Blood and biochemical changes caused by bee venom-nanoemulsions; a study on animal arthritis model

Document Type : Research Paper

Authors

1 Department of Medical Biotechnology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

2 Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University, Torbat Heydariyeh, Iran

3 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

4 Khalil Abad Health Center, Mashhad University of Medical Sciences, Mashhad, Iran

5 Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran

6 Radiation Biology Research Center Iran University of Medical Sciences (IUMS) Tehran, Iran

7 Stem Cells and Regenerative Medicine Innovation Center, Kerman University of Medical Sciences, Kerman, Iran

8 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Objective(s): Traditionally, Bee venom (BV) is used through stinging or injection to treat rheumatoid arthritis (RA). This study aimed to assess the side effects of local bee venom nanoemulsions (BV-NEs) in the collagen-induced arthritis (CIA) model by examining biochemical and hematological parameters. 
Materials and Methods: The BV-NEs were prepared, and the CIA model was induced in rats. After the seventh day, the groups were locally treated for two weeks as the following: blank (free treatment), negative control (NE-0), positive control (hydrocortisone acetate ointment 1%, 50 mg/day), BV control (37.5 µg/ml/day), and BV-NEs receiving 75, 37.5, 18.75, and 9.37 µg/ml/day. Three steps of blood sampling were done on days 0, 7, and 21 (healthy rats, before treatment, and at the end of treatment, respectively).
Results: The results revealed that blood levels of Glucose, Cholesterol, Urea, Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), White blood cell (WBC), and %Neutrophil significantly increased before the treatment. Nevertheless, most parameters declined at the end of the treatment compared to the blank and negative control groups about BV-NEs dose-dependently. The drastic changes in biochemical parameters in the CIA model indicated the effect of the immune system function on the metabolic system. Also, NE’s impact of BV passed through the skin on these items. 
Conclusion: BV-NEs can reduce inflammation caused by arthritis without acute adverse effects on the routine biochemical and hematological parameters.

