Ratlarda Bisphenol A ile İndüklenen Nefrotoksisitede Kidney İnjury Molecule -1 Üzerine p-Kumarik Asitin Etkileri

BisfenolA(BPA); polikarbonat plastiklerin, epoksi reçinelerin ve diğer birçok polimer malzemelerin sentezinde yaygın olarak kullanılan endüstriyel bir kimyasaldır. Seri üretimleri ve yaygın kullanım alanları nedeniyle çevrede bol miktarda bulunmaktadır. BPA, birçok doku ve organda hasara yol açmaktadır. Bu çalışmada BPA ile indüklenen nefrotoksisitede kidney injury molecule-1(KİM-1) seviyesi üzerine p-kumarik asit(PCA)’in etkileri araştırıldı. Çalışmada erkek erişkin 40 adet rat kullanıldı. Her grupta 8 ratın bulunduğu 5 deney grubu oluşturuldu. Kontrol grubuna 14 gün boyunca intragastrik(i.g.) 1ml serum fizyolojik verildi. BPA(100) grubuna 14 gün boyunca 100 mg/kg dozunda i.g. BPA verildi. PCA(50)+BPA(100) ve PCA(100)+BPA(100) gruplarına 14 gün boyunca 100mg/kg BPA ile birlikte sırasıyla 50 ve 100 mg/kg dozunda i.g. PCA verildi. PCA(100) grubuna ise 14 gün boyunca 100 mg/kg dozunda PCA verildi. Deneyin 15. günü, ratlar anestezi altına alındı ve sonrasında böbrek dokuları toplandı. Böbrek dokularında KİM-1 düzeyleri analiz edildi. Sonuçlar gruplar arasında değerlendirildi. BPA(100) grubunda KİM-1 düzeylerinin kontrole göre önemli düzeyde arttığı belirlendi. PCA’nın düşük dozunun KİM-1 düzeyindeki artışı anlamlı düzeyde önleyemedi. PCA(100)+BPA(100) ve PCA(100) gruplarında KİM-1 seviyelerinin kontrol grubuna benzediği belirlendi. Bu çalışmanın sonucunda, ratlarda BPA ile indüklenen nefrotoksisitede PCA’nın özellikle yüksek dozunun koruyucu etkili olduğu ve KİM-1 düzeylerindeki artışı önemli düzeyde önlediği belirlendi.

Effects of p-Coumaric Acid on Kidney Injury Molecule-1 in Bisphenol A-induced Nephrotoxicity in Rats

Bisphenol A(BPA); It is an industrial chemical widely used in the synthesis of polycarbonate plastics, epoxy resins and many other polymer materials. It is abundant in the environment due to its mass production and widespread use. BPA causes damage to many tissues and organs. In this study, the effects of p-coumaric acid(PCA) on kidney injury molecule-1(KIM-1) level in BPA-induced nephrotoxicity were investigated. Forty male adult rats were used in the study. 5 experimental groups with 8 rats in each group were formed. The control group was given 1 ml of saline intragastric (i.g.) for 14 days. BPA(100) group was given 100 mg/kg i.g. PCA(50)+BPA(100) and PCA(100)+BPA(100) groups were given 100mg/kg BPA together with i.g PCA at a dose of 50 and 100mg/kg, respectively, for 14 days. PCA(100) group was given PCA at a dose of 100 mg/kg for 14 days. On the 15th day of the experiment, the rats were anesthetized and then kidney tissues were collected. KIM-1 levels in kidney tissues were analyzed. Results were evaluated among groups. It was determined that, KIM-1 levels were significantly increased in the BPA(100) group compared to the control group. The low dose of PCA could not significantly prevent the increase in KIM-1 level. It was determined that KIM-1 levels in PCA(100)+BPA(100) and PCA(100) groups were similar to the controlgroup. As a result of this study, it was determined that, especially high dose of PCA, had a protective effect in BPA-induced nephrotoxicity in rats and significantly prevented the increase in KIM-1 levels.

