Zinc oxide nanoparticles synthesized with Berberis vulgaris L. ameliorate cyclophosphamide-induced nephrotoxicity in rats

Reza Mohammadian , Nader Goodarzi , Mohsen Akbaribazm , Hadi Cheraghi

Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (4) : 158 -168.

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Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (4) : 158 -168. DOI: 10.4103/apjtb.apjtb_696_24
Original Article

Zinc oxide nanoparticles synthesized with Berberis vulgaris L. ameliorate cyclophosphamide-induced nephrotoxicity in rats

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Abstract

Objective: To examine the protective effects of green-synthesized zinc oxide nanoparticles with Berberis vulgaris L. fruit aqueous extract (BVZnONPs) on cyclophosphamide (CP)-induced nephrotoxicity in Wistar rats.

Methods: 35 Adult male Wistar rats were divided into 5 groups: normal, BVZnONPs (20 mg/kg), CP (100 mg/kg), and 2 cotreatment groups receiving CP with BVZnONPs (10 and 20 mg/ kg). All treatments were administered intraperitoneally for 28 days. Serum levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, nitric oxide) and kidney function parameters (creatinine, total protein, blood urea nitrogen) were measured. The expressions of p53 and Bcl-2 proteins were assessed via immunohistochemical assay while kidney volume and substructures were estimated stereologically.

Results: CP induced nephrotoxicity with significant increases (P<0.05) in nitric oxide, creatinine, and blood urea nitrogen levels, and decreases (P<0.05) in catalase, superoxide dismutase, and glutathione peroxidase levels. It also increased p53 protein expression and decreased Bcl-2 protein expression. Treatment with BVZnONPs significantly increased (P<0.05) antioxidant enzyme levels and decreased nitric oxide levels in the 20 mg/kg group compared to CP. Blood urea nitrogen and creatinine levels were significantly reduced in the BVZnONPs-treated groups, with greater effects at 20 mg/kg. However, total protein serum levels were not significant (P>0.05) in the BVZnONPs-treated groups compared to CP.

Conclusions: These findings suggest that BVZnONPs can mitigate CP- induced nephrotoxicity, likely due to their antioxidant and anti-apoptotic properties, though longer treatment duration may be necessary for tissue- level improvements.

Keywords

Nanoparticle / Berberis vulgaris L / Barberry / Kidney / Zinc oxide / Chemotherapy

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Reza Mohammadian, Nader Goodarzi, Mohsen Akbaribazm, Hadi Cheraghi. Zinc oxide nanoparticles synthesized with Berberis vulgaris L. ameliorate cyclophosphamide-induced nephrotoxicity in rats. Asian Pacific Journal of Tropical Biomedicine, 2025, 15(4): 158-168 DOI:10.4103/apjtb.apjtb_696_24

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The authors received no extramural funding for the study.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

RM contributed to animal handling, treatment, and imaging procedures. NG contributed to writing the draft, conceptualization, and supervising the project. HC conducted laboratory tests, and MAB contributed to writing the draft and performing statistical analysis.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1]

Desai RJ, Kazarov CL, Wong A, Kane-Gill SL. Kidney damage and stress biomarkers for early identification of drug-induced kidney injury: A systematic review. Drug Saf 2022; 45(8): 839-852.

[2]

Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet 2021; 398(10302): 786-802.

[3]

Yin Q, Xiong H. Chemotherapy-induced nephrotoxicity was improved by crocin in mouse model. Eur J Histochem 2022; 66(4): 3541.

[4]

Ayza MA, Zewdie KA, Yigzaw EF, Ayele SG, Tesfaye BA, Tafere GG, et al. Potential protective effects of antioxidants against cyclophosphamide- induced nephrotoxicity. Int J Nephrol 2022; 2022(1): 5096825.

[5]

Qaed E, Almaamari A, Alyafeai E, Sultan M, Aldahmash W, Mahyoub MA, et al. Phosphocreatine attenuates doxorubicin-induced nephrotoxicity through inhibition of apoptosis and restore mitochondrial function via activation of Nrf2 and PGC-1α pathways. Chem Biol Interact 2024; 400. doi: 10.1016/j.cbi.2024.111147.

[6]

Ayza MA, Zewdie KA, Tesfaye BA, Wondafrash DZ, Berhe AH. The role of antioxidants in ameliorating cyclophosphamide-induced cardiotoxicity. Oxid Med Cell Longev 2020; 2020(1). doi: 10.1155/2020/4965171.