Keywords


1. Yousefpoor Y, Bolouri B, Bayati M, Shakeri A, Eskandari Y. The combined effects of Aloe vera gel and silver nanoparticles on wound healing in rats. Nanomed J. 2016; 3(1): 57-64.
2. Yousefpoor Y, Esnaashari SS, Baharifar H, Mehrabi M, Amani A. Current challenges ahead in preparation, characterization, and pharmaceutical applications of nanoemulsions. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023: e1920.
3. Valizadeh A, Shirzad M, Pourmand MR, Farahmandfar M, Sereshti H, Amani A. Levofloxacin nanoemulsion gel has a powerful healing effect on infected wound in streptozotocin-induced diabetic rats. Drug Deliv Transl Res. 2021; 11(1): 292-304.
4. Maleki H, Azadi H, Yousefpoor Y, Doostan M, Doostan M, Farzaei MH. Encapsulation of Ginger Extract in Nanoemulsions: Preparation, Characterization and in vivo Evaluation in Rheumatoid Arthritis. J Pharm Sci. 2023; 112(6): 1687-1697.
5. Ghoryani M, Shariati-Sarabi Z, Tavakkol-Afshari J, Ghasemi A, Poursamimi J, Mohammadi M. Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: a successful clinical trial in Iran. Biomed Pharmacother. 2019; 109: 1834-1840.
6. Billiau A, Matthys P. Collagen-induced arthritis and related animal models: how much of their pathogenesis is auto-immune, how much is auto-inflammatory? Cytokine Growth Factor Rev. 2011; 22(5-6): 339-344.
7. Yousefpoor Y, Osanloo M, Mirzaei-Parsa MJ, Najafabadi MRH, Hashemi SM, Abbasifard M. Subcutaneous Injection of Bee Venom in Wistar Rats: effects on blood cells and biochemical parameters. JoP. 2022; 25(3): 250.
8. Yousefpoor Y, Amani A, Divsalar A, Mousavi SE, Torbaghan YE, Emami O. Assessment of hemolytic activity of bee venom against some physicochemical factors. J Asia Pac Entomol. 2019; 22(4): 1129-1135.
9. Lee J-D, Park H-J, Chae Y, Lim S. An overview of bee venom acupuncture in the treatment of arthritis. eCAM. 2005; 2.
10. Yousefpoor Y, Amani A, Divsalar A, Vafadar MR. Topical delivery of bee venom through the skin by a water-in-oil nanoemulsion. Nanomed J. 2022; 9(2): 131-137.
11. Abbasifard M, Yousefpoor Y, Amani A, Arababadi MK. Topical Bee Venom Nano-emulsion Ameliorates Serum Level of Endothelin-1 in Collagen-Induced Rheumatoid Arthritis Model. Bionanoscience. 2021: 1-6.
12. Hanafi MY, Zaher EL, El‑Adely SE, Sakr A, Ghobashi AH, Hemly MH, et al. The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD‑induced non‑alcoholic fatty liver in rats. Exp Ther Med. 2018; 15(6): 5091-5099.
13. Daher EDF, Silva Junior GBd, Bezerra GP, Pontes LB, Martins AMC, Guimarães JA. Acute renal failure after massive honeybee stings. Rev Inst Med Trop Sao Paulo. 2003; 45: 45-50.
14. Yousefpoor Y, Amani A, Divsalar A, Mousavi SE, Shakeri A, Sabzevari JT. Anti-rheumatic activity of topical nanoemulsion containing bee venom in rats. Eur. J. Pharm. Biopharm. 2022; 172: 168-176.
15. Darwish SF, El-Bakly WM, Arafa HM, El-Demerdash E. Targeting TNF-α and NF-κB activation by bee venom: role in suppressing adjuvant induced arthritis and methotrexate hepatotoxicity in rats. PLoS One. 2013; 8(11): e79284.
16. Zhang J-M, An J. Cytokines, inflammation and pain. Int. Anesthesiol. Clin. 2007; 45(2): 27.
17. Souto A, Salgado E, Maneiro JR, Mera A, Carmona L, Gómez‐Reino JJ. Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta‐analysis. A&R. 2015; 67(1): 117-127.
18. Mohammed ZI, Hassan AJ, editors. Effect of bee venom on some blood and biochemical parameters in formaldehyde induced arthritis male rats in comparison with prednisolone drug. J Phys Conf Ser. 2019: IOP Publishing.
19. Khulan T, Ambaga M, Chimedragcha C. Effect of Honey Bee Venom (Apis mellifera) on Hyperglycemia and Hyperlipidemia in Alloxan Induced Diabetic Rabbits. Diabetes Metab J. 2015; 6(3):1.66-0.07.
20. Zarrinnahad H, Mahmoodzadeh A, Hamidi MP, Mahdavi M, Moradi A, Bagheri KP, et al. Apoptotic effect of melittin purified from Iranian honey bee venom on human cervical cancer HeLa cell line. Int J Pept Res Ther. 2018;24(4):563-570.
21. Gawad SA, Fikry H, Amin MM, Elmahdi AR, Elaziz D. Effect of apitherapy on the pancreas and liver of streptozotacin induced diabetic rats: a biochemical and histological study. EJPMR. 2016;3:555-565.
22. Rodriguez-Acosta A, Vega J, Finol H, Pulido-Mendez M. Ultrastructural alterations in cortex of adrenal gland caused by the toxic effect of bee (Apis mellifera) venom. J Submicrosc Cytol Pathol. 2003;35(3):309-314.
23. Mousavi SM, Imani S, Haghighi S, Mousavi SE, Karimi A. Effect of Iranian honey bee (Apis mellifera) venom on blood glucose and insulin in diabetic rats. J Arthropod Borne Dis. 2012;6(2):136.
24. Alqutub AN, Masoodi I, Alsayari K, Alomair A. Bee sting therapy-induced hepatotoxicity: A case report. World . Hepatol. 2011;3(10):268.
25. Pu N, Gao S, Xu Y, Zhao G, Lv Y, Nuerxiati A, et al. Alkaline phosphatase-to-albumin ratio as a prognostic indicator in pancreatic ductal adenocarcinoma after curative resection. J Cancer. 2017;8(16):3362.
26. Fiț N, Chirilă F, Răpuntean S, Nadăș G, Preoteasa L, Cumpănașu F. Haematological and biochemical investigations in rats with rheumatoid arthritis induced by Freund Complete Adjuvant and treated with bee venom. Bull Univ Agric Sci Vet Med Cluj Napoca. 2011; 68(1):151-158.
27. Kang HS, Kim SJ, Lee MY, Jeon SH, Kim SZ, Kim JS. The cardiovascular depression caused by bee venom in Sprague-Dawley rats associated with a decrease of developed pressure in the left ventricular and the ratio of ionized calcium/ionized magnesium. Am J Chin Med. 2008;36(3):505-516.
28. Permyakov EA, Grishchenko VM, Kalinichenko LP, Orlov NY, Kuwajima K, Sugai S. Calcium-regulated interactions of human alpha-lactalbumin with bee venom melittin. Biophys. Chem. 1991;39(2):111-117.
29. Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-
releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol. Ther. 2007;115(2): 246-270.
30. Pamuk GE, Vural Ö, Turgut B, Demır M, Pamuk ÖN, Çakir N. Increased platelet activation markers in rheumatoid arthritis: are they related with subclinical atherosclerosis? Platelets. 2008; 19(2):146-54.