___

  • Akdemir FNE., Albayrak M., Çalik M., Bayir Y., Gülçin İ., 2017. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines, 5(2), 18.
  • Al FM., Otifi H., Alshyarba M., Dera AA., Rajagopalan P., 2020. Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KİM-1 and ameliorating Nrf2/HO-1 signalling. J Drug Target, 28(9), 913-922.
  • Al-Kuraishy HM., Al-Gareeb AI., Rasheed HA., 2019. Antioxidant and anti-inflammatory effects of curcumincontribute into attenuation of acute gentamicin-induced nephrotoxicity in rats. Asian J Pharm Clin Res, 12(3), 466-468.
  • Amin RP., Vickers AE., Sistare F., Thompson KL., Roman RJ., Lawton M., Afshari CA., 2004. Identification of putative gene based markersof renal toxicity. Environ Health Perspect, 112, 465–79.
  • Aslanturk A., Uzunhisarcikli M., 2020. Protective potential of curcumin or taurine on nephrotoxicity caused by bisphenol A. ESPR, 27(19), 23994-24003.
  • Bailly V., Zhang Z., Meier W., Cate R., Sanicola M., Bonventre JV., 2002. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem, 277(42), 39739-39748.
  • Bailly V., Zhang Z., Meier W., Cate R., Sanicola M., Bonventre JV., 2002. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem, 277, 39739–48.
  • Behmanesh MA., Najafzadehvarzi H., Poormoosavi SM., 2018. Protective Effect of Aloe vera Extract against Bisphenol A Induced Testicular Toxicity in Wistar Rats. Cell J, 20(2), 278.
  • Bonventre JV., 2009. Kidney injury molecule-1 (KİM-1): a urinary biomarker and much more. Nephrol Dial Transplant, 24, 3265–8.
  • Boz H., 2015. p‐Coumaric acid in cereals: presence, antioxidant and antimicrobial effects. Int J Food Sci, 50.11, 2323-2328.
  • Elobeid MA., Zeinab KH., 2015. Bisphenol-A induced oxidative stress and apoptosis in kidney of male rats. J Environ Biol, 36.3, 685.
  • Gelen V., Şengül E., Yıldırım S., Atila G., 2018. The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci, 21, 404-410.
  • Gelen V., Şengül E., Yıldırım S., Senturk E., Tekin S., Kükürt A., 2021. The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environ Sci Pollut Res, 1-10.
  • Güleş Ö., Kum Ş., Yıldız M., Boyacıoğlu M., Ahmad E., Naseer Z., Eren Ü., 2019. Protective effect of coenzyme Q10 against bisphenol-A-induced toxicity in the rat testes. Toxicol. Ind. Health, 35(7), 466-481.
  • Haroun MR., Zamzam IS., Metwally ES., EL-Shafey RS., 2019. Effect of vitamin c on bisphenol a induced hepato& nephrotoxicity in albino rats. EJFSAT, 16(Supplement), 57-85.
  • Hines CJ., Jackson MV., Deddens JA., Clark JC., YeX., Christianson AL., Meadows JW., Calafat AM., 2017. Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA inthe USA. Ann Work Expo Health, 61, 164–182.
  • Ichimura T., Asseldonk EJ., Humphreys BD., Gunaratnam L., Duffield JS., Bonventre JV.,2008. Kidney injury molecule–1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest, 118(5), 1657-1668.
  • Ichimura T., Bonventre JV., Bailly V., Wei H., Hession CA., Cate RL., Sanicola M., 1998. Kidney injury molecule-1 (KİM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem, 273, 4135–42.
  • Ichimura T., Brooks CR., Bonventre JV., 2012. KİM-1/Tim-1 and immune cells: shifting sands. Kidney Int, 81, 809–11.
  • Ichimura T., Hung CC., Yang SA., Stevens JL., Bonventre JV., 2004. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol, 286, F552–63.
  • IshtiaqA., Ali T., Bakhtiar A., Bibi R., Bib K., Mushtaq I., Murtaza I., 2021. Melatonin abated Bisphenol A–induced neurotoxicity via p53/PUMA/Drp-1 signaling. ESPR, 28(14), 17789-17801.
