Investigation of the Effects of Hesperidin on Bisphenol-A Induced Neurotoxicity in Rats

Yıl 2024, Cilt: 19 Sayı: 1, 17 - 24, 26.04.2024

Merve Bolat Burak Batuhan Laçin , Fikret Çelebi

https://doi.org/10.17094/vetsci.1471518

Öz

Bisphenol A (BPA) is an adhesive substance used in the production of food packaging, electronic devices, dental sealants and polycarbonate plastics. This substance, which can leak into products during industrial processes, can be taken into the body through contact or consumption. BPA causes oxidative damage in the body and toxicity to organs. This study was conducted on 52 male rats. The rats were randomly distributed into 4 separate groups, with 13 animals in each. Experiment groups were formed as follows: Control: 1 ml of olive oil was administered intragastrically for 14 days. Hesperidin (HESP): HESP was administered intragastrically at a dose of 50 mg/kg for 14 days. BPA: BPA dissolved in olive oil was administered intragastrically at a dose of 100 mg/kg for 14 days. BPA+HESP: BPA at a dose of 100 mg/kg and HESP at a dose of 50 mg/kg were administered intragastrically for 14 days. Brain tissue samples from the rats were collected on the 15th day of the experiment while the rats were under sevoflurane anesthesia. Histopathological and biochemical analyzes were performed on the brain tissues of the rats. As a result of the study, it was observed that HESP had a protective effect on BPA-induced neurotoxicity in rats and triggered the antioxidant mechanism responsible for defense in the cell. It was opined that the degenerative and necrotic tissue damage caused by BPA in the brain tissue decreased with the effect of Hesperidin.

Anahtar Kelimeler

Bisphenol A, hesperidin, malondialdehyde, neurotoxicity, rat

Ratlarda Bisfenol-A’nın Neden Olduğu Nörotoksisite Üzerine Hesperidinin Etkilerinin Araştırılması

Öz

Bisfenol A (BPA), gıda ambalajı, elektronik cihazlar, diş dolguları ve polikarbon plastiklerin üretiminde kullanılan yapışkan bir maddedir. Bu madde, endüstriyel işlemler sırasında ürünlere sızabilir ve temas veya tüketim yoluyla vücuda alınabilir. BPA, vücutta oksidatif hasara ve organlara toksisiteye neden olabilir. Bu çalışma, 52 erkek sıçan üzerinde gerçekleştirilmiştir. Sıçanlar, her birinde 13 hayvan bulunan 4 ayrı gruba rastgele dağıtılmıştır. Deney grupları şu şekilde oluşturuldu: Kontrol: 1 ml zeytinyağı, 14 gün boyunca intragastrik olarak uygulandı. BPA maruz kalan gruplara HESP dozunda 100 mg/kg intragastrik uygulama ile verildi. HESP: HESP, 50 mg/kg dozunda 14 gün boyunca intragastrik olarak uygulandı. BPA: BPA, zeytinyağında çözülmüş olarak 100 mg/kg dozunda 14 gün boyunca intragastrik olarak uygulandı. BPA+HESP: BPA, 100 mg/kg dozunda ve HESP, 50 mg/kg dozunda 14 gün boyunca intragastrik olarak uygulandı. Deneyin 15. gününde, sıçanlar sevofluran anestezisi altındayken sıçanlardan beyin dokusu örnekleri toplandı. Sıçanların beyin dokularında histopatolojik ve biyokimyasal analizler yapıldı. Çalışma sonucunda, HESP’nin BPA tarafından indüklenen nörotoksisite üzerinde koruyucu bir etkisi olduğu ve hücre savunmasından sorumlu antioksidan mekanizmayı tetiklediği gözlemlendi. BPA'nın beyin dokusunda neden olduğu dejeneratif ve nekrotik doku hasarının, HESP’nin etkisi ile azaldığı düşünülmüştür.

