Cardioprotective effect of royal jelly on paclitaxel-induced cardio-toxicity in rats

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Urmia, Iran

3 Department of Pathology, Faculty of Veterinary Medicine, University of Urmia, Iran

4 Department of Clinical Pathology, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran

Abstract

Objective(s):Paclitaxel is a potent chemotherapy agent with severe side effects, including allergic reactions, cardiovascular problems, complete hair loss, joint and muscle pain, which may limit its use and lower its efficiency. The cardioprotective effect of royal jelly was investigated on paclitaxel-induced damages.
Materials and Methods:Adult male Wistar rats were divided into control and test groups (n=8). The test group was assigned into five subgroups; 4 groups, along with paclitaxel administration (7.5 mg/kg BW, weekly), received various doses of royal jelly (50, 100, and 150 mg/kg BW) for 28 consecutive days. The last group received only royal jelly at 100 mg/kg. In addition to oxidative and nitrosative stress biomarkers, the creatine kinase (CK-BM) level was also determined. To show the cardioprotective effect of royal jelly on paclitaxel-induced damages, histopathological examinations were conducted.
Results:Royal jelly lowered the paclitaxel-elevated malondialdehyde and nitric oxide levels in the heart. Royal jelly could also remarkably reduce the paclitaxel-induced cardiac biomarker of creatine kinase (CK-BM) level and pathological injuries such as diffused edema, hemorrhage, congestion, hyaline exudates, and necrosis. Moreover, royal jelly administration in a dose-dependent manner resulted in a significant (P<0.05) increase in the paclitaxel-reduced total antioxidant capacity.
Conclusion:Our data suggest that the paclitaxel-induced histopathological and biochemical alterations could be protected by the royal jelly administration. The cardioprotective effect of royal jelly may be related to the suppression of oxidative and nitrosative stress.

Keywords


1. Rowinsky EK, Donehower RC. The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol Ther 1991; 52:35-84.
2. Needleman DJ, Ojeda-Lopez MA, Raviv U, Ewert K, Miller HP, Wilson L, et al. Radial compression of microtubules and the mechanism of action of taxol and associated proteins. Biophys J 2005; 89:3410–3423.
3. Onetto N, Canetta R, Winograd B, Catane R, Dougan M, Grechko J, et al. Overview of Taxol safety. J Natl Cancer Inst Monogr 1993; 15:131–139.
4. Nagai T, Inoue R. Preparation and functional properties of water extract and alkaline extract of royal jelly. Food Chem 2004; 84:181–186.
5. Caparica-Santos C, Marcucci MC. Quantitative determination of trans-10- hydroxy-2-decenoic acid (10-HDA) in Brazilian royal jelly and commercial products containing royal jelly. J Apicultural Res 2007; 46:149–153.
6. Matsui T, Doi YA, Sugimoto S, Yamada H, Matsumoto HK. Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR. J Nutr Biochem 2002; 13:80–86.
7. Zhang K, Heidrich FM, De Gray B, Boehmerle W, Ehrlich BE. Paclitaxel accelerates spontaneous calcium oscillations in cardiomyocytes by interacting with NCS-1 and the InsP3R. J Mol Cell Cardiol 2010; 49:829–835.
8. Silici S, Ekmekcioglu O, Ersalan G, Demirtas S. Antioxidative effect of royal jelly in cisplatin-induced testes damage. J Urol 2009; 74:545-551.
9. Benzie IF, Strain JJ. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Meth Enzymol 1999; 299:15-27.
10. Apple FS, Murakami MM. Cardiac troponin and creatine kinase MB monitoring during in-hospital myocardial reinfarction. Clin Chem 2005; 51:460-463.
11. Niehaus WG, Samuelsson JRB. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6:126–130.
12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265–275.
13. Green LC, Wagne, AD, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982; 12:131-138.
14. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem: Anticancer Agents 2002; 2:1-17.
15. Lin HL, Liu TU, Chau GY, Lui WY,  Chi CW. Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species. Cancer 2000; 89:983-994.
16. Ramanathan B, Jan K, Chen C, Hour T, Yu H, Pu Y. Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res 2005; 65:8455-8460.
17. Schafer FQ, Qian SY, Buettner GR. Iron and free radical oxidations in cell membranes. Cell Mol Biol 2000; 46:657–662.
18. Kanbur M, Erasian G, Beyaz L, Silici S, Liman BC, Altinordulu S, et al. The effects of royal jelly on liver damage induced by paracetamol in mice. Exp Toxicol Pathol 2009; 61:123-132.
19. Azab KS, Bashandy M, Salem M, Ahmed O, Tawfik Z, Helal H. Royal jelly modulates oxidative stress and tissue injury in gamma irradiated male Wister Albino rats. N Am J Med Sci 2011; 3: 268–276.
20. Borges F, Fernandes E, Roleira F. Progress Towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 2002; 9:195–217.
21. Maguire JJ, Wilson DS, Packer L. Mitochondrial electron transport-linked tocopheroxyl radical reduction. J Biol Chem 1989; 264:21462–21465.
22. Mellio E, Chinou I. Chemistry and bioactivity of royal jelly from Greece. J Agric Food Chem 2005; 53:8987-8992.
23. Moradi AR, Malekinejad H, Farrokhi-Ardabili F, Bernousi I. Royal Jelly improves the sperm parameters of ram semen during liquid storage and serves as an antioxidant source. Small Rumin Res 2013; 113:346-352.
24. Delkhoshe-Kasmaie F, Malekinejad H, Khoramjouy M, Rezaei-Golmisheh A, Janbaze-Acyabar H. Royal jelly protects from taxol-induced testicular damages via improvement of antioxidant status and up-regulation of E2f1. Syst Biol Reprod Med 2014; 60:80-88.
25. Ferrari CKB. Oxidative stress pathophysiology: Searching for an effective antioxidant protection. Int Med J 2001; 8:175-184.
26. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993; 84:407-412.
27. Wang YF, Chen CY, Chung SF, Chiou YH, Lo HR.  Involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells. Cancer Chemother Pharmacol 2004; 54:322-330.
28. Sherif Y, Saad Tawfeeg A, Najjar O, Alashari M. Cardiotoxicity of doxorubicin/paclitaxel combination in rats: effect of sequence and timing of administration. J Biochem Mol Toxicol 2004; 18:78-86.
29. Andreadou I, Sigala F, Iliodromitis EK, Papaefthimiou M, Sigalas C, Aligiannis N, et al. Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. J Mol Cell Cardiol 2007; 42:549–558.