Sıçanlarda Poliklorlu Bifenil (Aroklor 1254) ile Oluşturulan Nefrotoksisite Üzerine Alfa Lipoik Asitin Etkisi

Yıl 2023, , 504 - 512, 31.12.2023

Mustafa Yıldız

https://doi.org/10.30607/kvj.1364111

Öz

Sunulan çalışma, PCB (Aroklor 1254)’ye maruz bırakılan sıçanların böbreklerindeki morfolojik değişikliklerin belirlenmesini ve bu değişiklikler üzerine ALA'nın etkilerinin ortaya çıkarılmasını amaçladı. Sıçanlar kontrol, ALA, PCB ve ALA+PCB olmak üzere rastgele dört gruba ayrıldı. ALA ve PCB uygulamaları otuz gün boyunca devam etti. Deney sonunda hayvanlardan doku örnekleri alındı. Histopatolojik ve histomorfometrik incelemeler için böbrek kesitlerine Crossmon’un üçlü boyama yöntemi uygulandı. Ayrıca doku kesitlerinde periyodik asit-Schiff (PAS) reaksiyonu incelendi. Histopatolojik açıdan, böbrekte glomerüler dejenerasyon ile bağ doku yoğunluklarının kontrol grubuna göre PCB grubunda anlamlı bir şekilde arttığı tespit edildi. Bununla birlikte, glomerüler dejenerasyon yoğunluğunun PCB grubuna göre ALA+PCB grubunda anlamlı bir şekilde azaldığı saptandı. Böbrekte renal korpüskül, proksimal tübül, çıkan henle ve toplayıcı kanal çaplarının kontrol grubuna göre PCB grubunda anlamlı bir şekilde azaldığı belirlendi. Ancak bu parametreler PCB grubuna göre ALA+PCB grubunda anlamlı bir şekilde arttı. Böbrekte glomerüler mezengial matriks yoğunluğu ile proksimal tübül epitelindeki glikojen yoğunluğu kontrol grubuna göre PCB grubunda anlamlı bir şekilde artarken, bu parametreler PCB grubuna göre ALA+PCB grubunda anlamlı bir şekilde azaldı. Sonuç olarak, PCB böbrek histolojisinde bozukluklara neden olarak renal fonksiyonları olumsuz etkileyebilir. Bununla birlikte, PCB maruziyetine karşı ALA kullanımı böbrek dokusunun korunmasına katkı sağlayabilir.

Anahtar Kelimeler

Alfa lipoik asit, Aroklor 1254, Böbrek, Histoloji, Sıçan

Effect of Alpha Lipoic Acid on Polychlorinated Biphenyl (Aroclor 1254)-Induced Nephrotoxicity in Rats

Öz

The present study aimed to determine the morphological changes in rat kidneys exposed to PCB (Aroclor 1254) and to reveal the effects of ALA on those changes. Rats were randomly divided into four groups: Control, ALA, PCB and ALA+PCB. The applications of ALA and PCB continued for thirty days. At the end of the experiment, the tissue samples were taken from the animals. Crossmon’s triple staining method was applied to kidney sections for histopathological and histomorphometric examinations. In addition, the periodic acid-Schiff (PAS) reaction was examined in tissue sections. Histopathologically, it was determined that glomerular degeneration and connective tissue densities in the kidney significantly increased in PCB group compared to Control group. Besides, it was found that glomerular degeneration intensity significantly decreased in ALA+PCB group compared to PCB group. It was detected that the diameters of the renal corpuscle, proximal tubule, ascending limb of Henle’s loop and collecting duct in the kidney significantly decreased in PCB group compared to Control group. However, these parameters significantly increased in ALA+PCB group compared to PCB group. While the density of glomerular mesangial matrix and glycogen density in proximal tubule epithelium significantly increased in PCB group compared to Control group, these parameters significantly decreased in ALA+PCB group compared to PCB group. As a result, PCB may adversely affect renal functions by causing disorders in kidney histology. In addition, the use of ALA against PCB exposure may contribute to the preservation of kidney tissue.

