Sinapic acid attenuated nephrotoxicity against Cyclophosphamide in mice model: A histochemical, immunohistochemical and histopathological evaluation | ||
Iranian Journal of Basic Medical Sciences | ||
مقاله 13، دوره 28، شماره 5، مرداد 2025، صفحه 655-661 اصل مقاله (511.44 K) | ||
نوع مقاله: Original Article | ||
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.83903.18155 | ||
نویسندگان | ||
Saeed Raoof1، 2؛ Shiva Rezaei1، 2؛ Mehryar Zargari3؛ Masooreh Mirzaei1؛ Seyed Jalal Hosseinimehr4؛ Abbasali Karimpour Malekshah1؛ Fereshteh Talebpour Amiri* 1 | ||
1Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran | ||
2Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran | ||
3Department of Biochemistry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran | ||
4Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran | ||
چکیده | ||
Objective(s): Cyclophosphamide (CP) is a chemotherapeutic drug used to treat various tumors. It causes nephrotoxicity by producing reactive oxygen species. Sinapic acid (SA) exhibits anti-oxidant, antiapoptotic, and anti-inflammatory activities at low doses as a phenylpropanoid. This study aimed to investigate the protective effects of SA on SP-induced renal injury. Materials and Methods: Forty-eight BALB/c mice were randomly divided into control, SA (for seven consecutive days, with two doses of 5 and 10 mg/kg), CP (single dose, 200 mg/kg), and CP + SA (5 and 10 mg/kg). On the 10th day of the study, mice were examined by renal function markers (Urea and Creatinine), oxidative stress markers (MDA and GSH), histopathological, and immunohistochemical assays (caspase-3 and NF-kB kidney). Results: MDA levels increased and GSH levels decreased significantly in CP-treated mice. In addition, the histopathological structure of the kidney tissue in CP-treated mice showed significantly severe kidney tissue damage associated with increased urea and creatinine. The administration of SA in CP-treated mice significantly reduced serum urea and creatinine concentrations. In addition, the immunohistochemical staining of caspase- 3 and NF-kB decreased significantly in the CP + SA group compared to CP-treated mice. Conclusion: Overall, our study suggests that sinapic acid, a substance with antioxidant, antiapoptotic, and anti-inflammatory properties, can be used as a complementary therapy to protect nephrotoxicity against CP. | ||
کلیدواژهها | ||
Caspase-3؛ Cyclophosphamide؛ Nephrotoxicity؛ NF- kB؛ Oxidative stress؛ Sinapic acid | ||
مراجع | ||
1. Puyo S, Montaudon D, Pourquier P. From old alkylating agents to new minor groove binders. Crit Rev Oncol Hematol 2014; 89:43-61. 2. Highley MS, Landuyt B, Prenen H, Harper PG, De Bruijn EA. The nitrogen mustards. Pharmacol Rev 2022; 74:552-599. 3. Mills KA, Chess-Williams R, McDermott C. Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: Chloroacetaldehyde’s contribution to urothelial dysfunction in vitro. Arch Toxicol 2019; 93:3291-3303. 4. Gulcin İ. Anti-oxidants and anti-oxidant methods: An updated overview. Arch Toxicol 2020; 94:651-715. 5. Taslimi P, Kandemir FM, Demir Y, İleritürk M, Temel Y, Caglayan C, Gulçin İ. The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide-induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities. J Biochem Mol Toxicol 2019; 33:e22313. 6. Galal SM, Mansour HH, Elkhoely AA. Diallyl sulfide alleviates cyclophosphamide-induced nephropathic encephalopathy in rats. Toxicol Mech Methods 2020; 30:208-218. 7. Dhanisha SS, Drishya S, Guruvayoorappan C. Pithecellobium dulce fruit extract mitigates cyclophosphamide-mediated toxicity by regulating proinflammatory cytokines. J Food Biochem 2020; 44:e13083. 8. Alshahrani S, Ali Thubab HM, Ali Zaeri AM, Anwer T, Ahmed RA, Jali AM, et al. The protective effects of sesamin against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammatory-cytokines and apoptosis in rats. Int J Mol Sci 2022; 23:11615-11624. 