394652. https://doi.org/10.1155/2013/394652 DOI: https://doi.org/10.1155/2013/394652

Ceretta, L. B., Réus, G. Z., Abelaira, H. M., Ribeiro, K. F., Zappellini, G., Felisbino, F. F., Steckert, A. V., Dal-Pizzol, F., & Quevedo, J. (2012). Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan‐induced diabetic rats. Journal of Diabetes Research, 2012, 302682. https://doi.org/10.1155/2012/302682 DOI: https://doi.org/10.1155/2012/302682

Chargui, A., Zekri, S., Jacquillet, G., Rubera, I., Ilie, M., Belaid, A., Duranton, C., Tauc, M., Hofman, P., & Poujeol, P. (2011). Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicological Sciences, 121(1), 31-42. https://doi.org/10.1093/toxsci/kfr031 DOI: https://doi.org/10.1093/toxsci/kfr031

Chiş, I., Baltaru, D., Dumitrovici, A., Coseriu, A., Radu, B., Moldovan, R., & Mureşan, A. (2016). Quercetin ameliorate oxidative/nitrosative stress in the brain of rats exposed to intermittent hypobaric hypoxia. Revista Virtual de Quimica, 8(2), 369-383. https://doi.org/10.5935/1984-6835.20160027 DOI: https://doi.org/10.5935/1984-6835.20160027

Conti, M., Morand, P., Levillain, P., & Lemonnier, A. (1991). Improved fluorometric determination of malonaldehyde. Clinical Chemistry, 37(7), 1273-1275. https://doi.org/10.1093/clinchem/37.7.1273 DOI: https://doi.org/10.1093/clinchem/37.7.1273

Das, S. C., & Al-Naemi, H. A. (2019). Cadmium toxicity: oxidative stress, inflammation and tissue injury. Scientific Research Publishing, 7, 144-163. http://dx.doi.org/10.4236/odem.2019.74012 DOI: https://doi.org/10.4236/odem.2019.74012

Dawood, S. M., Mumtaz, F., & Padiya, R. (2022). Zingerone alleviates cadmium-induced nephrotoxicity in rats via its antioxidant and anti-apoptotic properties. Revista de Ciências Farmacêuticas Básica e Aplicada, 43, e759. https://doi.org/10.4322/2179-443X.0759 DOI: https://doi.org/10.4322/2179-443X.0759

Ekor, M. (2014). Nephrotoxicity and nephroprotective potential of African medicinal plants. In V. Kuete (Ed.), Toxicological Survey of African Medicinal Plants (pp. 357-393): Elsevier. https://doi.org/10.1016/B978-0-12-800018-2.00012-1 DOI: https://doi.org/10.1016/B978-0-12-800018-2.00012-1

Emeka, A. G., Augustine, O., Chidinma, O. E., & Nto, N. J. (2023). Zingerone improves memory impairment in Wistar rats exposed to cadmium via modulation of redox imbalance. Journal of Krishna Institute of Medical Sciences, 12(1), 3-16.

Fatima, G., Raza, A. M., Hadi, N., Nigam, N., & Mahdi, A. A. (2019). Cadmium in human diseases: It’s more than just a mere metal. Indian Journal of Clinical Biochemistry, 34(4), 371-378. https://doi.org/10.1007/s12291-019-00839-8 DOI: https://doi.org/10.1007/s12291-019-00839-8

Finn, W. F., & Porter, G. A. (2003). Urinary biomarkers and nephrotoxicity. In M. de Broe, G. Porter, W. Bennett, & G. Verpooten (Eds.), Clinical Nephrotoxins: Renal Injury from Drugs and Chemicals (pp. 621-655): Springer, Dordrecht. https://doi.org/10.1007/1-4020-2586-6_33 DOI: https://doi.org/10.1007/1-4020-2586-6_33

Genchi, G., Sinicropi, M. S., Lauria, G., Carocci, A., & Catalano, A. (2020). The effects of cadmium toxicity. International Journal of Environmental Research and Public Health, 17(11), 3782. https://doi.org/10.3390/ijerph17113782 DOI: https://doi.org/10.3390/ijerph17113782

Hogervorst, J., Plusquin, M., Vangronsveld, J., Nawrot, T., Cuypers, A., Van Hecke, E., Roels, H. A., Carleer, R., & Staessen, J. A. (2007). House dust as possible route of environmental exposure to cadmium and lead in the adult general population. Environmental Research, 103(1), 30-37. https://doi.org/10.1016/j.envres.2006.05.009 DOI: https://doi.org/10.1016/j.envres.2006.05.009

Hosseinzadeh, A., Goudarzi, M., Karimi, M. Y., Khorsandi, L., Mehrzadi, S., & Mombeini, M. A. (2020). Zingerone ameliorates gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29, 971-980. https://doi.org/10.1007/s00580-020-03129-5 DOI: https://doi.org/10.1007/s00580-020-03129-5

Jamakala, O., & Rani, A. U. (2014). Mitigating role of zinc and iron against cadmium induced toxicity in liver and kidney of male albino rat: a study with reference to metallothionein quantification. International Journal of Pharmacy and Pharmaceutical Sciences, 6(9), 411-417.

