سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Mahdavifard, Sina, Hasani, Amir. (1404). Anti-obesity and hepatoprotective effects of pyridoxal phosphate in rats with metabolic syndrome by raising anti-oxidant potential in both serum and liver tissue, while also decreasing hepatic nuclear factor expression. , 28(8), 1012-1018. doi: 10.22038/ijbms.2025.81836.17702
Sina Mahdavifard; Amir Hasani. "Anti-obesity and hepatoprotective effects of pyridoxal phosphate in rats with metabolic syndrome by raising anti-oxidant potential in both serum and liver tissue, while also decreasing hepatic nuclear factor expression". , 28, 8, 1404, 1012-1018. doi: 10.22038/ijbms.2025.81836.17702
Mahdavifard, Sina, Hasani, Amir. (1404). 'Anti-obesity and hepatoprotective effects of pyridoxal phosphate in rats with metabolic syndrome by raising anti-oxidant potential in both serum and liver tissue, while also decreasing hepatic nuclear factor expression', , 28(8), pp. 1012-1018. doi: 10.22038/ijbms.2025.81836.17702
Mahdavifard, Sina, Hasani, Amir. Anti-obesity and hepatoprotective effects of pyridoxal phosphate in rats with metabolic syndrome by raising anti-oxidant potential in both serum and liver tissue, while also decreasing hepatic nuclear factor expression. , 1404; 28(8): 1012-1018. doi: 10.22038/ijbms.2025.81836.17702

Anti-obesity and hepatoprotective effects of pyridoxal phosphate in rats with metabolic syndrome by raising anti-oxidant potential in both serum and liver tissue, while also decreasing hepatic nuclear factor expression

Iranian Journal of Basic Medical Sciences
مقاله 4، دوره 28، شماره 8، آبان 2025، صفحه 1012-1018    اصل مقاله (323.15 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.81836.17702
نویسندگان
Sina Mahdavifard* 1، 2؛ Amir Hasani1
1Department of Clinical Biochemistry, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
2Department of Biochemistry and Genetics, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
چکیده
Objective(s): Insulin resistance is the primary trigger of metabolic syndrome, carbonyl stress, and vitamin B6 deficiency, while the nuclear factor (NF-κB) pathway is a pivotal factor in its development. Hence, we investigated the impact of pyridoxal phosphate (PLP) on liver and kidney functions, carbonyl stress, and inflammatory markers in serum and liver tissue.
Materials and Methods: The study involved four groups of rats, each consisting of eight rats: untreated normal rats (N), rats induced to have metabolic syndrome (MetS), and rats treated with PLP, labeled as N (PLP) and MetS (PLP), respectively. Metabolic syndrome was induced in rats by administering a concentrated sucrose solution for four months. The treated groups received daily PLP at 180 mg/l in their drinking water. Subsequently, the metabolic profile, NF-κB expression, indicators of gly-oxidation, inflammation, and organ function markers were evaluated. 
Results: PLP significantly reduced gly-oxidation, carbonyl stress, and inflammatory indicators (in both serum and liver tissue) as well as NF-κB expression, glycation, carbonyl stress, liver fat levels, glycemia, insulin resistance, and body weight (P<0.001). The treatment also prevented acute hepatitis. 
Conclusion: PLP had beneficial effects in the metabolic syndrome rat model, showing anti-obesity and hepato-renal protective effects. It improved metabolism and organ (liver and kidney) functions by modulating NF-κB expression, glutathione metabolism, carbonyl stress, and oxidative stress.
کلیدواژه‌ها
Glutathione؛ Insulin resistance؛ Metabolic syndrome؛ NF-kappa B؛ Pyridoxal phosphate
مراجع
1. Ribeiro PVM TJ, Costa MAC, Mattar JB, Alfenas RCG. Effect of reducing dietary advanced glycation end products on obesity-associated complications: a systematic review. Nutr Rev 2019; 77:725-734. 
2. Huang CJ, McAllister MJ, Slusher AL, Webb HE, Mock JT, Acevedo EO. Obesity-related oxidative stress: The impact of physical activity and diet manipulation. Sports Med Open 2015; 1:32-44. 
3. Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M. Metabolic syndrome: updates on pathophysiology and management in 2021. Int J Mol Sci 2022; 23:786-794. 
4. Gehrke N, Schattenberg JM. Metabolic inflammation-a role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease? Gastroenterology 2020; 158:1929-1947. 
5. Ribeiro PVM TJ, Costa MAC, Mattar JB, Alfenas RCG. Effect of reducing dietary advanced glycation end products on obesity-associated complications: A systematic review. Nutr Rev 2019; 77:725-734. 
6. Inagi R. RAGE and glyoxalase in kidney disease. Glycoconj J 2016; 33:619-626. 
7. Nigro C, Leone A, Raciti GA, Longo M, Mirra P, Formisano P, et al. Methylglyoxal-glyoxalase 1 balance: The root of vascular damage. Int J Mol Sci 2017; 18:188-202. 
