Theraupeutic potency of benfotiamine against methotrexate-induced kidney injury and irisin immunoreactivity

Abstract

Amaç: Benfotiamine (BFT), antioksidatif etkilere sahip etkili bir ajandır. Bu çalışmada, BFT'nin metotreksat (MTX) kaynaklı böbrek hasarı ve irisinin immünoreaktivitesi üzerindeki etkileri araştırılmıştır. Yöntem: Toplam 28 sıçan dört eşit gruba ayrıldı: Kontrol (herhangi bir tedavi uygulanmadı), BFT (50 mg / kg BFT oral gavaj ile verildi), MTX (20 mg / kg MTX intraperitoneal yolla verildi) ve MTX + BFT. Çalışmanın sonunda, alınan böbrek dokuları rutin histolojik takip serilerinden geçirildi ve parafin bloklara gömüldü. Histopatolojik inceleme için hematoksilen & eozin, irisin ve kaspaz 3 için streptavidin-biotin-peroksidaz kompleks yöntemi parafin bloklardan alınan kesitlere uygulandı. Toplam antioksidan seviyesi (TAS) ve toplam oksidan seviyesi (TOS) Rel Assay kitleri ile belirlendi. Bulgular: MTX'in histopatolojik hasara, irisin ve kaspaz-3 immünoreaktivitesinde önemli bir artışa neden olduğu gözlendi. Biyokimyasal olarak, MTX verilen hayvanlarda toplam oksidan seviyesinde (TOS) önemli artış ve toplam antioksidan seviyesinde (TAS) düşüş belirlendi. BFT tedavisinin histopatolojik hasarı iyileştirdiği, TOS ve kaspaz-3 immünoreaktivitesini önemli ölçüde azalttığı, TAS düzeylerini artırdığı ve irisin immünoreaktivitesini önemsiz ölçüde azalttığı bulundu. Sonuç: Sonuç olarak BFT, MTX'in neden olduğu böbrek hasarını önlemede koruyucu etkiler sergilemiştir.

References

1. Akbulut, S., Elbe, H., Eris, C., et al., 2014. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats. World J Gastroenterol. 20:10158-10165.
2. Asvadi, I., Hajipour, B., Asvadi, A., et al., 2011. Protective effect of pentoxyfilline in renal toxicity after methotrexate administration. Eur Rev Med Pharmacol Sci. 15:1003-1009.
3. Aydin S. 2014. Three new players in energy regulation: preptin, adropin and irisin. Peptides. 56:94-110.
4. Bello SO, Chika A. 2009. Dose-dependent amelioration of gentamicin-induced nephrotoxicity in adult swiss albino rats by vitamin B-complex - a preliminary study. Trop J Pharm Res. 8.
5. Bosma, M., Gerling, M., Pasto, J., et al., 2016. FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice. Nat Commun. 7:11314.
6. Bostrom, P., Wu, J., Jedrychowski, MP., et al., 2012. A PGC1α-dependent myokine that drives browning of white fat and thermogenesis. Nature. 481:463-468.
7. Bozic, I., Savic, D., Stevanovic, I., et al., 2015. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells. Front Cell Neurosci. 9:351.
8. Bozkurt, M., Em, S., Oktayoglu, P., et al., 2014. Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats. Clin Investig Med Med Clin Exp. 37:E19-25.