  • Kataria A., Trasande L., Trachtman H., 2015. The effects of environmental chemicals on renal function. Nat Rev Nephrol, 11, 610–625.
  • Khan S., Beigh S., Chaudhari BP., Sharma S., Aliul Hasan Abdi S., Ahmad S., Ahmad F., Parvez S., Raisuddin S., 2016. Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats. Environ. Toxicol, 31, 1922–1934.
  • Kiliç I., Yeşiloğlu Y., 2013. Spectroscopic studies on the antioxidant activity of p-coumaric acid. Spectrochim Acta A Mol Biomol Spectrosc, 115, 719-724.
  • Kobroob A., Peerapanyasut W., Chattipakorn N., WongmekiatO., 2018. 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, 3082438.
  • Medic B., Rovcanin B., Vujovic KS., Obradovic D., Duric D., Prostran M., 2016. Evaluation of novel biomarkers of acute kidney injury: the possibilities and limitations. Curr Med Chem, 23, 1981–97.
  • Oyeleye SI., Adefegha SA., Dada FA., Okeke BM., Oboh G., 2019. Effect of p‐coumaric acid on the erectogenic enzyme activities and non‐protein thiol level in the penile tissue of normal and doxorubicin‐induced oxidative stress male rat. Andrologia, 51(6), e13281.
  • Pennemans V., Rigo JM., Faes C., Reynders C., Penders J., Swennen Q., 2013. Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue?. Clin Chem Lab Med, 51, 1795–802.
  • Prozialeck WC., Vaidya VS., Liu J., Waalkes MP., Edwards JR., Lamar PC., Bonventre JV., 2007. Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. Kidney Int, 72, 985–93.
  • Rafiee Z., Moaiedi MZ., Gorji AV., Mansouri E., 2020. p-Coumaric acid mitigates doxorubicin-induced nephrotoxicity through suppression of oxidative stress, inflammation and apoptosis. Arch. Med. Res, 51(1), 32-40.
  • Rezg R., El-Fazaa S., Gharbi N., Mornagui B., 2014. Bisphenol A and human chronic diseases: Current evidences,possible mechanisms, and future perspectives. Environ Int, 64, 83–90.
  • Sabitha R., Nishi K., Gunasekaran VP., Annamalai G., AgilanB., Ganeshan M., 2019. p-Coumaric acid ameliorates ethanol–induced kidney injury by inhibiting inflammatory cytokine production and NF–κB signaling in rats. Asian Pac J Trop Biomed, 9(5), 188.
  • Sahindokuyucu KF., Erdemli KSB., Erol Z., Garlı S., 2021. The protective effect of p-coumaric acid on toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats. RECIA, 13(1), e843-e843.
  • Sengul E., Gelen V., Yıldırım S., Çelebi F., Çınar A., 2019. Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats. Asian Pac J Trop Biomed, 9(3), 116-122.
  • Sengul E., Gelen V., Yildirim S., Tekin S., Dag Y., 2021. The Effects of Selenium in Acrylamide-Induced Nephrotoxicity in Rats: Rolesof Oxidative Stress, Inflammation, Apoptosis, and DNA Damage. Biol Trace Elem Res, 199(1), 173-181.
  • Shirani M., Alizadeh S., Mahdavinia M., Dehghani MA., 2019. The ameliorative effect of quercetin on bisphenol A-induced toxicity in mitochondria isolated from rats. ESPR, 26(8), 7688-7696.
  • Trasande L., Attina TM., Trachtman H., 2013. Bisphenol A exposure is associated with low-grade urinary albuminexcretion in children of the United States. Kidney Int, 83, 741–748.
  • Valokola MG., Karimi G., Razavi BM., Kianfar M., Jafarian AH., Jaafari MR., Imenshahidi M., 2019. The protective activity of nanomicelle curcumin in bisphenol A‐induced cardiotoxicity followingsubacute exposure in rats. Environ, 34(3), 319-329.
  • Wahby MM., Abdallah ZM., Abdou HM., Yousef MI., Newairy ASA., 2017. Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats. EJBAS, 4(4), 350-357