Anahtar Kelimeler

Alpha lipoic acid, Aroclor 1254, Histology, Kidney, Rat

Etik Beyan

This study was carried out at Aydin Adnan Menderes University Experiment Animals Application Center. The study was approved by Aydin Adnan Menderes University Animal Experiments Local Ethics Committee (ADUHADYEK Ref No: 6458310/2021/180).

Teşekkür

I would like to thank Prof. Dr. Ulker Eren and Associate Prof. Ozay Gules for their guidance and support.

Kaynakça

• Aydin, M., Canpolat, S., Seyran, A. D., Bulmus, O. & Yilmaz, B. (2007). Poliklorlu bifenillerin sıçan korteks, hipokampus, striatum ve hipotalamus dokusunda katekolaminerjik nörotransmiter düzeylerine etkileri. Fırat Tıp Dergisi, 12(2), 88-92. https://dergipark.org.tr/tr/pub/firattip/issue/6366/85009
• Bae, E. H., Lee, J., Ma, S. K., Kim, I. J., Frøkiaer, J., Nielsen, S., Kim, S. Y., & Kim, S. W. (2009). Alpha-lipoic acid prevents cisplatin-induced acute kidney injury in rats. Nephrology, Dialysis, Transplantation, 24(9), 2692-2700. https://doi.org/10.1093/ndt/gfp176
• Banudevi, S., Krishnamoorthy, G., Venkataraman, P., Vignesh, C., Aruldhas, M. M., & Arunakaran, J. (2006). Role of alpha-tocopherol on antioxidant status in liver, lung, and kidney of PCB exposed male albino rats. Food and Chemical Toxicology, 44(12), 2040-2046. https://doi.org/10.1016/j.fct.2006.07.017
• Bhatti, F., Mankhey, R. W., Asico, L., Quinn, M. T., Welch, W. J., & Maric, C. (2005). Mechanisms of antioxidant and pro-oxidant effects of alpha-lipoic acid in the diabetic and nondiabetic kidney. Kidney International, 67(4), 1371-1380. https://doi.org/10.1111/j.1523-1755.2005.00214.x
• Bruner-Tran, K. L., & Osteen, K. G. (2010). Dioxin-like PCBs and endometriosis. Systems Biology in Reproductive Medicine, 56(2), 132-146. https://doi.org/10.3109/19396360903381023
• Cakir, T., Polat, C., Basturk, A., Gul, M., Aslaner, A., Durgut, H., Sehirli, A. O., Aykac, A., Bahar, L., & Sabuncuoglu, M. Z. (2015). The effect of alpha-lipoic acid on rat kidneys in methotrexate-induced oxidative injury. European Review for Medical and Pharmacological Sciences, 19(11), 2132-2139.
• Carpenter, D. O. (2005). Environmental contaminants and human health: The health effects of persistent toxic substances. Fırat Tıp Dergisi, 10(1), 1-4.
• El-Sawalhi, M. M., & Raafat, M. (2007). Effect of alpha-lipoic acid on oxidative stress status in rat kidney subjected to ischemia/reperfusion injury. The Egyptian Journal of Biochemistry and Molecular Biology, 25(1), 59-76. https://doi.org/ 10.4314/ejbmb.v25i1.35946
• Ghosh, S., De, S., Chen, Y., Sutton, D. C., Ayorinde, F. O., & Dutta, S. K. (2010). Polychlorinated biphenyls (PCB-153) and (PCB-77) absorption in human liver (HepG2) and kidney (HK2) cells in vitro: PCB levels and cell death. Environmental International, 36(8), 893-900. https://doi.org/ 10.1016/j.envint.2010.06.010
• Grdović, N., Rajić, J., Arambašić Jovanović, J., Dinić, S., Tolić, A., Đorđević, M., Đorđević, M., Trifunović, S., Vidaković, M., Uskoković, A., & Mihailović, M. (2021). α-Lipoic acid increases collagen synthesis and deposition in nondiabetic and diabetic rat kidneys. Oxidative Medicine and Cellular Longevity, 2021, 6669352. https://doi.org/10.1155/2021/6669352
• Guimaraes, S. B., Santos, J. M. V., Aragao, A. A., Kimura, O. D. S., Barbosa, P. H. U., & Vasconcelos, P. R. L. (2007). Protective effect of α-lipoic acid in experimental spermatic cord torsion. Nutrition, 23(1), 76-80. https://doi.org/10.1016/j.nut.2006.09.005
