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The Effects of Coenzyme Q10 on Bisphenol A-Induced Pancreatic Changes in RatsPP

Year 2020, , 335 - 341, 25.12.2020
https://doi.org/10.35440/hutfd.688689

Abstract

Background: In the study, it was aimed to determine the changes in the pancreas of rats exposed to bisphenol A (BPA) and to reveal the effects of coenzyme Q10 (CoQ10) on these changes.
Materials and Methods: The rats were randomly divided into five groups as follows: control, sham, CoQ10, BPA and CoQ10+BPA. The applications of CoQ10 and BPA continued for fourteen days. Crossmon’s triple staining method was applied to the pancreas sections for histopathological and histomorphological examinations. Also, estrogen receptor α (ERα) immunoreactivity on the pancreas tissue was examined immunohistochemically.
Results: It was determined that histopathological changes in the endocrine part of the pancreas and ERα immunoreactivity on the pancreatic beta cells significantly increased in BPA group compared to control group. But a significant difference wasn't found between the groups in terms of histomorphological findings. On the other hand, a significant effect of CoQ10 wasn’t observed on the parameters analyzed in the study.
Conclusion: BPA might cause structural and functional disorders in the pancreas. Also, it might change ERα immunoreactivity, too. However, further studies are required to reveal the possible protective effects of CoQ10 in the pancreas of rats exposed to BPA.

