سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Sanajou, Davoud, Bahram Beigi, Saman, Aslani, Somayeh. (1400). β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway. , 24(5), 650-656. doi: 10.22038/ijbms.2021.55565.12422
Davoud Sanajou; Saman Bahram Beigi; Somayeh Aslani. "β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway". , 24, 5, 1400, 650-656. doi: 10.22038/ijbms.2021.55565.12422
Sanajou, Davoud, Bahram Beigi, Saman, Aslani, Somayeh. (1400). 'β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway', , 24(5), pp. 650-656. doi: 10.22038/ijbms.2021.55565.12422
Sanajou, Davoud, Bahram Beigi, Saman, Aslani, Somayeh. β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway. , 1400; 24(5): 650-656. doi: 10.22038/ijbms.2021.55565.12422

β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway

Iranian Journal of Basic Medical Sciences
مقاله 12، دوره 24، شماره 5، مرداد 2021، صفحه 650-656    اصل مقاله (817.23 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2021.55565.12422
نویسندگان
Davoud Sanajou1؛ Saman Bahram Beigi1؛ Somayeh Aslani* 1، 2
1Department of Biochemistry, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Biochemistry, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
چکیده
Objective(s): β-LAPachone (B-LAP) is a natural product with established anti-inflammatory properties. In this study, we investigated the protective potential of B-LAP against diabetic nephropathy in streptozotocin (STZ) induced diabetic mice.
Materials and Methods: Diabetes induction in mice was carried out by a single intraperitoneal injection of STZ. 2.5 mg/kg/day and 5 mg/kg/day doses of B-LAP were administered orally for twelve weeks and renal histoarchitecture, caspase-3, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), glutathione peroxidase (GPX), as well as urinary nephrin and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Additionally, kidney levels of PI3K, phosphorylated (p)-Akt, p-mTOR, p-CREB, and SIRT1 were assessed in the present investigation.
Results: 5 mg/kg B-LAP significantly decreased urinary excretions of nephrin and NGAL. It also mitigated renal TNF-α and MDA levels and simultaneously improved GPX activities. 5 mg/kg B-LAP improved renal function in diabetic mice as indicated by elevated values of creatinine clearance. While B-LAP elevated renal levels of SIRT1, it alleviated PI3K, p-Akt, p-mTOR, and p-CREB levels in the kidneys of diabetic mice.
Conclusion: Collectively, these findings suggest B-LAP as a potential renoprotective agent in STZ-induced diabetic mice probably via modulating the PI3K/Akt/mTOR pathway.
کلیدواژه‌ها
Akt؛ β-LAPachone؛ Diabetic nephropathy؛ mTOR؛ PI3K
مراجع
1. Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 2005; 16:S30-S33.
2. Mahfoz AM, El-Latif HAA, Ahmed LA, Hassanein NM, Shoka AA. Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:1315-1324.
3. Tahara A, Takasu T. Prevention of progression of diabetic nephropathy by the SGLT2 inhibitor ipragliflozin in uninephrectomized type 2 diabetic mice. Eur J Pharmacol 2018; 830:68-75.
4. Sanajou D, Ghorbani Haghjo A, Argani H, Aslani S. AGE-RAGE axis blockade in diabetic nephropathy: Current status and future directions. Eur J Pharmacol 2018; 833:158-164.
5. Heerspink HJ, De Zeeuw D. Novel anti-inflammatory drugs for the treatment of diabetic kidney disease. Diabetologia 2016; 59:1621-1623.
6. Moon D-O, Choi YH, Kim N-D, Park Y-M, Kim G-Y. Anti-inflammatory effects of β-lapachone in lipopolysaccharide-stimulated BV2 microglia. Int Immunopharmacol 2007; 7:506-514.
7. Lee J-s, Park AH, Lee S-H, Lee S-H, Kim J-H, Yang S-J, et al. Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice. PLoS One 2012; 7:e47122.
8. Mann JF, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017; 377:839-848.
9. Sanajou D, Haghjo AG, Argani H, Roshangar L, Rashtchizadeh N, Ahmad SNS, et al. Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat. Eur J Pharmacol 2019; 842:40-48.
10. Ashrafi Jigheh Z, Ghorbani Haghjo A, Argani H, Roshangar L, Rashtchizadeh N, Sanajou D, et al. Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis. Iran J Basic Med Sci 2019; 22:384-390.
11. Sanajou D, Ahmad SNS, Hosseini V, Kalantary-Charvadeh A, Marandi Y, Roshangar L, et al. β-Lapachone protects against doxorubicin-induced nephrotoxicity via NAD+/AMPK/NF-kB in mice. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:633-640.