9. Chabner BA, Longo L (Eds.) 2010. Cancer Chemotherapy and Biotherapy: Principles and Practice, Fifth edition. ed. LWW, Philadelphia.
10. Deng, X., Huang, W., Peng, J., et al., 2018. Irisin alleviates advanced glycation end products-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling. Inflammation. 41:260-275.
11. Dhir, S,, Tarasenko, M., Napoli, E., et al., 2019. Neurological, psychiatric and biochemical aspects of thiamine deficiency in children and adults. Front Psychiatry. 10: 207.
12. Ebert, T., Focke, D., Petroff, D., et al., 2014. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol. 170:501-506. El-Sheikh, AA., Morsy, MA., Abdalla, AM., et al., 2015. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm. 20151-12.
13. Erdogan MA, Yalcin A. 2018. Protective effects of benfotiamine on irisin activity in methotrexate-induced liver injury in rats. Arch Med Sci. 14. https://doi.org/10.5114/aoms.2018.80002.
14. Erel O. 2005. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 38:1103-1111.
15. Erel O. 2004. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 37: 277-285.
16. Fan, X., Du, J., Wang, MH., et al., 2019. Irisin contributes to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion. Oxid Med Cell Longev. 7857082.
17. Ferguson, MA., Vaidya, VS., Bonventre, JV., 2008. Biomarkers of nephrotoxic acute kidney injury. Toxicology. 245:182-193. Frank T, Bitsch R, Maiwald J, et al., 2000. High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine. Eur J Clin Pharmacol. 56:251-257.
18. Gadau, S., Emanueli, C., Van Linthout S., et al., 2006. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia. 49:405-420. Gouveia, MC., Vella, JP., Cafeo, FR., et al., 2016. Association between irisin and major chronic diseases: a review. Eur Rev Med Pharmacol Sci. 20: 4072-4077.
19. Hafez, HM., Ibrahim, MA., Ibrahim, SA., et al., 2015. Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats. Eur J Pharmacol. 768:1-12.
20. Harisa GI. 2013. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats. J Biochem Mol Toxicol. 27:398-405.
21. Heidari, R., Ahmadi, A., Mohammadi, H., et al., 2018.Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance. Bıomed Pharmacother.107:834-840.
22. Herman, S., Zurgil, N., Deutsch, M. 2005. Low dose methotrexate induces apoptosis with reactive oxygen species involvement in T lymphocytic cell lines to a greater extent than in monocytic lines. Inflamm Res. 54:273-280.
23. Hernandez-Vazquez, ADJ., Garcia-Sanchez, JA., Moreno-Arriola, E., et al., 2016.Thiamine deprivation produces a liver ATP deficit and metabolic and genomic effects in mice: Findings are parallel to those of biotin deficiency and have implications for energy disorders. J Nutr Nutr. 9:287-299.
24. Jahovic, N., Cevik, H., Sehirli, AO., et al., 2003. Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. J Pineal Res. 34:282-287.
25. Jo, SK., Yun, SY., Chang, KH., et al., 2001. Alpha-MSH decreases apoptosis in ischaemic acute renal failure in rats: possible mechanism of this beneficial effect. Nephrol Dial Transplant. 16:1583-1591.
26. Jung, KH., Lee, JH., Park, JW., et al., 2014. Annexin V imaging detects diabetes-accelerated apoptosis and monitors the efficacy of benfotiamine treatment in ischemic limbs of mice. Mol Imaging. 13:7290-2014.
27. Keles H, Yalcin A, Aydin H. 2019. Protective effect of vitamin D on imidacloprid-induced testicular injury in rats. Arch Med Sci. 15. https://doi.org/10.5114/aoms.86776.
28. Kolli, VK., Abraham, P., Isaac, B., et al., 2009. Neutrophil infiltration and oxidative stress may play a critical role in methotrexate-induced renal damage. Chemotherapy. 55:83-90.
29. Kuloglu T, Aydin S. 2014. Immunohistochemical expressions of adropin and ınducible nitric oxide synthase in renal tissues of rats with streptozotocin-ınduced experimental diabetes. Biotech Histochem. 89:104–110.
30. Lu, J., Xiang, G., Liu, M., et al., 2015. Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-Null diabetic mice. Atherosclerosis. 243:438-448.
