The Effect of Alpha Lipoic Acid on Pathogenesis of Experimental Nephrolithiasis and Epithelial Mesenchymal Transition


Publiée : Oct 31, 2023
Mis à jour : 2023-10-31
Versions :
2023-10-31 (2)
T Kutlu
https://orcid.org/0000-0002-8771-1256
F Kazak
A Uyar
Résumé

In this study, the effects of calcium oxalate (CaOx) crystal formation on the kidneys and the effect of alpha-lipoic acid (ALA) on this process were investigated in rats. The study consists of 6 groups with 10 rats in each group. Ethylene glycol (EG) and ammonium chloride (AC) (0.75% EG + 0.75% AC) were added to the drinking water of different groups for 7 or 14 days to induce nephrolithiasis. The effects of the CaOx on the kidneys and ALA (100 mg/kg/day/orally) on this process were investigated via histopathological, immunohistochemical, and biochemical methods. In the histopathological examination, EG+AC application for both 7 and 14 days caused crystal accumulation in the tubule lumens, cystically dilated tubules, and hydropic degeneration in the tubular epithelium. However, inflammatory cell infiltration was observed merely in 14 days. In the immunohistochemical examination, when EG+AC administration  was applied for 14 days only, it caused expression of ED1, alpha smooth muscle actin (α-SMA), and vimentin in the tubulointerstitial areas. However, α-SMA and vimentin expression was not observed in tubular epithelial cells. Transforming growth factor beta-1 (TGF-β1) expression was also detected in the tubular epithelium and intertubular cells at 14 days. It was determined that ALA administration with EG+AC application reduced the crystal accumulation in the tubule lumens (p<0.001), the degeneration of the tubular epithelium (p<0.001), and the expression of TGF-β1. In addition, it was detected that ALA caused an increase in glutathione peroxidase (GPx) (p<0.001) and Catalase (CAT) (p>0.05) activities, which decreased with EG+AC application. 