References

  • Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y, et al. Developmental effects of perinatal exposure to bisphenol A and diethylstilbestrol on reproductive organs in female mice. Reprod Toxicol. 2002;16(2):107-16.
  • Tan BL, Kassim NM, Mohd MA. Assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol A and nonylphenol. Toxicol Lett. 2003;143(3):261-70.
  • Markey CM, Michaelson CL, Veson EC, Sonnenschein C, Soto AM. The mouse uterotrophic assay: a reevaluation of its validity in assessing the estrogenicity of bisphenol A. Environ Health Perspect. 2001;109(1):55-60.
  • Song H, Zhang T, Yang P, Li M, Yang Y, Wang Y, et al. Low doses of bisphenol A stimulate the proliferation of breast cancer cells via ERK1/2/ERRγ signals. Toxicol In Vitro. 2015;30(1 Pt B):521-8.
  • Qiu LL, Wang X, Zhang XH, Zhang Z, Gu J, Liu L, et al. Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. Toxicol Lett. 2013;219(2):116-24.
  • Batista TM, Alonso-Magdalena P, Vieira E, Amaral ME, Cederroth CR, Nef S, et al. Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice. PLoS One. 2012;7(3):e33814.
  • Filiz AK. Pankreas Fizyolojisi. Türkiye Klinikleri J Gastroenterohepatol-Special Topics. 2017;10(3):122-5.
  • Adachi T, Yasuda K, Mori C, Yoshinaga M, Aoki N, Tsujimoto G, et al. Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors. Food Chem Toxicol. 2005;43(5):713-9.
  • Ding S, Fan Y, Zhao N, Yang H, Ye X, He D, et al. High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A. J Endocrinol. 2014;221(1): 167-79.
  • Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006;114(1):106-12.
  • Bodin J, Bølling AK, Samuelsen M, Becher R, Løvik M, Nygaard UC. Long-term bisphenol A exposure accelerates insulitis development in diabetes-prone NOD mice. Immunopharmacol Immunotoxicol. 2013;35(3):349-58.
  • Bodin J, Bølling AK, Becher R, Kuper F, Løvik M, Nygaard UC. Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice. Toxicol Sci. 2014;137(2):311-23.
  • Alonso-Magdalena P, García-Arévalo M, Quesada I, Nadal Á. Bisphenol-A treatment during pregnancy in mice: a new window of susceptibility for the development of diabetes in mothers later in life. Endocrinology. 2015;156(5):1659-70.
  • Weldingh NM, Jørgensen-Kaur L, Becher R, Holme JA, Bodin J, Nygaard UC, et al. Bisphenol A is more potent than phthalate metabolites in reducing pancreatic β-cell function. Biomed Res Int. 2017;2017:4614379.
  • Alonso-Magdalena P, Laribi O, Ropero AB, Fuentes E, Ripoll C, Soria B, et al. Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environ Health Perspect. 2005;113(8):969-77.
  • Whitehead R, Guan H, Arany E, Cernea M, Yang K. Prenatal exposure to bisphenol A alters mouse fetal pancreatic morphology and islet composition. Horm Mol Biol Clin Investig. 2016;25(3):171-9.
  • Ozaydın T, Oznurlu Y, Sur E, Celik I, Uluısık D, Dayan MO. Effects of bisphenol A on antioxidant system and lipid profile in rats. Biotech Histochem. 2018;93(4):231-8.
  • Nadal A, Alonso-Magdalena P, Soriano S, Ripoll C, Fuentes E, Quesada I, et al. Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells. Front Biosci. 2011;16:251-60.
  • Nadal A, Alonso-Magdalena P, Soriano S, Quesada I, Ropero AB. The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for bloodglucose homeostasis and diabetes. Mol Cell Endocrinol. 2009;304(1-2):63-8.
  • Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M, Gauthier BR, et al. Pancreatic insulin content regulation by the estrogen receptor ER alpha. PLoS One. 2008;3(4):e2069.
  • Kang HS, Yang H, Ahn C, Kang HY, Hong EJ, Jaung EB. Effects of xenoestrogens on streptozotocin-induced diabetic mice. J Physiol Pharmacol. 2014;65(2):273-82.
  • Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P. Coenzyme Q10 supplementation in aging and disease. Front Physiol. 2018;9:44.
  • Sun IL, Sun EE, Crane FL, Morré DJ. Evidence for coenzyme Q function in transplasma membrane electron transport. Biochem Biophys Res Commun. 1990;172(3):979-84.
  • Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011;3(3):466-7.
  • Sena CM, Nunes E, Gomes A, Santos MS, Proença T, Martins MI, et al. Supplementation of coenzyme Q10 and alpha tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats. Nutr Res. 2008;28(2):113-21.
  • Lorza-Gil E, de Souza JC, García-Arévalo M, Vettorazzi JF, Marques AC, Salerno AG, et al. Coenzyme Q10 protects against β-cell toxicity induced by pravastatin treatment of hypercholesterolemia. J Cell Physiol. 2019;234(7):11047-59.
  • Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi-Tabatabaee SA, et al. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxid Med Cell Longev. 2016;2016:5818479.
  • Modi KP, Vishwakarma SL, Goyal RK, Bhatt PA. Beneficial effects of coenzyme Q10 in streptozotocin-induced type I diabetic rats. Iranian Journal Of Pharmacology & Therapeutics. 2006;5:61-5.
  • Elbe H, Öztürk F, Taşlıdere E, Çetin A, Doğan Z, Avcı S, et al. Wistar albino sıçanlarda streptozotocin ile oluşan diyabetik pankreas hasarında caffeic acid phenethyl ester (CAPE)’in tedavi edici etkileri. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi. 2015;2(1):22-9.
  • Sandikci M, Karagenc L, Yildiz M. Changes in the pancreas in experimental diabetes and the effect of lycopene on these changes: Proliferating, apoptotic, and estrogen receptor α positive cells. Anat Rec. 2017;300(11):2000-07.
  • García-Arévalo M, Alonso-Magdalena P, Servitja JM, Boronat-Belda T, Merino B, Villar-Pazos S, et al. Maternal exposure to bisphenol-A during pregnancy increases pancreatic β cell growth during early life in male mice offspring. Endocrinology. 2016;157(11):4158-71.
  • Poormoosavi SM, Najafzadehvarzi H, Behmanesh MA, Amirgholami R. Protective effects of asparagus officinalis extract against bisphenol A-induced toxicity in wistar rats. Toxicol Rep. 2018;5:427-33.
  • Korkmaz A, Ahbab MA, Kolankaya D, Barlas N. Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food Chem Toxicol. 2010;48(10):2865-71.
  • Aydoğan M, Korkmaz A, Barlas N, Kolankaya D. The effect of vitamin C on bisphenol A, nonylphenol and octylphenol induced brain damages of male rats. Toxicology. 2008;249(1): 35-9.
  • Markey CM, Wadia PR, Rubin BS, Sonnenschein C, Soto AM. Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract. Biol Reprod. 2005;72(6):1344-51.
  • Ibrahim MA, Elbakry RH, Bayomy NA. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat. Int J Exp Pathol. 2016;97(1):27-36.
  • Takao T, Nanamiya W, Nazarloo HP, Matsumoto R, Asaba K, Hashimoto K. Exposure to the environmental estrogen bisphenol A differentially modulated estrogen receptor-alpha and -beta immunoreactivity and mRNA in male mouse testis. Life Sci. 2003;72(10):1159-69.
  • Ahmed RA, ElGhamrawy TA, Salama EE. Effect of prenatal exposure to bisphenol a on the vagina of albino rats: immunohistochemical and ultrastructural study. Folia Morphol. 2014;73(4):399-408.
  • Sun IO, Jin L, Jin J, Lim SW, Chung BH, Yang CW. The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus. Korean J Intern Med. 2019;34(2): 365-74.
  • Lopez-Moreno J, Quintana-Navarro GM, Delgado-Lista J, Garcia-Rios A, Alcala-Diaz JF, Gomez-Delgado F et al. Mediterranean diet supplemented with coenzyme Q10 modulates the postprandial metabolism of advanced glycation end products in elderly men and women. J Gerontol A Biol Sci Med Sci. 2018;73(3):340-6.