• Gules, O., Dogan, G., Ercins, U. H., & Eren, U. (2022). Effects of quercetin against doxorubicin-induced testicular toxicity in male rats. Biological Bulletin of the Russian Academy of Sciences, 49, 203-213. https://doi.org/10.1134/S1062359022030086
• Gules, O., & Eren, U. (2016). Protective role of alpha lipoic acid against polychlorobiphenyl (Aroclor 1254)-induced testicular toxicity in rats. Romanian Journal of Morphology and Embryology, 57(2), 451-459.
• Gultekin, B., Tuncer, S., & Burat, I. (2021). Protective effects of alpha lipoic acid on ischemia-reperfusion induced kidney damage. Journal of Medical Sciences and Health, 7(3), 51-58. https://doi.org/10.46347/jmsh.2021.v07i03.011
• Hsu, P. C., Pan, M. H., Li, L. A., Chen, C. J., Tsai, S. S., & Guo, Y. L. (2007). Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis related gene expression in rat offspring. Toxicology and Applied Pharmacology, 221(1), 68-75. https://doi.org/10.1016/j.taap.2007.01.027
• Jamor, P., Ahmadvand, H., Ashoory, H., & Babaeenezhad, E. (2019). Effect of alpha-lipoic acid on antioxidant gene expression and kidney injury in alloxan-induced diabetic rats. Journal of Nephropathology, 8(1), e06. https://doi.org/10.15171/jnp.2019.06
• Karaca, E. G., & Sozbilir, N. B. (2007). Dietilnitrozamin verilen ratlarda alfa lipoik asidin koruyucu etkilerinin araştırılması. Medical Journal of Kocatepe, 7, 11-17. https://doi.org/10.18229/ktd.47416
• Kutlu, S., Colakoglu, N., Halifeoglu, I., Sandal, S., Seyran, A. D., Aydin, M., & Yilmaz, B. (2007). Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats. Cell Biochemistry and Function, 25(2), 167-172. https://doi.org/10.1002/cbf.1289
• Lilienthal, H., Fastabend, A., & Hany, J. (2000). Reduced levels of 1,25-Dihydroxyvitamin D3 in rat dams and offspring after exposure to a reconstituted PCB mixture. Toxicological Sciences, 57(2), 292-301. https://doi.org/10.1093/toxsci/57.2.292
• Lindell, B. (2012). Polychlorinated biphenyls (PCBs). Environmental Medicine at Sahlgrenska Academy, 46(1).
• Lu, C. F., Wang, Y. M., Peng, S. Q., Zou, L. B., Tan, D. H., Liu, G., Fu, Z., Wang, Q. X., & Zhao, J. (2009). Combined effects of repeated administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls on kidneys of male rats. Archives of Environmental Contamination and Toxicology, 57(4), 767-776. https://doi.org/10.1007/s00244-009-9323-x
• Mervaala, E., Finckenberg, P., Lapatto, R., Müller, D. N., Park, J. K., Dechend, R., Ganten, D., Vapaatalo, H., & Luft, F. C. (2003). Lipoic acid supplementation prevents angiotensin II-induced renal injury. Kidney International, 64(2), 501-508. https://doi.org/10.1046/j.1523-1755.2003.00108.x
• Morakinyo, A. O., Oludare, G. O., Anifowose, A. A., & Adegoke, O. A. (2012). Protective effects of alpha lipoic acid on carbon tetrachloride-induced liver and kidney damage in rats. British Journal of Pharmacology and Toxicology, 3(1), 21-28.
• Murugesan, P., Balaganesh, M., Balasubramanian, K., & Arukaran, J. (2007). Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells. Journal of Endocrinology, 192(2), 325-338. https://doi.org/10.1677/joe.1.06874
• Oksala, N. K., Lappalainen, J., Laaksonen, D. E., Khanna, S., Kaarniranta, K., Sen, C. K., & Atalay, M. (2007). Alpha-lipoic Acid modulates heat shock factor-1 expression in streptozotocin-induced diabetic rat kidney. Antioxidants & Redox Signaling, 9(4), 497-506. https://doi.org/10.1089/ars.2006.1450