9. Nićiforović N, Abramovič H. Sinapic acid and its derivatives: Natural sources and bioactivity. Compr Rev Food Sci Food Saf 2014; 13:34-51. 10. Pandi A, Kalappan VM. Pharmacological and therapeutic applications of sinapic acid—An updated review. Molecular biology reports 2021; 48:3733-3745. 11. Hu X, Geetha RV, Surapaneni KM, Veeraraghavan VP, Chinnathambi A, Alahmadi TA, et al. Lung cancer induced by Benzo(A)Pyrene: ChemoProtective effect of sinapic acid in swiss albino mice. Saudi J Biol Sci 2021; 28:7125-7133. 12. Ahmad A, Alkharfy KM, Bin Jardan YA, Shahid M, Ansari MA, Alqahtani S, et al. Sinapic acid mitigates methotrexate-induced hepatic injuries in rats through modulation of Nrf-2/HO-1 signaling. Environ Toxicol 2021; 36:1261-1268. 13. Ansari MA. Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomed Pharmacother 2017; 93:646-653. 14. Rezaei S, Hosseinimehr SJ, Zargari M, Karimpour Malekshah A, Mirzaei M, Talebpour Amiri F. Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress, caspase-3 and NF-kB activity in BALB/c mice. Andrologia 2021; 53:e14196. 15. Taghizadeh F, Hosseinimehr SJ, Zargari M, Karimpour Malekshah A, Talebpour Amiri FB. Gliclazide attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and caspase-3 activity. IUBMB Life 2020; 72:2024-2033. 16. Altındağ F, Ergen H. Sinapic acid alleviates cisplatin-induced acute kidney injury by mitigating oxidative stress and apoptosis. Environ Sci Pollut Res Int 2023; 30:12402-12411. 17. Ansari MA, Raish M, Ahmad A, Alkharfy KM, Ahmad SF, Attia SM, et al. Sinapic acid ameliorate cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-κB downregulation. Environ Toxicol Pharmacol 2017; 51:100-107. 18. Ansari MA, Raish M, Ahmad A, Ahmad SF, Mudassar S, Mohsin K, et al. Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats. Life Sci 2016; 165:1-8. 19. Şimşek H, Küçükler S, Gür C, Akaras N, Kandemir FM. Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: A multi-biomarker approach. Environ Sci Pollut Res Int 2023; 30:101208-101222. 20. Ahmad Ansari M, Shahid M, Ahmad SF, Ahmad A, Alanazi A, Malik A, et al. Sinapic acid alleviates 5-fluorouracil-induced nephrotoxicity in rats via Nrf2/HO-1 signalling. Saudi Pharm J 2023; 31:1351-1359. 21. Said E, Elkashef WF, Abdelaziz RR. Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity. Can J Physiol Pharmacol 2016; 94:347-358. 22. Sinanoglu O, Yener AN, Ekici S, Midi A, Aksungar FB. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urology 2012; 80:1392.e1391-1396. 23. Lin X, Yang F, Huang J, Jiang S, Tang Y, Li J. Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the NLRP3 pathway. Life Sci 2020; 256:117901. 24. Alaofi AL. Sinapic acid ameliorates the progression of streptozotocin (STZ)-induced diabetic nephropathy in rats via NRF2/HO-1 mediated pathways. Front Pharmacol 2020; 11:1119-1129. 25. Singh HP, Singh TG, Singh R. Sinapic acid attenuates cisplatin-induced nephrotoxicity through peroxisome proliferator-activated receptor gamma agonism in rats. J Pharm Bioallied Sci 2020; 12:146-154. 26. 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:e00659. 27. Caglayan C, Temel Y, Kandemir FM, Yildirim S, Kucukler S. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res Int 2018; 25:20968-20984. 28. Ansari MA, Raish M, Ahmad A, Alkharfy KM, Ahmad SF, Attia SM, et al. Sinapic acid ameliorate cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-κB downregulation. Environ Toxicol Pharmacol 2017; 51:100-107. 29. Ghareeb MA, Sobeh M, El-Maadawy WH, Mohammed HS, Khalil H, Botros S, Wink M. Chemical profiling of polyphenolics in eucalyptus globulus and evaluation of its hepato-renal protective potential against cyclophosphamide induced toxicity in mice. Antioxidants (Basel) 2019; 8:415-433. 30. HAS AL, Alotaibi MF, Bin-Jumah M, Elgebaly H, Mahmoud AM. Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney. Biomed Pharmacother 2019; 111:676-685. | ||
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