Anahtar Kelimeler

Bisphenol A, hesperidin, malondialdehit, nörotoksisite, rat

Kaynakça

• 1. Sharma V, Jain D, Rai AR, et al. Toxicological assessment and concentration analysis of Bisphenol A in food grade plastics: A systematic review. Mater Today Proc. 2023;95(1):18-25.
• 2. Liu X, Shi H, Xie B, Dionyesiu DD, Zhao Y. Microplastics as both a sink and a source of bisphenol A in the marine environment. Environ Sci Technol. 2019;53(17):10188-10196.
• 3. Adebesin TN, Lateef SA, Oloruntoba EO, Adejumo M. Occurrence of bisphenol A, nonylphenol, octylphenol and heavy metals in groundwater from selected communities in Ibadan, Nigeria. J Water Health. 2023;21(6):740-750.
• 4. Wang X, Nag R, Brunton NP et al. Human health risk assessment of bisphenol A (BPA) through meat products. Environ Res. 2022;213:113734.
• 5. Sadeghı AA. Immune Cell Counts, Plasma Immunoglobulin Contents and INF-γ Gene Expression in Rats Exposed to Bisphenol A. Kafkas Üniv Vet Fak Derg. 2016;22(5):717-722.
• 6. Akbulut C, Kizil C, Yön ND. Effects of low doses of bisphenol a on primordial germ cells in zebrafish (Danio rerio) embryos and larvae. Kafkas Univ Vet Fak Derg. 2013;19(4):647-653.
• 7. Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015;11(10):610-625.
• 8. Mikolajewska K, Stragierowicz J, Gromadzinska J. Bisphenol A - application, sources of exposure and potential risks in infants, children and pregnant women. Int J Occup Med Environ Health. 2015;28(2): 209-241.
• 9. Ugboka UG, Ihedioha JN, Ekere NR, Okechukwu FO. Human health risk assessment of bisphenol A released from polycarbonate drinking water bottles and carbonated drinks exposed to sunlight in Nigeria. Int J Environ Anal Chem. 2022;102(12):2830-2840.
• 10. Wang H, Chang L, Aguilar JS, Dong S, Hong Y. Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells. Environ Int. 2019;127:324-332.
• 11. Balci A, Ozkemahli G, Erkekoglu P, Zeybek ND, Yersal N, Kocer-Gumusel B. Histopathologic, apoptotic and autophagic, effects of prenatal bisphenol A and/or di (2-ethylhexyl) phthalate exposure on prepubertal rat testis. Environ Sci Pollut Res. 2020;27(16):20104-20116.
• 12. Bilal M, Iqbal HM, Barceló D. Mitigation of bisphenol A using an array of laccase-based robust bio-catalytic cues–a review. Sci Total Environ. 2019;689(1):160-177.
• 13. Santoro A, Chianese R, Troisi J, et al. Neuro-toxic and reproductive effects of BPA. Curr Neuropharmacol. 2019;17(12):1109-1132.
• 14. Sahoo PK, Pradhan LK, Aparna S, Agarwal K, Banerjee A, Das SK. Quercetin abrogates bisphenol A induced altered neurobehavioral response and oxidative stress in zebrafish by modulating brain antioxidant defense system. Environ Toxicol Pharmacol. 2020;80:103483.
• 15. Ceylan H, Demir Y, Beydemir Ş. Inhibitory effects of usnic and carnosic acid on some metabolic enzymes: an in vitro study. Protein Pept Lett. 2019;26(5):364-370.
• 16. Naewla S, Sirichoat A, Pannangrong W, Chaisawang P, Wigmore P, Welbat JU. Hesperidin alleviates methotrexate-induced memory deficits via hippocampal neurogenesis in adult rats. Nutrients. 2019;11:936.
• 17. Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iransıhahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 2015;29(3):323-331.
• 18. Belhan S, Özkaraca M, Kandemir FM, et al. Effectiveness of Hesperidin on methotrexate-induced testicular toxicity in rats. Kafkas Üniv Vet Fak Derg. 2017;23(5):789-796.
• 19. Cenesiz S. The role of oxidant and antioxidant parameters in the infectious diseases: A systematic literature review. Kafkas Üniv Vet Fak Derg. 2020;26(6):849-858.
• 20. Dağlıoğlu YK, Acıpayam C, Benc IG, Kibar F, Koksal F. The effectiveness of Hesperidin in the prevention of bacterial translocation caused by methotrexate in the Gastrointestinal tract. Kafkas Üniv Vet Fak Derg. 2013;19(6):985-988.
• 21. Kaya K, Çiftçi O, Çetin A, Doğan H, Başak N. Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia. 2015;47(7):793-800.
• 22. Tekin S, Çelebi F. Investigation of the effect of Hesperidin on some reproductive parameters in testicular toxicity induced by Bisphenol A. Andrologia. 2022;54(10): e14562.