• Oktan, M. A., Heybeli, C., Ural, C., Kocak, A., Bilici, G., Cavdar, Z., Ozbal, S., Arslan, S., Yilmaz, O., & Cavdar, C. (2021). Alpha-lipoic acid alleviates colistin nephrotoxicity in rats. Human & Experimental Toxicology, 40(5), 761-771. https://doi.org/10.1177/0960327120966043
• Oskam, I. C., Ropstad, E., Smith, A. J., Skaare, J. U., Tverdal, A., Berg, K. A., & Viger, R. (2004). Effects of PCB 99 and PCB 153 exposure on spermatogenesis in young adult C57BL6 mice. Reproductive Toxicology, 19(2), 169-180. https://doi.org/ 10.1016/j.reprotox.2004.07.005
• Padmalayam, I., Hasham, S., Saxena, U., & Pillarisetti, S. (2009). Lipoic acid synthase (LASY) a novel role in inflammation, mitochondrial function, and insulin resistance. Diabetes Journals, 58(3), 600-608. https://doi.org/10.2337/db08-0473
• Pradhan, S., Mandal, S., Roy, S., Mandal, A., Das, K., & Nandi, D. K. (2013). Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen induced uremic rats. Saudi Pharmaceutical Journal, 21(2), 187-192. https://doi.org/ 10.1016/j.jsps.2012.03.003
• Raja, J., Pathak, S., & Kundu, R. (2019). Low dose and subchronic Aroclor 1254 induced histopathological changes in mice kidney. Journal of Applied Biology and Biotechnology, 7(03), 59-62. https://doi.org/10.7324/JABB.2019.70311
• Seyran, A., & Erisir, M. (2008). Poliklorlu bifeniller ve sağlık üzerine etkileri. Fırat Üniversitesi Sağlık Bilimleri Veteriner Dergisi, 22(1), 33-40.
• Singh, U., & Jialal, I. (2008). Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews, 66(11), 646-657. https://doi.org/10.1111/j.1753-4887.2008.00118.x
• Sirca, T., Onder, A., Kapan, M., Tekin, R., Firat, U., Evliyaoglu, O., & Taskesen, F. (2012). Ratlarda oluşturulan deneysel ince bağırsak obstrüksiyonlarında splenektominin bakteriyel translokasyon ve inflamatuvar değişikliklere etkisi. Turkish Journal of Surgery, 28, 001-007. https://doi.org/10.5097/1300-0705.UCD.1400-12.05
• Sonne, C., Wolkers, H., Leifsson, P. S., Jenssen, B. M., Fuglei, E., Ahlstrøm, O., Dietz, R., Kirkegaard, M., Muir, D. C., & Jørgensen, E. (2008). Organochlorine-induced histopathology in kidney and liver tissue from Arctic fox (Vulpes lagopus). Chemosphere, 71(7), 1214-1224.
• Sula, E., Aliko, V., Marku, E., Nuro, A., & Faggio, C. (2020). Evaluation of kidney histopathological alterations in Crucian Carp, Carassius carassius, from a pesticide and PCB-contaminated freshwater ecosystem, using light microscopy and organ index mathematical model. International Journal of Aquatic Biology, 8(3), 154-165.
• Tomooka, S., Border, W. A., Marshall, B. C., & Noble, N. A. (1992). Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. Kidney International, 42, 1462-1469. https://doi.org/10.1038/ki.1992.442
• Valko, M., Rhodes, C. J., Moncola, J., Izakovic, M., & Mazura, M. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions, 160(1), 1-40. https://doi.org/10.1016/j.cbi.2005.12.009
• Winiarska, K., Malinska, D., Szymanski, K., Dudziak, M., & Bryla, J. (2008). Lipoic acid ameliorates oxidative stress and renal injury in alloxan diabetic rabbits. Biochimie, 90(3), 450-459. https://doi.org/10.1016/j.biochi.2007.11.010
• Wongmekiat, O., Leelarungrayub, D., & Thamprasert, K. (2013). Alpha-lipoic acid attenuates renal injury in rats with obstructive nephropathy. BioMed Research International, 2013, 138719. https://doi.org/10.1155/2013/138719