12. Jigheh ZA, Haghjo AG, Argani H, Roshangar L, Rashtchizadeh N, Sanajou D, et al. Empagliflozin attenuates renal and urinary markers of tubular epithelial cell injury in streptozotocin-induced diabetic rats. Indian J Clin Biochem 2020; 35:109-114.
13. Queiroz ML, Valadares MC, Torello CO, Ramos AL, Oliveira AB, Rocha FD, et al. Comparative studies of the effects of Tabebuia avellanedae bark extract and β-lapachone on the hematopoietic response of tumour-bearing mice. J Ethnopharmacol 2008; 117:228-235.
14. Wadie W, El-Tanbouly DM. Vinpocetine mitigates proteinuria and podocytes injury in a rat model of diabetic nephropathy. Eur J Pharmacol 2017; 814:187-195.
15. Chen C, Ju R, Zhu L, Li J, Chen W, Zhang D-c, et al. Carboxyamidotriazole alleviates muscle atrophy in tumor-bearing mice by inhibiting NF-κB and activating SIRT1. Naunyn Schmiedebergs Arch Pharmacol 2017; 390:423-433.
16. Ahmad SNS, Rashtchizadeh N, Argani H, Roshangar L, Ghorbani Haghjo A, Sanajou D, et al. Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity. Iran J Basic Med Sci 2019; 22:179-186.
17. Oh G-S, Kim H-J, Choi J-H, Shen A, Choe S-K, Karna A, et al. Pharmacological activation of NQO1 increases NAD+ levels and attenuates cisplatin-mediated acute kidney injury in mice. Kidney Int 2014; 85:547-560.
18. Ahmad SNS, Sanajou D, Kalantary‐Charvadeh A, Hosseini V, Roshangar L, Khojastehfard M, et al. β‐LAP achone ameliorates doxorubicin‐induced cardiotoxicity via regulating autophagy and Nrf2 signalling pathways in mice. Basic Clin Pharmacol Toxicol 2020; 126:364-373.
19. Inoki K. Role of TSC–mTOR pathway in diabetic nephropathy. Diabetes Res Clin Pract 2008; 82:S59-S62.
20. Donate-Correa J, Martín-Núñez E, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF. Inflammatory cytokines in diabetic nephropathy. J Diabetes Res 2015; 2015:948417.
21. Wu W, Hu W, Han W-B, Liu Y-L, Tu Y, Yang H-M, et al. Inhibition of Akt/mTOR/p70S6K signaling activity with Huangkui capsule alleviates the early glomerular pathological changes in diabetic nephropathy. Front Pharmacol 2018; 9:443-450.
22. Huang W-J, Fu Q, Xiao Y-H, Gong Q, Wu W-J, Shen Z-L, et al. Effect of Qufengtongluo decoction on PI3K/Akt signaling pathway in the kidney of type 2 diabetes mellitus rat with diabetic nephropathy. Evid Based Complement Alternat Med 2018; 2018: 8421979.
23. Habib SL, Mohan S, Liang S, Li B, Yadav M. Novel mechanism of transcriptional regulation of cell matrix protein through CREB. Cell Cycle 2015; 14:2598-2608.
24. Katoh Y, Itoh K, Yoshida E, Miyagishi M, Fukamizu A, Yamamoto M. Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription. Genes Cells 2001; 6:857-868.
25. Arany I, Megyesi JK, Reusch JE, Safirstein RL. CREB mediates ERK-induced survival of mouse renal tubular cells after oxidant stress. Kidney Int 2005; 68:1573-1582.
26. Visavadiya NP, Li Y, Wang S. High glucose up-regulates upstream stimulatory factor 2 in human renal proximal tubular cells through angiotensin II-dependent activation of CREB. Nephron Exp Nephrol 2011; 117:e62-e70.
27. Gonzalez AA, Liu L, Lara LS, Bourgeois CR, Ibaceta-Gonzalez C, Salinas-Parra N, et al. PKC-α-dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct. Am J Physiol Renal Physiol 2015; 309:F880-F888.
28. Kashihara N, Haruna Y, K Kondeti V, S Kanwar Y. Oxidative stress in diabetic nephropathy. Curr Med Chem 2010; 17:4256-4269.
29. Ahmad SNS, Rashtchizadeh N, Argani H, Roshangar L, Ghorbani Haghjo A, Sanajou D, et al. Dunnione protects against experimental cisplatin-induced nephrotoxicity by modulating NQO1 and NAD+ levels. Free Radic Res 2018; 52:808-817.
30. Huang K, Gao X, Wei W. The crosstalk between sirt1 and keap1/Nrf2/are anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF-β1 expressions in rat glomerular mesangial cells. Exp Cell Res 2017; 361:63-72.
31. Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M. Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy. Diabetes 2007; 56:2155-2160.
32. Sanajou D, Haghjo AG, Argani H, Roshangar L, Ahmad SNS, Jigheh ZA, et al. FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats. J Biochem Physiol 2018; 74:467-478.
33. Devarajan P. Neutrophil gelatinase-associated lipocalin: A promising biomarker for human acute kidney injury. Biomark Med 2010; 4:265-280.

آمار
تعداد مشاهده مقاله: 814
تعداد دریافت فایل اصل مقاله: 476