Sıçanlarda Bisfenol A’nın Neden Olduğu Pankreatik Değişimler Üzerine Koenzim Q10’un Etkileri

Year 2020, , 335 - 341, 25.12.2020
https://doi.org/10.35440/hutfd.688689

Abstract

Amaç: Çalışmada bisfenol A (BPA)'ya maruz bırakılan sıçanların pankreasındaki değişikliklerin belirlenmesi ve bu değişiklikler üzerine koenzim Q10 (KoQ10)'un etkilerinin ortaya çıkarılması amaçlandı.
Materyal ve metod: Sıçanlar kontrol, sham, KoQ10, BPA ve KoQ10+BPA olmak üzere rastgele beş gruba ayrıldı. KoQ10 ve BPA uygulamaları on dört gün boyunca devam etti. Histopatolojik ve histomorfolojik incelemeler için pankreas kesitlerine Crossmon’un üçlü boyama yöntemi uygulandı. Ayrıca pankreas dokusunda immünohistokimyasal olarak östrojen reseptör α (ERα) immünoreaktivitesi incelendi.
Bulgular: Pankreasın endokrin bölümündeki histopatolojik değişiklikler ile pankreatik beta hücrelerindeki ERα immünoreaktivitesinin kontrol grubuna göre BPA grubunda anlamlı bir şekilde arttığı tespit edildi. Ancak histomorfolojik bulgular açısından gruplar arasında anlamlı bir fark bulunmadı. Diğer taraftan, çalışmada incelenen parametreler üzerinde KoQ10'un anlamlı bir etkisi gözlenmedi.
Sonuç: BPA, pankreasta yapısal ve fonksiyonel bozukluklara neden olabilir. Ayrıca ERα immünoreaktivitesini de değiştirebilir. Bununla birlikte, KoQ10'un BPA'ya maruz kalan sıçanların pankreasındaki muhtemel koruyucu etkilerini ortaya çıkarmak için daha ileri çalışmalar gereklidir.