Kandemir, F. M., Yildirim, S., Caglayan, C., Kucukler, S., & Eser, G. (2019). Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats. Environmental Science and Pollution Research, 26, 22562-22574. https://doi.org/10.1007/s11356-019-05505-3 DOI: https://doi.org/10.1007/s11356-019-05505-3

Kim, K. S., Lim, H. J., Lim, J. S., Son, J. Y., Lee, J., Lee, B. M., Chang, S. C., & Kim, H. S. (2018). Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats. Food and Chemical Toxicology, 114, 34-40. https://doi.org/10.1016/j.fct.2018.02.007 DOI: https://doi.org/10.1016/j.fct.2018.02.007

Kumar, L., Harjai, K., & Chhibber, S. (2014). Recent update on multiple pharmacological benefits of zingerone: a quick review. American Journal of Phytomedicine and Clinical Therapeutics, 2, 693-704.

Lee, Y. K., Park, E. Y., Kim, S., Son, J. Y., Kim, T. H., Kang, W. G., Jeong, T. C., Kim, K. B., Kwack, S. J., & Lee, J. (2014). Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles in sprague-dawley male rats. Journal of Toxicology and Environmental Health, Part A, 77(22-24), 1384-1398. https://doi.org/10.1080/15287394.2014.951755 DOI: https://doi.org/10.1080/15287394.2014.951755

Mani, V., Siddique, A. I., Arivalagan, S., Thomas, N. S., & Namasivayam, N. (2016). Zingerone ameliorates hepatic and renal damage in alcohol-induced toxicity in experimental rats. International Journal of Nutrition, Pharmacology, Neurological Diseases, 6(3), 125-132. https://doi.org/10.4103/2231-0738.184585 DOI: https://doi.org/10.4103/2231-0738.184585

Mashhadi, N. S., Ghiasvand, R., Askari, G., Hariri, M., Darvishi, L., & Mofid, M. R. (2013). Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence. International Journal of Preventive Medicine, 4(Suppl 1), S36-S42.

Matović, V., Buha, A., Ðukić-Ćosić, D., & Bulat, Z. (2015). Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food and Chemical Toxicology, 78, 130-140. https://doi.org/10.1016/j.fct.2015.02.011 DOI: https://doi.org/10.1016/j.fct.2015.02.011

Mehrzadi, S., Khalili, H., Fatemi, I., Malayeri, A., Siahpoosh, A., & Goudarzi, M. (2021). Zingerone mitigates carrageenan-induced inflammation through antioxidant and anti-inflammatory activities. Inflammation, 44, 186-193. https://doi.org/10.1007/s10753-020-01320-y DOI: https://doi.org/10.1007/s10753-020-01320-y

Munisamy, R., Ismail, S. N. S., & Praveena, S. M. (2013). Cadmium exposure via food crops: a case study of intensive farming area. American Journal of Applied Sciences, 10(10), 1252-1262. https://doi.org/10.3844/ajassp.2013.1252.1262 DOI: https://doi.org/10.3844/ajassp.2013.1252.1262

Olubunmi, O. P., Yinka, O. S., Oladele, O. J., John, O. A., & Boluwatife, B. D. (2017). Histomorphological Changes in Kidney Associated with the Ethanolic Extracts of the Leaves of Phyllanthus amarus in Cadmium Induced Kidney Damage in Experimental Animals. International Journal of Clinical and Developmental Anatomy, 3(4), 25-35. https://doi.org/10.11648/j.ijcda.20170304.12 DOI: https://doi.org/10.11648/j.ijcda.20170304.12

Onwuka, F. C., Erhabor, O., Eteng, M., & Umoh, I. (2011). Protective effects of ginger toward cadmium-induced testes and kidney lipid peroxidation and hematological impairment in albino rats. Journal of Medicinal Food, 14(7-8), 817-821. https://doi.org/10.1089/jmf.2010.0106 DOI: https://doi.org/10.1089/jmf.2010.0106

Oviosun, A., Emeka, A. G., Chidinma, O. E., Emmanuel, O. N., Ehizokhale, E. S., & Anthony, E. I. (2023). Therapeutic Properties of Ficus exasperata Extract on Gentamicin Induced Kidney Damage. European Journal of Pharmaceutical and Medical Research, 10(10), 50-55.