[7]

El-Shabrawy M, Mishriki A, Attia H, Emad Aboulhoda B, Emam M, Wanas H. Protective effect of tolvaptan against cyclophosphamide- induced nephrotoxicity in rat models. Pharmacol Res Perspect 2020; 8(5): e00659.

[8]

Özatik FY, Özatik O, Tekşen Y, Koçak H, Ari NS, Ünel ÇÇ. Dose- dependent effect of hydrogen sulfide in cyclophosphamide-induced hepatotoxicity in rats. Turk J Gastroenterol 2023; 34(6): 626-634.

[9]

El Kiki SM, Omran MM, Mansour HH, Hasan HF. Metformin and/ or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats. Mol Biol Rep 2020; 47: 5115-5126.

[10]

Khoshandam A, Imenshahidi M, Hosseinzadeh H. Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review. Phytother Res 2022; 36(11): 4063-4079.

[11]

Shakeri F, Kiani S, Rahimi G, Boskabady MH. Anti-inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review. Phytother Res 2024; 38(4): 1882-1902.

[12]

Hallajzadeh J, Maleki Dana P, Mobini M, Asemi Z, Mansournia MA, Sharifi M, et al. Targeting of oncogenic signaling pathways by berberine for treatment of colorectal cancer. Med Oncol 2020; 37(6): 49. doi: 10.1007/s12032-020-01367-9.

[13]

Derakhshani E, Asri M, Naghizadeh A. Plant-based green synthesis of copper oxide nanoparticles using Berberis vulgaris leaf extract: An update on their applications in antibacterial activity. Bionanoscience 2023; 13(1): 212-218.

[14]

Salayová A, Bedlovičová Z, Daneu N, Baláž M, Lukáčová Bujnáková Z, Balážová E, et al. Green synthesis of silver nanoparticles with antibacterial activity using various medicinal plant extracts: Morphology and antibacterial efficacy. Nanomater 2021; 11(4). doi: 10.3390/nano11041005.

[15]

Marumo A, Omori I, Tara S, Otsuka Y, Konuma R, Adachi H, et al. Cyclophosphamide-induced cardiotoxicity at conditioning for allogeneic hematopoietic stem cell transplantation would occur among the patients treated with 120 mg/kg or less. Asian Pac J Clin Oncol 2022; 18(5): e507-e514.

[16]

Akbaribazm M, Goodarzi N, Rahimi M, Naseri L, Khazaei M. Anti-inflammatory, anti-oxidative and anti-apoptotic effects of Heracleum persicum L. extract on rats with gentamicin-induced nephrotoxicity. Asian Pac J Trop Biomed 2021; 11(2): 47-58.

[17]

Akbari M, Goodarzi N, Tavafi M. Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney. Anat Sci Int 2017; 92: 267-274.

[18]

Zangeneh MM, Goodarzi N, Zangeneh A, Tahvilian R, Najafi F. Amelioration of renal structural changes in STZ-induced diabetic mice with ethanolic extract of Allium saralicum RM Fritsch. Comp Clin Pathol 2018; 27: 861-867.

[19]

Bazm MA, Khazaei M, Ghanbari E, Naseri L. Protective effect of Vaccinium arctostaphylos L. fruit extract on gentamicin-induced nephrotoxicity in rats. J Comp Pathol 2018; 27: 1327-1334.

[20]

Qi R, Wang J, Jiang Y, Qiu Y, Xu M, Rong R, et al. Snail-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2/M arrest in the progression of renal fibrosis via NF-KB-mediated inflammation. Cell Death Dis 2021; 12(1): 44. doi: 10.1038/s41419-020-03322-y.

[21]

El-Serafi I, Steele S. Cyclophosphamide pharmacogenomic variation in cancer treatment and its effect on bioactivation and pharmacokinetics. Adv Pharmacol Pharm Sci 2024; 2024(1): 4862706.

[22]

Ayza MA, Zewdie KA, Yigzaw EF, Ayele SG, Tesfaye BA, Tafere GG, et al. Potential protective effects of antioxidants against cyclophosphamide-induced nephrotoxicity. Int J Nephrol 2022; 2022(1). doi: 10.1155/2022/5096825.

[23]

Ou Z, Zhu L, Huang C, Ma C, Kong L, Lin X, et al. Betulinic acid attenuates cyclophosphamide-induced intestinal mucosa injury by inhibiting the NF-kB/MAPK signaling pathways and activating the Nrf2 signaling pathway. Ecotoxicol Environ Saf 2021; 225. doi: 10.1016/j.ecoenv.2021.112746.

