Evaluating Adropine levels in kidney tissue after Methotrexate treatment in rats: a prospective experimental study

  • Karakeci Ahmet Firat University, School of Medicine, Department of Urology. Elazig, Türkiye
  • Kuloglu Tuncay Firat University, School of Medicine, Department of Histology and Embryology. Elazig, Türkiye
  • Acisu Tutku Can Firat University, Faculty of Veterinary Medicine, Department of Reproduction and Artificial Insemination. Elazig, Türkiye
  • Keles Ahmet Istanbul Medeniyet University, School of Medicine, Department of Urology. Istanbul, Türkiye
  • Ozan Tunc Firat University, School of Medicine, Department of Urology. Elazig, Türkiye
  • Vural Osman Firat University, School of Medicine, Department of Histology and Embryology. Elazig, Türkiye
  • Orhan Irfan Firat University, School of Medicine, Department of Urology. Elazig, Türkiye
  • Sabaz Karakeci Emel Health Sciences University, Elazig Fethi Sekin City Hospital, Department of Physical Therapy and Rehabilitation. Elazig, Türkiye
Keywords: Antioxidants, adropin protein, kidney diseases, Methotrexate, oxidative stress

Abstract

In this study, it was aimed to investigate Adropin levels in kidney tissues after Methotrexate (MTX) administration to identify potential changes following administration of agents with antioxidant/anti–inflammatory potential. Twenty four adult rats male albino Wistar rats were used in this study, and randomly divided into four groups. Control: These rats did not receive any treatment during the 14–day (d) experiment. N–acetylcysteine (NAC): These rats were administered 100 mg·kg-1·day-1 NAC intraperitoneally (i.p.) for 14 d. MTX: A single dose of 20 mg·kg-1 MTX was administered i.p. at the beginning of the study. MTX+ NAC: A single dose of 20 mg·kg-1 MTX was administered i.p. at the beginning of the study, and the rats were given 100 mg·kg-1·day-1 NAC i.p. for 14 d. Total antioxidant, and serum Adropin levels were found to be the lowest in the MTX group while the oxidant levels were significantly lower in the MTX group than in the MTX+NAC group (P<0.001). TUNEL positivity was similar among the groups, and no significant differences were observed. It was considered that these findings have shed light on the role of Adropin in the development of kidney failure following MTX administration.

Downloads

Download data is not yet available.

References

Onopiuk A, Tokarzewicz A, Gorodkiewicz E. Cystatin C: a kidney function biomarker. Adv. Clin. Chem. [Internet]. 2015; 68:57–69. doi: https://doi.org/9hc

Paueksakon P, Fogo AB. Drug–induced nephropathies. Histopathol. [Internet]. 2017; 70(1):94–108. doi: https://doi.org/mb9h

Abd El–Twab SM, Hozayen WG, Hussein OE, Mahmoud AM. 18β–Glycyrrhetinic acid protects against methotrexate–induced kidney injury by up–regulating the Nrf2/ARE/HO–1 pathway and endogenous antioxidants. Ren. Fail. [Internet]. 2016; 38(9):1516–1527. doi: https://doi.org/gr8n6z

Kozub P, Simaljakova M. Systemic therapy of psoriasis: methotrexate. Bratisl Lek Listy. [Internet]. 2011; 112(7):390–394. Cited in: PubMed; PMID 21744734.

Zhu H, Deng FY, Mo XB, Qiu YH, Lei SF. Pharmacogenetics and pharmacogenomics for rheumatoid arthritis responsiveness to methotrexate treatment: the 2013 update. Pharmacogen. [Internet]. 2014; 15(4):551–566. doi: https://doi.org/f527cz

Cetinkaya A, Bulbuloglu E, Kurutas EB, Kantarceken B. N–acetylcysteine ameliorates methotrexate–induced oxidative liver damage in rats. Med. Sci. Monit. [Internet]. 2006 [cited 25 June 2023]; 12(8):BR274–278. Available in: https://bit.ly/3tQVZWH.

Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High–Dose Methotrexate. Oncol. [Internet]. 2016; 21(12):1471–1482. doi: https://doi.org/f9jsmp

Mahmoud AM, Hozayen WG, Ramadan SM. Berberine ameliorates methotrexate–induced liver injury by activating Nrf2/HO–1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. Biomed. Pharmacother. [Internet]. 2017; 94:280–291. doi: https://doi.org/gcpvm9

Kilic S, Emre S, Metin A, Isikoglu S, Erel O. Effect of the systemic use of methotrexate on the oxidative stress and paraoxonase enzyme in psoriasis patients. Arch. Dermatol. Res. [Internet]. 2013; 305(6):495–500. doi: https://doi.org/f459cj

Herrera B, Fernández M, Alvarez AM, Roncero C, Benito M, Gil J, Fabregat I. Activation of caspases occurs downstream from radical oxygen species production, Bcl–xL down–regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes. Hepatol. [Internet]. 2001; 34(3):548–556. doi: https://doi.org/bjsmbt

El–Gowilly SM, Helmy MM, El–Gowelli HM. Pioglitazone ameliorates methotrexate–induced renal endothelial dysfunction via amending detrimental changes in some antioxidant parameters, systemic cytokines and Fas production. Vascul. Pharmacol. [Internet]. 2015; 74:139–150. doi: https://doi.org/f73vg7

Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al–Omran M, Teoh H, Verma S. Adropin is a novel regulator of endothelial function. Circulat. [Internet]. 2010; 122(Supl. 11):S185–S192. doi: https://doi.org/fnqr5s

Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. [Internet]. 2008; 8(6):468–481. doi: https://doi.org/fjjq6d.

Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, Sahin I, Kocaman N, Citil C, Kendir Y. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin–induced diabetes. Mol. Cell Biochem. [Internet]. 2013; 380(1–2):73–81. doi: https://doi.org/f488sm

Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S. Plasma adropin levels predict endothelial dysfunction like flow–mediated dilatation in patients with type 2 diabetes mellitus. J. Investig. Med. [Internet]. 2013; 61(8):1161–1164. doi: https://doi.org/f5qkrk

Yu HY, Zhao P, Wu MC, Liu J, Yin W. Serum adropin levels are decreased in patients with acute myocardial infarction. Regul. Pept. [Internet]. 2014; 190–191:46–9. doi: https://doi.org/f58vcp

Cermik H, Taslipinar MY, Aydin I, Agilli M, Aydin FN, Ucar F, Alp BF, Toygar M, Ozkan E, Altayli E, Cayci T. The relationship between N–acetylcysteine, hyperbaric oxygen, and inflammation in a rat model of acetaminophen–induced nephrotoxicity. Inflammation. [Internet]. 2013; 36(5):1145–1152. doi: https://doi.org/f5ck4c

Asci H, Ozmen O, Ellidag HY, Aydin B, Bas E, Yilmaz N. The impact of gallic acid on the methotrexate–induced kidney damage in rats. J. Food Drug Anal. [Internet]. 2017; 25(4):890–897. doi: https://doi.org/mb9p

Demircan S, Onalan E, Kuloğlu T, Aydın S, Yalçın MH, Gözel N, Dönder E. Effects of vitamin D on apoptosis and betatrophin in the kidney tissue of experimental diabetic rats. Acta Biomed. [Internet]. 2020; 91(4):e2020089. doi: https://doi.org/mb9q

Kuloglu T, Aydin S. Immunohistochemical expressions of adropin and ınducible nitric oxide synthase in renal tissues of rats with streptozotocin–induced experimental diabetes. Biotech. Histochem. [Internet]. 2014; 89(2):104–110. doi: https://doi.org/gm2qdk

Heidari R, Ahmadi A, Mohammadi H, Ommati MM, Azarpira N, Niknahad H. Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate–induced renal injury and electrolytes imbalance. Biomed. Pharmacother. [Internet]. 2018; 107:834–840. doi: https://doi.org/gfcfxw

Kolli VK, Abraham P, Isaac B, Selvakumar D. Neutrophil infiltration and oxidative stress may play a critical role in methotrexate–induced renal damage. Chemother.. [Internet]. 2009; 55(2):83–90. doi: https://doi.org/c7xkhg

Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N–acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin. Biol. Ther. [Internet]. 2008; 8(12):1955–1962. doi: https://doi.org/dbkck6

Cetinkaya A, Kurutas EB, Bulbuloglu E, Kantarceken B. The effects of N–acetylcysteine on methotrexate–induced oxidative renal damage in rats. Nephrol. Dial Transplant. [Internet]. 2007; 22(1):284–285. doi: https://doi.org/dg445h

Mahmoud AM, Germoush MO, Al–Anazi KM, Mahmoud AH, Farah MA, Allam AA. Commiphora molmol protects against methotrexate–induced nephrotoxicity by up–regulating Nrf2/ARE/HO–1 signaling. Biomed. Pharmacother. [Internet]. 2018; 106:499–509. doi: https://doi.org/gd6nvm

Chen T, Wang Q, Cui J, Yang W, Shi Q, Hua Z, Ji J, Shen P. Induction of apoptosis in mouse liver by microcystin–LR: a combined transcriptomic, proteomic, and simulation strategy. Mol. Cell Proteomics. [Internet]. 2005; 4(7):958–974. doi: https://doi.org/dvwrdt

McClain DE, Kalinich JF, Ramakrishnan N. Trolox inhibits apoptosis in irradiated MOLT–4 lymphocytes. FASEB J. [Internet]. 1995; 9(13):1345–1354. doi: https://doi.org/mb9t

Yang C, DeMars KM, Hawkins KE, Candelario–Jalil E. Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia–like conditions. Peptides. [Internet]. 2016; 81:29–37. doi: https://doi.org/f8qf82

Yang C, DeMars KM, Candelario–Jalil E. Age–Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthase and Increased Oxidative Stress in the Rat Brain. Aging Dis. [Internet]. 2018; 9(2):322–330 doi: https://doi.org/mb9v

Chen X, Xue H, Fang W, Chen K, Chen S, Yang W, Shen T, Chen X, Zhang P, Ling W. Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity. Redox Biol. [Internet]. 2019; 21:101068. doi: https://doi.org/mb9w

Published
2024-01-13
How to Cite
1.
Ahmet K, Tuncay K, Can AT, Ahmet K, Tunc O, Osman V, Irfan O, Emel SK. Evaluating Adropine levels in kidney tissue after Methotrexate treatment in rats: a prospective experimental study. Rev. Cient. FCV-LUZ [Internet]. 2024Jan.13 [cited 2024May14];34(1):7. Available from: https://www.produccioncientificaluz.org/index.php/cientifica/article/view/41475
Section
Veterinary Medicine