Sinapic acid attenuates cyclophosphamide-induced liver toxicity in mice by modulating oxidative stress, NF-κB, and caspase-3

Document Type : Original Article

Authors

1 Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran

2 Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Biochemistry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Objective(s): Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties.
Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked.
Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. 
Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice. 

Keywords

References

1. Doustimotlagh AH, Kokhdan EP, Vakilpour H, Khalvati B, Barmak MJ, Sadeghi H, et al. Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats. Mol Biol Rep 2020:47;1-12.
2. Al-Amarat W, Abukhalil MH, Alruhaimi RS, Alqhtani HA, Aldawood N, Alfwuaires MA, et al. Upregulation of Nrf2/HO-1 signaling and attenuation of oxidative stress, inflammation, and cell death mediate the protective effect of apigenin against cyclophosphamide hepatotoxicity. Metabolites 2022;12:648-662.
3. Mostafa RE, Morsi AH, Asaad GF. Piracetam attenuates cyclophosphamide-induced hepatotoxicity in rats: Amelioration of necroptosis, pyroptosis and caspase-dependent apoptosis. Life Sci 2022:303;120671.
4. Jiang S, Zhang Z, Yu F, Zhang Z, Yang Z, Tang Y, et al. Ameliorative effect of low molecular weight peptides from the head of red shrimp (Solenocera crassicornis) against cyclophosphamide-induced hepatotoxicity in mice. J Funct Foods 2020; 72:104085-104095.
5. 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;23:11615-11625.
6. Hamzeh M, Hosseinimehr SJ, Khalatbary AR, Mohammadi HR, Dashti A, Amiri FT. Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model. Res Pharm Sci 2018;13:440-449.
7. Aladaileh SH, Abukhalil MH, Saghir SA, Hanieh H, Alfwuaires MA, Almaiman AA, et al. Galangin activates Nrf2 signaling and attenuates oxidative damage, inflammation, and apoptosis in a rat model of cyclophosphamide-induced hepatotoxicity. Biomolecules 2019;9:346-365. 
8. Temel Y, Kucukler S, Yıldırım 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 Schmiedebergs Arch Pharmacol 2020;393:325-337.
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. Mol Biol Rep 2021;48:3733-3745.
11. Yun K-J, Koh D-J, Kim S-H, Park SJ, Ryu JH, Kim D-G, et al. Anti-inflammatory effects of Sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor- κB inactivation. J Agric Food Chem 2008;56:10265-10272.
12. Roy SJ, Prince PSM. Protective effects of sinapic acid on cardiac hypertrophy, dyslipidaemia and altered electrocardiogram in isoproterenol-induced myocardial infarcted rats. Eur J Pharmacol 2013;699:213-218.
13. Pari L, Jalaludeen AM. Protective role of sinapic acid against arsenic–induced toxicity in rats. Chem Biol Interact 2011;194:40-47. 
14. Shin D-S, Kim KW, Chung HY, Yoon S, Moon J-O. Effect of sinapic acid against carbon tetrachloride-induced acute hepatic injury in rats. Arch Pharm Res 2013;36:626-633. 
15. Janakiraman K, Kathiresan S, Mariadoss AV. Influence of sinapic acid on induction of apoptosis in human laryngeal carcinoma cell line. Int J Modern Res Rev 2014;2:165-170. 
16. Hamzeh M, Hosseinimehr SJ, Karimpour A, Mohammadi HR, Khalatbary AR, Amiri FT. Cerium oxide nanoparticles protect cyclophosphamide-induced testicular toxicity in mice. Int J Prev Med 2019;10:5-14.
17. Mohammadian M, Mianabadi M, Zargari M, Karimpour A, Khalafi M, Amiri FT. Effects of olive oil supplementation on sodium arsenate-induced hepatotoxicity in mice. Int J Prev Med 2018;9:59-66 
18. Cansu DÜ, Öztaş E, Yilmaz E, Korkmaz C. Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease: Case-based review. Rheumatol Int 2019;39:377-385. 
19. Patwa J, Khan S, Jena G. Nicotinamide attenuates cyclophosphamide‐induced hepatotoxicity in SD rats by reducing oxidative stress and apoptosis. J Biochem Mol Toxicol 2020;34:e22558. 
20. Khordad E, Alipour F, Pourabbas M, Mansouri S, Salimnejad R. hepatoprotective impact of ghrelin against cyclophosphamide-induced toxicity in the male mice. Drug Res 2021;71:407-412. 
21. Nićiforović N, Polak T, Makuc D, Poklar Ulrih N, Abramovič H. A kinetic approach in the evaluation of radical-scavenging efficiency of sinapic acid and its derivatives. Molecules 2017;22:375-392. 
22. Ansari MA. Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomed Pharmacother 2017;93:646-653. 
23. Lee J-Y. Anti-inflammatory effects of sinapic acid on 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in mice. Arch Pharm Res 2018;41:243-250. 
24. Caglayan C. The effects of naringin on different cyclophosphamide-induced organ toxicities in rats: investigation of changes in some metabolic enzyme activities. Environ Sci Pollut Res Int 2019;26:26664-26673. 
25. Jiang X, Yang F, Zhao Q, Tian D, Tang Y. Protective effects of pentadecapeptide derived from Cyclaina sinensis against Cyclophosphamide-induced hepatotoxicity. Biochem Biophys Res Commun 2019;520:392-398. 
26. 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. 
27. Arab-Nozari M, Ahangar N, Mohammadi E, Lorigooini Z, Shokrzadeh M, Amiri FT, et al. Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats. Mol Biol Rep 2020;47:6961-6972. 
28. Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI, et al. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-κB-mediated pathway. BioMed research international 2020:2020;1-20.
29. 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. 
30. 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. 
31. Jeon J, Sung J, Lee H, Kim Y, Jeong HS, Lee J. Protective activity of caffeic acid and sinapic acid against uvb‐induced photoaging in human fibroblasts. J Food Biochem 2019;43:e12701. 
32. Raish M, Shahid M, Bin Jardan YA, Ansari MA, Alkharfy KM, Ahad A, et al. Gastroprotective effect of sinapic acid on ethanol-induced gastric ulcers in rats: Involvement of Nrf2/ HO-1 and NF-κB signaling and antiapoptotic role. Front Pharmacol 2021;12:101-115. 
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 5
May 2023
Pages 526-531

Files

Share

How to cite

Statistics