• 23. Güleş Ö, Kum Ş, Yıldız M, et al. Protective effect of coenzyme Q10 against bisphenol-A-induced toxicity in the rat testes. Toxicol Ind Health. 2019;35(7):466-481.
• 24. Amjad S, Rahman MS, Pang MG. Role of antioxidants in alleviating Bisphenol A toxicity. Biomolecules. 2020; 10(8):1105.
• 25. Kobroob A, Peerapanyasut W, Chattipakorn N, Wongmeikat O. Damaging Effects of Bisphenol A on the Kidney and the Protection by Melatonin: Emerging Evidences from In Vivo and In Vitro Studies. Oxid Med Cell Longev. 2018;18:3082438.
• 26. Mączka W, Grabarczyk M, Wińska KC. Can antioxidants reduce the toxicity of Bisphenol ?. Antioxidants (Basel). 2022;11(2):413.
• 27. Hassan ZK, Elobeid MA, Virk P, et al. Bisphenol A induces hepatotoxicity through oxidative stress in rat model. Oxid Med Cell Longev. 2012;194829.
• 28. Ishtiaq A, Ali T, Bakhtiar A, et al. Melatonin abated Bisphenol A induced neurotoxicity via p53/PUMA/Drp-1 signaling. Environ Sci Pollut Res Int. 2021;28(14):17789-17801.
• 29. Negri-Cesi P. Bisphenol A interaction with brain development and functions. Dose Response. 2015;13(2):1-12.
• 30. Gassman NR. Induction of oxidative stress by bisphenol A and its pleiotropic effects. Environ Mol Mutagen. 2017; 58(2):60-71.
• 31. Semis HS, Kandemir FM, Kaynar O, Dogan T, Arikan SM. The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats. Life Sci. 2021;287:120104.
• 32. Estruel Amades S, Massot Cladera M, Garcia Cerdà P, et al. Protective effect of hesperidin on the oxidative stress induced by an exhausting exercise in intensively trained rats. Nutrients. 2019;11(4):1-17.
• 33. Pari L, Karthikeyan A, Karthika P, Rathinam A. Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats. Toxicol Rep. 2015;7(2):46-55.
• 34. Hajialyani M, Hosein Farzaei M, Echeverría J, Nabavi SM, Uriarte E, Sobarzo-Sanchez E. Hesperidin as a neuroprotective agent: a review of animal and clinical evidence. Molecules. 2019;24(3): 1-18.
• 35. Welbat JU, Naewla S, Pannangrong W, Sirichoat A, Aranarochana A, Wigmore P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat. Biochem Pharmacol. 2020;178:114083.
• 36. Li X, Huang W, Tan R, et al. The benefits of hesperidin in central nervous system disorders, based on the neuroprotective effect. Biomed Pharmacother. 2023;159:114222.
• 37. Eid JI, Eissa SM, El-Ghor AA. Bisphenol A induces oxidative stress and DNA damage in hepatic tissue of female rat offspring. J Basic Appl Zool. 2015;71:10-19.
• 38. Mahmoudi A, Ghorbel H, Marrekchi R, Marreckhi R, Isoda H, Sayadi S. Oleropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups. Exp Toxicol Pathol. 2015; 67(7-8): 413-425.
• 39. Abdou HM, Abd Elkader, HTAE, El-Gendy AH, Ewada SM. Neurotoxicity and neuroinflammatory effects of bisphenol A in male rats: the neuroprotective role of grape seed proanthocyanidins. Environ Sci Pollut Res. 2021;(29):9257-9268.
• 40. El Morsy EM, Ahmed MAE. Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats. Hum Exp Toxicol. 2020;39(8): 1066-1078.
• 41. Welbat JU, Naewla S, Pannangrong W, Sirichoat A, Aranarochana A, Wigmore P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat. Biochem Pharmacol. 2020;178:114083.
• 42. Noshy PA, Azouz RA. Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats. Neurotoxicol Teratol. 2021;86:106981.
• 43. Hajialyani M, Hosein Farzaei M, Echeverría J, Nabavi SM, Uriarte E, Sobarzo-Sanchez E. Hesperidin as a neuroprotective agent: a review of animal and clinical evidence. Molecules. 2019;24(3): 648.
• 44. Kara A, Gedikli S, Sengul E, Gelen V, Ozkanlar S. Oxidative stress and autophagy. In: Ahmad R ed. Free Radicals and Diseases 1st edn. London: InTechOpen; 2016: 69-86.
• 45. Ishtiaq A, Ali T, Bakhtiar A, et al. Melatonin abated Bisphenol A induced neurotoxicity via p53/PUMA/Drp-1 signaling. Environ Sci Pollut Res Int. 2021;28(14):17789-17801.
• 46. Geetharathan, T. Effect of bisphenol-A on brain tissue in pregnant rat. Int J Curr Microbiol Appl Sci. 2016;5(8):677-689.
• 47. Ayazgök B, Tuylu Kucukkilinc Z. Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. Marmara Pharma J. 2019;23(3):354-359.
• 48. Li C, Zug C, Qu H, Schluesener H, Zhang Z. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice. Behav Brain Res. 2015;281:32-42.