Article Details
  • Rubrique
  • Research Articles
Téléchargements
Les données relatives au téléchargement ne sont pas encore disponibles.
Références
Aebi H (1984) Catalase in vitro assay methods. Methods Enzymol, 105: 121-126.
Bahadoran H, Naghii MR, Mofid M, Asadi MH, Ahmadi K, Sarveazad A. (2016) Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat. Endocr Regul 50(4), 194-206.
Beutler E. (1975) Red cell metabolism. In: A Manual of Biochemical Methods. New York: Grune Strottan, 67-69.
Boevé ER, Ketelaars GAM, Vermeij M, Cao LC, Schröder FH, De Bruijn WC. (1993) An ultrastructural study of experimentally induced microliths in rat proximal and distal tubules. J Urol, 149(4), 893-899.
Branton MH, Kopp JB. (1999) TGF-β and fibrosis. Microbes and infect, 1(15), 1349-1365.
Cao Q, Harris DC, Wang Y. (2015) Macrophages in kidney injury, inflammation, and fibrosis. Physiology, 30(3), 183-194.
Cavdar Z, Oktan MA, Ural C, Kocak A, Calisir M, Heybeli C, Cavdar C. (2021) Alpha lipoic acid attenuates iron induced oxidative acute kidney injury in rats. Biotech Histochem, 96(6), 409-417.
Convento MB, Pessoa EA, Cruz E, da Glória MA, Schor N, Borges FT. (2017) Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: contribution to oxalate kidney injury. Sci Rep, 7(1), 1-12.
de Water R, Noordermeer C, Houtsmuller AB, Nigg AL, Stijnen T, Schröder FH, Kok DJ. (2000) Role of macrophages in nephrolithiasis in rats: an analysis of the renal interstitium. Am J Kidney Dis, 36(3), 615-625.
Ergene E. (2018) Alfa lipoik asit ve metabolik etkileri üzerine bir araştirma. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 2(3), 159-165.
Fan J, Glass MA, Chandhoke PS. (1999) Impact of ammonium chloride administration on a rat ethylene glycol urolithiasis model. Scanning Microsc, 13(2-3), 299-306.
Gröne HJ, Weber K, Gröne E, Helmchen U, Osborn M. (1987) Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney. Am J Clin Pathol, 129(1), 1.
Gunes A, Ozmen O, Saygın M, Ascı H, Tok L, Tok O, Dıncoglu D. (2016) Lens and cornea lesions of rats fed corn syrup and the protective effects of alpha lipoic acid. Cutan Oocul Toxicol, 35(1), 31-35.
Hu H, Chen W, Ding J, Jia M, Yin J, Guo Z. (2015) Fasudil prevents calcium oxalate crystal deposit and renal fibrogenesis in glyoxylate-induced nephrolithic mice. Exp Molecular Pathol, 98(2), 277-285.
Jercan O, Penescu M, Malaescu DG. (2012) Immunoexpression of alpha-SMA and CD68 in native kidney biopsies. Rom J Morphol Embryol, 53(4), 1037-1042.
Kang KP, Kim DH, Jung YJ, Lee AS, Lee S, Lee SY, Kim W. (2009) Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation. Nephrol Dial Transplant, 24(10), 3012-3020.
Kanlaya R, Sintiprungrat K, Thongboonkerd V. (2013) Secreted products of macrophages exposed to calcium oxalate crystals induce epithelial mesenchymal transition of renal tubular cells via RhoA-dependent TGF-β1 pathway. Cell biochem and biophys, 67(3), 1207-1215.
Kazak F, Çimrin T, Alaşahan S. (2020) Effects of Ground Fennel Seed Supplementation to diet on Some Blood and Liver Parameters in Quails. ISPEC Journal of Agr. Sciences. 4(4):1037-1052.
Khan SR. (1991) Pathogenesis of oxalate urolithiasis: lessons from experimental studies with rats. Am J Kidney Dis., 17(4), 398-401.
Khan SR. (1997) Animal models of kidney stone formation: an analysis. World J Urol, 15(4), 236-243.
Khan SR. (2004) Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies. Clin Exp Nephrol, 8(2), 75-88.
Kowluru RA, Odenbach S. (2004) Effect of long-term administration of α-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes, 53(12), 3233-3238.
Kutlu T, Alcigir G. (2019) Comparison of renal lesions in cats and dogs using pathomorphological and ımmunohistochemical methods. Biotech Histochem, 94(2), 126-133.
Lee YH, Huang WC, Chiang H, Chen MT, Huang JK. (1992) Determinant role of testosterone in the pathogenesis of urolithiasis in rats. J Urol, 147(4), 1134-1138.
Liu M, Liu YZ, Feng Y, Xu YF, Che JP, Wang GC, Zheng JH. (2013) Novel evidence demonstrates that epithelial-mesenchymal transition contributes to nephrolithiasis-induced renal fibrosis. J Surg Res, 182(1), 146-152.
Luna, LG, (ed), Manual of Staining Methods of the AFIP, 3 rd edition, McGraw-Hill, NY, c 1968, p 177.
Manissorn J, Khamchun S, Vinaiphat A, Thongboonkerd V. (2016) Alpha-tubulin enhanced renal tubular cell proliferation and tissue repair but reduced cell death and cell-crystal adhesion. Sci Rep, 6(1), 1-12.
Nakatsuji S, Yamate J, Sakuma S. (1998) Relationship between vimentin expressing renal tubules and interstitial fibrosis in chronic progressive nephropathy in aged rats. Virchows Arch, 433(4), 359-367.
Ng YY, Huang TP, Yang WC, Chen ZP, Yang AH, Mu W, Lan HY. (1998) Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int, 54(3), 864-876.
O’Kell AL, Grant DC, Khan SR. (2017) Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis, 45(4), 329-336.
Panigrahi PN, Dey S, Sahoo M, Dan A (2017) Antiurolithiatic and antioxidant efficacy of Musa paradisiaca pseudostem on ethylene glycol-induced nephrolithiasis in rat. Indian J Pharmacol. 49(1): 77–83.
Pizzolato PJ. (1964) Histochem. Cytochem., 12:333-336
Rule AD, Bergstralh EJ, Melton LJ, Li X, Weaver AL, Lieske JC (2009) Kidney stones and the risk for chronic kidney disease. Clin J Am Soc Nephrol, 4(4), 804-811.
Shirfule AL, Racharla V, Qadri SSYH, Khandare AL. (2013) Exploring antiurolithic effects of gokshuradi polyherbal ayurvedic formulation in ethylene-glycol-ınduced urolithic rats. Evid Based Complement Alternat Med. 763720.
Thamilselvan S, Khan SR, Menon M. (2003) Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res, 31(1), 3-9.
Topsakal S, Ozmen O, Ozgocmen M (2019) Effects of alpha-lipoic acid on high fructose induced hepatic pathology. Biotech Histochem, 94(4), 271-276.
Wang Z, Bai Y, Wang J, Wang J. (2020) The preventive and therapeutic effects of α-lipoic acid on ethylene glycol-induced calcium oxalate deposition in rats. Int Urol Nephrol, 52(7), 1227-1234.
Wiessner JH, Hasegawa AT, Hung LY, Mandel GS, Mandel NS. (2001) Mechanisms of calcium oxalate crystal attachment to injured renal collecting duct cells. Kidney Int, 59(2), 637-644.
Yamate J, Kuribayashi M, Kuwamura M, Kotani T, Ogihara K. (2005) Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys, and in kidney-related cell lines under fibrogenic stimuli. Exp Toxicol Pathol, 57(2), 135-147.
Yu X, Liu H, Zou J, Zhu J, Xu X, Ding X. (2012) Oxidative stress in 5/6 nephrectomized rat model: effect of alpha-lipoic acid. Ren Fail, 34(7), 907-914.
Articles les plus lus par le même auteur ou la même autrice