31. Manzardo, AM., He, J., Poje, A., et al., 2013. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence. Drug Alcohol Depen. 133:562-570.
32. Mazur-Bialy, AI., Kozlowska, K., Pochec, E., et al., 2018. Myokine irisin-induced protection against oxidative stress in vitro. Involvement of heme oxygenase-1 and antioxidazing enzymes superoxide dismutase-2 and glutathione peroxidase. J Physiol Pharmacol. 69:117-125.
33. Morsy, MA., Ibrahim, SA., Amin, EF.,et al., 2013. Curcumin ameliorates methotrexate-induced nephrotoxicity in rats. Adv Pharmacol Sci. 387071.
34. Pan, X., Chen, Z., Fei, G., et al., 2016. Long-term cognitive improvement after benfotiamine administration in patients with Alzheimer’s disease. Neuroscı Bull. 32:591-596.
35. Park, KH., Zaichenko, L., Brinkoetter, M., et al., 2013. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab. 98:4899-4907.
36. Patil, MM., Parameswaran, S., Kamalanathan, S., et al., 2018. The effect of hypothyroidism on serum irisin level in patients with nondiabetic chronic kidney disease: A pilot study with a cross-sectional design. Saudi J Kidney Dis Transplant. 29:911-915.
37. Provatopoulou, X., Georgiou, GP., Kalogera, E., et al., 2015. Serum irisin levels are lower in patients with breast cancer: association with disease diagnosis and tumor characteristics. BMC Cancer. 15:898.
38. Raj, V., Ojha, S., Howarth, FC., et al., 2018. Therapeutic potential of benfotiamine and its molecular targets. Eur Rev Med Pharmacol Sci. 22:3261–3273.
39. Rizk, FH., Elshweikh, SA., Abd El-Naby, AY. 2016. Irisin levels in relation to metabolic and liver functions in Egyptian patients with metabolic syndrome. Can J Physiol Pharmacol. 94:359-362.
40. Sarioglu, G., Korkmaz, H., Onalan, E., et al., 2016. Irisin levels increase during experimentally induced acute myocardial infarction. Curr Res Cardiol. 3:9-12.
41. Schmid, U., Stopper, H., Heidland, A., et al., 2008. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes Metab Res Rev. 24:371-377.
42. Schupp, N., Dette, EM., Schmid, U., et al., 2008. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients. Naunyn Schmiedebergs Arch Pharmacol. 378:283-291.
43. Shen S, O’Brien T, Yap LM, Prince HM, McCormack CJ. 2012. The use of methotrexate in dermatology: a review. Australas J Dermatol. 53:1-18.
44. Shoeb, M., Ramana, KV. 2012. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. Free Radic Biol.Med. 52:182-190.
45. Tabassum, H., Parvez, S., Pasha, ST.,et al., 2010. Protective effect of lipoic acid against methotrexate-induced oxidative stress in liver mitochondria. Food Chem Toxicol. 48:1973-1979.
46. Üçkardeş, F, Aslan, E, Küçükönder, H. 2013. A fast approach to select the appropriate test statistics. Akad Ziraat Derg. 2:55–61. Ulusoy, HB., Öztürk, İ., Sönmez, MF. 2016. Protective effect of propolis on methotrexate-induced kidney injury in the rat. Ren Fail. 38:744-750.
47. Ustuner, MA., Kaman, D., Colakoglu, N. 2017. Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin. Tissue Cell. 49:691-696.
48. Vardi, N., Parlakpinar, H., Cetin A., et al., 2010. Protective effect of β-carotene on methotrexate–induced oxidative liver damage. Toxicol Pathol. 38:592-597.
49. Wang, H., Zhao, YT., Zhang, S., et al., 2017. Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury. J Cell Physiol. 232:3775-3785.
50. Widemann, BC., Adamson, PC. 2006. Understanding and managing methotrexate nephrotoxicity. The Oncologist. 11:694-703.
51. YALÇIN, A., PEKMEZ, H. 2020. Black carrot juice: A new approach to cure acrylamide-induced hepatotoxicity in rats. Ankara Sağlık Bilimleri Dergisi, 9(1), 207-216.
52. Yilmaz, I., Demiryilmaz, I., Turan MI, et al., 2015. The effects of thiamine and thiamine pyrophosphate on alcohol-induced hepatic damage biomarkers in rats. Eur Rev Med Pharmacol Sci. 19:664-70.
53. Zhang, Y., Li, R., Meng, Y., et al., 2014. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 63:514-525.
54. Zhu D, Wang H, Zhang J, et al., 2015. Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses. J Mol Cell Cardiol. 87:138-147.