[24]

Abulyazid I, Abd Elhalim SA, Sharada HM, Aboulthana WM, Abd Elhalim ST. Hepatoprotective effect of carob pods extract (Ceratonia siliqua L.) against cyclophosphamide induced alterations in rats. Int J Curr Pharm Rev Res 2017; 8(2): 149-162.

[25]

Goudarzi M, Khodayar MJ, Hosseini Tabatabaei SMT, Ghaznavi H, Fatemi I, Mehrzadi S. Pretreatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice. Fundam Clin Pharmacol 2017; 31(6): 625-635.

[26]

Temel Y, Kucukler S, Yildirim S, Caglayan C, Kandemir FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Arch. Pharmacol 2020; 393: 325-337.

[27]

Chen L, Xiong X, Hou X, Wei H, Zhai J, Xia T, et al. Wuzhi capsule regulates chloroacetaldehyde pharmacokinetics behaviour and alleviates high-dose cyclophosphamide-induced nephrotoxicity and neurotoxicity in rats. Basic Clin Pharmacol Toxicol 2019; 125(2): 142-151.

[28]

Hammodi HZ, Al-Shawi NN. Protective effect of daidzein on ifosfamide- induced neurotoxicity via improving some selected oxidative stress parameters in male rats. Iraqi J Pharm Sci 2023; 32(Suppl): 53-60.

[29]

El Kiki SM, Omran MM, Mansour HH, Hasan HF. Metformin and/ or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats. Mol Biol Rep 2020; 47: 5115-5126.

[30]

Mombeini MA, Kalantar H, Sadeghi E, Goudarzi M, Khalili H, Kalantar M. Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice. Naunyn-Schmiedeberg’s Arch Pharmacol 2022; 395(2): 187-194.

[31]

Adil M, Kandhare AD, Dalvi G, Ghosh P, Venkata S, Raygude KS, et al. Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Renal Fail 2016; 38(6): 996-1006.

[32]

Allameh H, Fatemi I, Malayeri AR, Nesari A, Mehrzadi S, Goudarzi M. Pretreatment with berberine protects against cisplatin-induced renal injury in male Wistar rats. Naunyn-Schmiedeberg’ Arch Pharmacol 2020; 393: 1825-1833.

[33]

Gholampour F, Masoudi R, Khaledi M, Rooyeh MM, Farzad SH, Ataellahi F, et al. Berberis integerrima hydro-alcoholic root extract and its constituent berberine protect against cisplatin-induced nephro-and hepato-toxicity. Am J Med Sci 2022; 364(1): 76-87.

[34]

Och A, Olech M, Bąk K, Kanak S, Cwener A, Cieśla M, et al. Evaluation of the antioxidant and anti-lipoxygenase activity of Berberis vulgaris L. leaves, fruits, and stem and their LC MS/MS polyphenolic profile. Antioxidants 2023; 12(7). doi: 10.3390/antiox12071467.

[35]

Rafiee F, Nejati V, Heidari R, Ashraf H. Protective effect of methanolic extract of Berberis integerrima Bunge. root on carbon tetrachloride- induced testicular injury in Wistar rats. Int J Reprod Biomed 2016; 14(2): 133-140.

[36]

Sonei A, Fazelipour S, Kanaani L, Jahromy MH. Protective effects of Berberis vulgaris on diazinon-induced brain damage in young male mice. Prev Nutr Food Sci 2020; 25(1): 65-70.

[37]

Hassanein EH, Ibrahim IM, Abd-Alhameed EK, Mohamed NM, Ross SA. Protective effects of berberine on various kidney diseases: Emphasis on the promising effects and the underlined molecular mechanisms. Life Sci 2022; 306. doi: 10.1016/j.lfs.2022.120697.

[38]

Gholampour F, Keikha S. Berberine protects the liver and kidney against functional disorders and histological damages induced by ferrous sulfate. Iran J Basic Med Sci 2018; 21(5): 476-482.

[39]

Abdel-Raheem IT, Abdel-Ghany AA, Mohamed GA. Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats. Biol Pharm Bull 2009; 32(1): 61-67.

[40]

Almaghrabi OA. Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney. Saudi J Biol Sci 2015; 22(2): 227-231.

[41]

Morales AI, Vicente-Sánchez C, Jerkic M, Santiago JM, Sánchez-González PD, Pérez-Barriocanal F, et al. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. Toxicol Appl Pharmacol 2006; 210(1-2): 128-135.

[42]

Bakir A, Suat E, Yüksek S, Gokhan OTO. The protective effect of Rheum Ribes L. and quercetin on protein carbonyl levels against carbon tetrachloride-induced liver and kidney damage in the rats. Clin Exp Health Sci 2022; 12(3): 587-593.

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