Peana, M., Pelucelli, A., Chasapis, C. T., Perlepes, S. P., Bekiari, V., Medici, S., & Zoroddu, M. A. (2022). Biological effects of human exposure to environmental cadmium. Biomolecules, 13(1), 36. https://doi.org/10.3390/biom13010036 DOI: https://doi.org/10.3390/biom13010036

Safhi, M. M. (2015). Zingerone protects the tellurium toxicity in the brain mitochondria of rats. Metabolomics, 5(4), 156. DOI: https://doi.org/10.4172/2153-0769.1000156

Salama, M. E., Adel, M., Helal, G., & El-Shafey, M. (2019). Role of oxidative stress, apoptosis and autophagy in cadmium-induced renal injury in rats: renoprotective effect of ghrelin. Bulletin of Egyptian Society for Physiological Sciences, 39(2), 271-285. https://doi.org/10.1016/j.lfs.2021.120121 DOI: https://doi.org/10.21608/besps.2019.14414.1025

Sevastre-Berghian, A. C., Făgărăsan, V., Toma, V. A., Bâldea, I., Olteanu, D., Moldovan, R., Decea, N., Filip, G. A., & Clichici, S. V. (2017). Curcumin reverses the diazepam‐induced cognitive impairment by modulation of oxidative stress and ERK 1/2/NF‐κB pathway in brain. Oxidative Medicine and Cellular Longevity, 2017(1), 3037876. https://doi.org/10.1155/2017/3037876 DOI: https://doi.org/10.1155/2017/3037876

Shati, A. A. (2011). Effects of Origanum majorana L. on cadmium induced hepatotoxicity and nephrotoxicity in albino rats. Saudi Medical Journal, 32(8), 797-805.

Spencer, L., Bancroft, J., Bancroft, J., & Gamble, M. (2012). Tissue processing: (pp. 105–123). Netherlands, Amsterdam: Elsevier Health Sciences. DOI: https://doi.org/10.1016/B978-0-7020-4226-3.00006-8

Stevens, L. A., Coresh, J., Greene, T., & Levey, A. S. (2006). Assessing kidney function—measured and estimated glomerular filtration rate. New England Journal of Medicine, 354(23), 2473-2483. https://doi.org/10.1056/NEJMra054415 DOI: https://doi.org/10.1056/NEJMra054415

Türk, E., Güvenç, M., Cellat, M., Uyar, A., Kuzu, M., Ağgül, A. G., & Kırbaş, A. (2022). Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats. Drug and Chemical Toxicology, 45(3), 1054-1065. https://doi.org/10.1080/01480545.2020.1804397 DOI: https://doi.org/10.1080/01480545.2020.1804397

Vijaya, P., Kaur, H., Garg, N., & Sharma, S. (2020). Protective and therapeutic effects of garlic and tomato on cadmium-induced neuropathology in mice. The Journal of Basic and Applied Zoology, 81, 23. https://doi.org/10.1186/s41936-020-00160-4 DOI: https://doi.org/10.1186/s41936-020-00160-4

Vukićević, T. (2012). Toxic effects of cadmium. Acta Medica Mediterranea, 51(4), 65-70. https://doi.org/10.5633/amm.2012.0410

Wachira, F. N., Areba, G., Ngure, R., Khalid, R., Maloba, F., Nyaga, N., Moseti, K., Ngotho, M., Wanyoko, J., & Karori, S. (2019). Neuroprotective effects of tea against cadmium toxicity. Bioactive Compounds in Health and Disease, 2(12), 230-246. DOI: https://doi.org/10.31989/bchd.v2i12.684

Yan, L. J., & Allen, D. C. (2021). Cadmium-induced kidney injury: Oxidative damage as a unifying mechanism. Biomolecules, 11(11), 1575. https://doi.org/10.3390/biom11111575 DOI: https://doi.org/10.3390/biom11111575

Zhang, Y. X. (2012). Simultaneous determination of five gingerols in raw and processed ginger by HPLC. Chinese Pharmaceutical Journal, 24, 471-474.

Downloads

Published

30.11.2024

How to Cite

Oviosun, A., Anyanwu, E. G., Oviosun, E. C., & Blasius Okechukwu, O. (2024). Ameliorative effect of zingerone on cadmium-induced nephrotoxicity in adult wistar rats. International Journal of Plant Based Pharmaceuticals, 4(2), 118–124. https://doi.org/10.62313/ijpbp.2024.238

Issue

Section

Research Articles
Received 2024-08-17
Accepted 2024-11-28
Published 2024-11-30