References

  • Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y, et al. Developmental effects of perinatal exposure to bisphenol A and diethylstilbestrol on reproductive organs in female mice. Reprod Toxicol. 2002;16(2):107-16.
  • Tan BL, Kassim NM, Mohd MA. Assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol A and nonylphenol. Toxicol Lett. 2003;143(3):261-70.
  • Markey CM, Michaelson CL, Veson EC, Sonnenschein C, Soto AM. The mouse uterotrophic assay: a reevaluation of its validity in assessing the estrogenicity of bisphenol A. Environ Health Perspect. 2001;109(1):55-60.
  • Song H, Zhang T, Yang P, Li M, Yang Y, Wang Y, et al. Low doses of bisphenol A stimulate the proliferation of breast cancer cells via ERK1/2/ERRγ signals. Toxicol In Vitro. 2015;30(1 Pt B):521-8.
  • Qiu LL, Wang X, Zhang XH, Zhang Z, Gu J, Liu L, et al. Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. Toxicol Lett. 2013;219(2):116-24.
  • Batista TM, Alonso-Magdalena P, Vieira E, Amaral ME, Cederroth CR, Nef S, et al. Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice. PLoS One. 2012;7(3):e33814.
  • Filiz AK. Pankreas Fizyolojisi. Türkiye Klinikleri J Gastroenterohepatol-Special Topics. 2017;10(3):122-5.
  • Adachi T, Yasuda K, Mori C, Yoshinaga M, Aoki N, Tsujimoto G, et al. Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors. Food Chem Toxicol. 2005;43(5):713-9.
  • Ding S, Fan Y, Zhao N, Yang H, Ye X, He D, et al. High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A. J Endocrinol. 2014;221(1): 167-79.
  • Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006;114(1):106-12.
  • Bodin J, Bølling AK, Samuelsen M, Becher R, Løvik M, Nygaard UC. Long-term bisphenol A exposure accelerates insulitis development in diabetes-prone NOD mice. Immunopharmacol Immunotoxicol. 2013;35(3):349-58.
  • Bodin J, Bølling AK, Becher R, Kuper F, Løvik M, Nygaard UC. Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice. Toxicol Sci. 2014;137(2):311-23.
  • Alonso-Magdalena P, García-Arévalo M, Quesada I, Nadal Á. Bisphenol-A treatment during pregnancy in mice: a new window of susceptibility for the development of diabetes in mothers later in life. Endocrinology. 2015;156(5):1659-70.
  • Weldingh NM, Jørgensen-Kaur L, Becher R, Holme JA, Bodin J, Nygaard UC, et al. Bisphenol A is more potent than phthalate metabolites in reducing pancreatic β-cell function. Biomed Res Int. 2017;2017:4614379.
  • Alonso-Magdalena P, Laribi O, Ropero AB, Fuentes E, Ripoll C, Soria B, et al. Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environ Health Perspect. 2005;113(8):969-77.
  • Whitehead R, Guan H, Arany E, Cernea M, Yang K. Prenatal exposure to bisphenol A alters mouse fetal pancreatic morphology and islet composition. Horm Mol Biol Clin Investig. 2016;25(3):171-9.
  • Ozaydın T, Oznurlu Y, Sur E, Celik I, Uluısık D, Dayan MO. Effects of bisphenol A on antioxidant system and lipid profile in rats. Biotech Histochem. 2018;93(4):231-8.
  • Nadal A, Alonso-Magdalena P, Soriano S, Ripoll C, Fuentes E, Quesada I, et al. Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells. Front Biosci. 2011;16:251-60.
  • Nadal A, Alonso-Magdalena P, Soriano S, Quesada I, Ropero AB. The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for bloodglucose homeostasis and diabetes. Mol Cell Endocrinol. 2009;304(1-2):63-8.
  • Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M, Gauthier BR, et al. Pancreatic insulin content regulation by the estrogen receptor ER alpha. PLoS One. 2008;3(4):e2069.
  • Kang HS, Yang H, Ahn C, Kang HY, Hong EJ, Jaung EB. Effects of xenoestrogens on streptozotocin-induced diabetic mice. J Physiol Pharmacol. 2014;65(2):273-82.
  • Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P. Coenzyme Q10 supplementation in aging and disease. Front Physiol. 2018;9:44.
  • Sun IL, Sun EE, Crane FL, Morré DJ. Evidence for coenzyme Q function in transplasma membrane electron transport. Biochem Biophys Res Commun. 1990;172(3):979-84.
  • Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011;3(3):466-7.
  • Sena CM, Nunes E, Gomes A, Santos MS, Proença T, Martins MI, et al. Supplementation of coenzyme Q10 and alpha tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats. Nutr Res. 2008;28(2):113-21.
  • Lorza-Gil E, de Souza JC, García-Arévalo M, Vettorazzi JF, Marques AC, Salerno AG, et al. Coenzyme Q10 protects against β-cell toxicity induced by pravastatin treatment of hypercholesterolemia. J Cell Physiol. 2019;234(7):11047-59.
  • Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi-Tabatabaee SA, et al. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxid Med Cell Longev. 2016;2016:5818479.
  • Modi KP, Vishwakarma SL, Goyal RK, Bhatt PA. Beneficial effects of coenzyme Q10 in streptozotocin-induced type I diabetic rats. Iranian Journal Of Pharmacology & Therapeutics. 2006;5:61-5.
  • Elbe H, Öztürk F, Taşlıdere E, Çetin A, Doğan Z, Avcı S, et al. Wistar albino sıçanlarda streptozotocin ile oluşan diyabetik pankreas hasarında caffeic acid phenethyl ester (CAPE)’in tedavi edici etkileri. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi. 2015;2(1):22-9.
  • Sandikci M, Karagenc L, Yildiz M. Changes in the pancreas in experimental diabetes and the effect of lycopene on these changes: Proliferating, apoptotic, and estrogen receptor α positive cells. Anat Rec. 2017;300(11):2000-07.
  • García-Arévalo M, Alonso-Magdalena P, Servitja JM, Boronat-Belda T, Merino B, Villar-Pazos S, et al. Maternal exposure to bisphenol-A during pregnancy increases pancreatic β cell growth during early life in male mice offspring. Endocrinology. 2016;157(11):4158-71.
  • Poormoosavi SM, Najafzadehvarzi H, Behmanesh MA, Amirgholami R. Protective effects of asparagus officinalis extract against bisphenol A-induced toxicity in wistar rats. Toxicol Rep. 2018;5:427-33.
  • Korkmaz A, Ahbab MA, Kolankaya D, Barlas N. Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food Chem Toxicol. 2010;48(10):2865-71.
  • Aydoğan M, Korkmaz A, Barlas N, Kolankaya D. The effect of vitamin C on bisphenol A, nonylphenol and octylphenol induced brain damages of male rats. Toxicology. 2008;249(1): 35-9.
  • Markey CM, Wadia PR, Rubin BS, Sonnenschein C, Soto AM. Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract. Biol Reprod. 2005;72(6):1344-51.
  • Ibrahim MA, Elbakry RH, Bayomy NA. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat. Int J Exp Pathol. 2016;97(1):27-36.
  • Takao T, Nanamiya W, Nazarloo HP, Matsumoto R, Asaba K, Hashimoto K. Exposure to the environmental estrogen bisphenol A differentially modulated estrogen receptor-alpha and -beta immunoreactivity and mRNA in male mouse testis. Life Sci. 2003;72(10):1159-69.
  • Ahmed RA, ElGhamrawy TA, Salama EE. Effect of prenatal exposure to bisphenol a on the vagina of albino rats: immunohistochemical and ultrastructural study. Folia Morphol. 2014;73(4):399-408.
  • Sun IO, Jin L, Jin J, Lim SW, Chung BH, Yang CW. The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus. Korean J Intern Med. 2019;34(2): 365-74.
  • Lopez-Moreno J, Quintana-Navarro GM, Delgado-Lista J, Garcia-Rios A, Alcala-Diaz JF, Gomez-Delgado F et al. Mediterranean diet supplemented with coenzyme Q10 modulates the postprandial metabolism of advanced glycation end products in elderly men and women. J Gerontol A Biol Sci Med Sci. 2018;73(3):340-6.
There are 40 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Mustafa Yıldız 0000-0003-4128-8947

Özay Güleş 0000-0001-6170-1706

Mustafa Sandıkçı 0000-0002-9126-1016

Şadiye Kum 0000-0001-6586-4596

Publication Date December 25, 2020
Submission Date February 13, 2020
Acceptance Date October 12, 2020
Published in Issue Year 2020

Cite

Vancouver Yıldız M, Güleş Ö, Sandıkçı M, Kum Ş. Sıçanlarda Bisfenol A’nın Neden Olduğu Pankreatik Değişimler Üzerine Koenzim Q10’un Etkileri. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(3):335-41.

Cited By

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty