The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD‑induced non‑alcoholic fatty liver in rats

Hanafi,Mervat Y.; Zaher,Eman L.M.; El‑Adely,Soha E.M.; Sakr,Ahmed; Ghobashi,Ahmed H.M.; Hemly,Madiha H.; Kazem,Amani H.; Kamel,Maher A.

doi:10.3892/etm.2018.6028

The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD‑induced non‑alcoholic fatty liver in rats

Authors:
- Mervat Y. Hanafi
- Eman L.M. Zaher
- Soha E.M. El‑Adely
- Ahmed Sakr
- Ahmed H.M. Ghobashi
- Madiha H. Hemly
- Amani H. Kazem
- Maher A. Kamel
View Affiliations

Affiliations: Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt, Department of Pharmacology, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt, Department of Genetics, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt, Department of Pathology, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt
Published online on: April 3, 2018 https://doi.org/10.3892/etm.2018.6028
Pages: 5091-5099

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study was designed to investigate the therapeutic effects of bee venom (BV) on high‑fat diet (HFD)‑induced non‑alcoholic fatty liver (NAFL) in rats at different levels. Histological manifestations, hepatic lipid content, liver function tests, glucose homeostasis, lipid abnormalities, adipocytokines, lipid peroxidation, disturbed glutathione and antioxidant enzymes systems and dysregulation of Nrf2 transcription factor were assessed. In the present study, the NAFL rats were subcutaneously treated with BV with different doses (0.01, 0.05, 0.1 mg/kg). The results indicated that BV treatment completely normalized the lipid profile values of NAFL rats. Fasting blood sugar, insulin level and homeostatic model assessment of insulin resistance significantly decreased. BV treated rats showed a significantly lower level of all liver enzymes and bilirubin. Moreover, BV treatment significantly increased the levels of active nuclear erythroid factor 2 like 2, glutathione (GSH) (total and reduced), GSH/glutathione disulphide ratio and activities of glutathione reductase, glutathione‑S‑transferase and glutathione peroxidase (total and Se‑dependent). The level of tumor necrosis factor‑α was reduced. Treatment showed correction of adiponectin level, and significant downregulation of hepatic triglycerides and cholesterol. At the histological level, BV improved the architecture of liver cells showing normal sinusoids. It may be concluded that BV may represent an interesting therapeutic alternative for the treatment of NAFL disease.

View Figures

View References

1	Neuschwander-Tetri BA and Caldwell SH: Nonalcoholic steatohepatitis: Summary of an AASLD single topic conference. Hepatology. 37:1202–1219. 2003. View Article : Google Scholar : PubMed/NCBI
2	Musso G, Cassader M, De Michieli F, Rosina F, Orlandi F and Gambino R: Nonalcoholic steatohepatitis versus steatosis: Adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism. Hepatology. 56:933–942. 2012. View Article : Google Scholar : PubMed/NCBI
3	Halbleib M, Skurk T, de Luca C, von Heimburg D and Hauner H: Tissue engineering of white adipose tissue using hyaluronic acid-based scaffolds. I: In vitro differentiation of human adipocyte precursor cells on scaffolds. Biomaterials. 24:3125–3132. 2003. View Article : Google Scholar : PubMed/NCBI
4	Day CP and James OF: Steatohepatitis: A tale of two ‘hits’? Gastroenterology. 114:842–845. 1998. View Article : Google Scholar : PubMed/NCBI
5	Bugianesi E, Gastaldelli A, Vanni E, Gambino R, Cassader M, Baldi S, Ponti V, Pagano G, Ferrannini E and Rizzetto M: Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: Sites and mechanisms. Diabetologia. 48:634–642. 2005. View Article : Google Scholar : PubMed/NCBI
6	Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A and George J: Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology. 40:46–54. 2004. View Article : Google Scholar : PubMed/NCBI
7	Houstis N, Rosen ED and Lander ES: Reactive oxygen species have a casual role in multiple forms of insulin resistance. Nature. 440:944–948. 2006. View Article : Google Scholar : PubMed/NCBI
8	Franco R, Schoneveld OJ, Pappa A and Panayiotidis MI: The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem. 113:234–258. 2007. View Article : Google Scholar : PubMed/NCBI
9	Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M and Kensler TW: Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem. 278:8135–8145. 2003. View Article : Google Scholar : PubMed/NCBI
10	Yates MS, Tran QT, Dolan PM, Osburn WO, Shin S, McCulloch CC, Silkworth JB, Taguchi K, Yamamoto M, Williams CR, et al: Genetic versus chemoprotective activation of Nrf2 signaling: Overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis. 30:1024–1031. 2009. View Article : Google Scholar : PubMed/NCBI
11	Sugimoto H, Okada K, Shoda J, Warabi E, Ishige K, Ueda T, Taguchi K, Yanagawa T, Nakahara A, Hyodo I, et al: Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol. 298:G283–G294. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhang YK, Yeager RL, Tanaka Y and Klaassen CD: Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet. Toxicol Appl Pharmacol. 245:326–334. 2010. View Article : Google Scholar : PubMed/NCBI
13	Jang MH, Shin MC, Lim S, Han SM, Park HJ, Shin I, Lee JS, Kim KA, Kim EH and Kim CJ: Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. J Pharmacol Sci. 91:95–104. 2003. View Article : Google Scholar : PubMed/NCBI
14	Hong SJ, Rim GS, Yang HI, Yin CS, Koh HG, Jang MH, Kim CJ, Choe BK and Chung JH: Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis. Toxicon. 46:39–45. 2005. View Article : Google Scholar : PubMed/NCBI
15	Sene-Fiorese M, Duarte FO, Scarmagnani FR, Cheik NC, Manzoni MS, Nonaka KO, Rossi EA, de Oliveira Duarte AC and Dâmaso AR: Efficiency of intermittent exercise on adiposity and fatty liver in rats fed with high fat diet. Obesity (Silver Spring). 16:2217–2222. 2008. View Article : Google Scholar : PubMed/NCBI
16	Lopes-Virella MF, Stone PG and Colwell JA: Serum high density lipoprotein in diabetic patients. Diabetologia. 13:285–291. 1977. View Article : Google Scholar : PubMed/NCBI
17	Friedewald WT, Levy RI and Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 18:499–502. 1972.PubMed/NCBI
18	Caumo A, Perseghin G, Brunani A and Luzi L: New insights on the simultaneous assessment of insulin sensitivity and beta-cell function with the HOMA2 method. Diabetes Care. 29:2733–2734. 2006. View Article : Google Scholar : PubMed/NCBI
19	Bligh EG and Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 37:911–917. 1959. View Article : Google Scholar : PubMed/NCBI
20	Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L and Rajasekaran NS: Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med. 52:366–376. 2012. View Article : Google Scholar : PubMed/NCBI
21	Draper HH and Hadley M: Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 186:421–431. 1990. View Article : Google Scholar : PubMed/NCBI
22	Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem. 106:207–212. 1980. View Article : Google Scholar : PubMed/NCBI
23	Smith IK, Vierheller TL and Thorne CA: Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis(2-nitrobenzoic acid). Anal Biochem. 175:408–413. 1988. View Article : Google Scholar : PubMed/NCBI
24	Habig WH, Pabst MJ and Jakoby WB: Glutathione S-transferase AA from rat liver. Arch Biochem Biophys. 175:710–716. 1976. View Article : Google Scholar : PubMed/NCBI
25	Flohé L and Günzler WA: Assays of glutathione peroxidase. Methods Enzymol. 105:114–121. 1984. View Article : Google Scholar : PubMed/NCBI
26	Tangvarasittichai S: Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes. 6:456–480. 2015. View Article : Google Scholar : PubMed/NCBI
27	Di Chiara T, Argano C, Corrao S, Scaglione R and Licata G: Hypoadiponectinemia: A link between visceral obesity and metabolic syndrome. J Nutr Metab. 2012:1752452012. View Article : Google Scholar : PubMed/NCBI
28	Tilg H and Moschen AR: Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 6:772–783. 2006. View Article : Google Scholar : PubMed/NCBI
29	Tilg H and Hotamisligil GS: Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology. 131:934–945. 2006. View Article : Google Scholar : PubMed/NCBI
30	Kono H, Rusyn I, Yin M, Gäbele E, Yamashina S, Dikalova A, Kadiiska MB, Connor HD, Mason RP, Segal BH, et al: NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. J Clin Invest. 106:867–872. 2000. View Article : Google Scholar : PubMed/NCBI
31	Weltman MD, Farrell GC, Hall P, Ingelman-Sundberg M and Liddle C: Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology. 27:128–133. 1998. View Article : Google Scholar : PubMed/NCBI
32	Shoelson SE, Herrero L and Naaz A: Obesity, inflammation, and insulin resistance. Gastroenterology. 132:2169–2180. 2007. View Article : Google Scholar : PubMed/NCBI
33	Kensler TW, Wakabayashi N and Biswal S: Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 47:89–116. 2007. View Article : Google Scholar : PubMed/NCBI
34	Lee JY, Kang SS, Kim JH, Bae CS and Choi SH: Inhibitory effect of whole bee venom in adjuvant-induced arthritis. In Vivo. 19:801–805. 2005.PubMed/NCBI
35	Mousavi SM, Imani S, Haghighi S, Mousavi SE and Karimi A: Effect of Iranian honey bee (Apis mellifera) venom on blood glucose and insulin in diabetic rats. J Arthropod Borne Dis. 6:136–143. 2012.PubMed/NCBI
36	Behroozi J, Divsalar A and Saboury AA: Honey bee venom decreases the complications of diabetes by preventing hemoglobin glycation. J Molec Liquids. 199:371–375. 2014. View Article : Google Scholar
37	Yang EJ, Jiang JH, Lee SM, Yang SC, Hwang HS, Lee MS and Choi SM: Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. J Neuroinflammation. 7:692010. View Article : Google Scholar : PubMed/NCBI
38	Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M and Kensler TW: Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem. 278:8135–8145. 2003. View Article : Google Scholar : PubMed/NCBI
39	Mo C, Wang L, Zhang J, Numazawa S, Tang H, Tang X, Han X, Li J, Yang M, Wang Z, et al: The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxid Redox Signal. 20:574–588. 2014. View Article : Google Scholar : PubMed/NCBI
40	Joo MS, Kim WD, Lee KY, Kim JH, Koo JH and Kim SG: AMPK facilitates nuclear accumulation of Nrf2 by phosphorylating at serine 550. Mol Cell Biol. 36:1931–1942. 2016. View Article : Google Scholar : PubMed/NCBI
41	Hwang DS, Kim SK and Bae H: Therapeutic effects of bee venom on immunological and neurological diseases review. Toxins (Basel). 7:2413–2421. 2015. View Article : Google Scholar : PubMed/NCBI
42	Ram SKM, Jayapal N, Nanaiah P, Aswal GS, Ramnarayan BK and Taher SM: The therapeutic benefits of bee venom. Int J Curr Microbiol App Sci. 3:377–381. 2014.