8. Zhang D LX, Liu Y, Sun X, Wang B, Ren Y, Zhao Y, Zhou J, Han C, Yin L, et al. 2017. Leisure-time physical activity and incident metabolic syndrome: A systematic review and dose-response metaanalysis of cohort studies. Metabolism 2017; 75:36-44. 
9. Zhu J, Chen C, Lu L, Shikany JM, D’Alton ME, Kahe K. Folate, vitamin B6, and vitamin B12 status in association with metabolic syndrome incidence. JAMA Netw Open 2023; 6:2250621-2250633. 
10. Mascolo E, Vernì F. Vitamin B6 and diabetes: Relationship and molecular mechanisms. Int J Mol Sci 2020; 21:3669-3688. 
11. Souza Cruz EM, Bitencourt de Morais JM. Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats. Biol Open 2020; 9:47282-47290. 
12. Kopruszinski CM, Reis RC, Chichorro JG. B vitamins relieve neuropathic pain behaviors induced by infraorbital nerve constriction in rats. Life Sci 2012; 91:1187-1195. 
13. Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T. Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol Dial Transplant 2007; 22:2165-2174. 
14. Xu YJ, Wu XQ, Liu W, Lin XH, Chen JW, He R. A convenient assay of glycoserum by nitroblue tetrazolium with iodoacetamide. Clin Chim Acta 2002; 325:127-131. 
15. Cohen MP, Shea EA, Wu VY. Inhibiting low-density lipoprotein glycation ameliorates increased cholesteryl ester synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats. Metabolism 2010; 59:658-663. 
16. Pappalardo M, Pappalardo L, Brooks P. Rapid and reliable HPLC method for the simultaneous determination of dihydroxyacetone, methylglyoxal and 5-hydroxymethylfurfural in leptospermum honeys. PLoS One 2016; 11:167006-1670015. 
17. Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res 2002; 51:597-604. 
18. Skapare E, Konrade I, Liepinsh E, Makrecka M, Zvejniece L, Svalbe B, et al. Glyoxalase 1 and glyoxalase 2 activities in blood and neuronal tissue samples from experimental animal models of obesity and type 2 diabetes mellitus. J Physiol Sci 2012; 62:469-478. 
19. D’souza D SB, Shetty SR, Balan P. Estimation of serum malondialdehyde in potentially malignant disorders and post-anti-oxidant treated patients: A biochemical study. Contemp Clin Dent 2012; 4:448-451. 
20. Taylor EL, Armstrong KR, Perrett D, Hattersley AT, Winyard PG. Optimisation of an advanced oxidation protein products assay: It’s application to studies of oxidative stress in diabetes mellitus. Oxid Med Cell Longev 2015; 2015:496271-496281. 
21. Ahotupa M, Marniemi J, Lehtimäki T, Talvinen K, Raitakari OT, Vasankari T, Viikari JLJ, Ylä-Herttuala S. Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL oxidation. Clin Biochem 1998; 31:257-261. 
22. Esterbauer H, Gebicki J, Puhl H, Jürgens G. The role of lipid peroxidation and anti-oxidants in oxidative modification of LDL. Free Radic Biol Med 1992; 13:341–390. 
23. Begic A, Djuric A, Gobeljic B, Stevanovic I, Lukic V, Stanojevic I, et al. The simple isocratic HPLC— UV method for the simultaneous determination of reduced and oxidized glutathione in animal tissue. Acta Chromatographica 2017; 29:67-84. 
24. Ceron JJ, Tecles F, Tvarijonaviciute A. Serum paraoxonase 1 (PON1) measurement: An update. BMC Vet Res 2014; 10:74-83. 
25. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121-126. 
26. Rao X HX, Zhou Z, Lin X. An improvement of the 2ˆ (-delta delta CT) method for quantitative realtime polymerase chain reaction data analysis. Biostat Bioinforma Biomath 2013; 3:71-85. 
27. Souza Cruz EM BdMJ, Dalto da Rosa CV, da Silva Simões M, Comar JF, de Almeida Chuffa LG, et al. Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats. Biol Open 2020; 9:1-10. 
28. Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X, Bouzas C, Mateos D, Pons A, Tur JA, Sureda A. Metabolic syndrome is associated with oxidative stress and proinflammatory state. Antioxidants 2020; 9:236-242. 
29. Okura T, Ueta E, Nakamura R, Fujioka Y, Sumi K, Matsumoto K, et al. High serum advanced glycation end products are associated with decreased insulin secretion in patients with type 2 diabetes: A brief report. J Diabetes Res 2017; 2017:5139750-5139763. 
30. Zhu J CC, Lu L, Shikany JM, D’Alton ME, Kahe K. Folate, vitamin B6, and vitamin B12 status in association with metabolic syndrome incidence. JAMA Netw Open 2023;6: 2250621-2250636 
31. Mahdavifard S, Dehghani R, Jeddi F, Najafzadeh N. Thiamine reduced metabolic syndrome symptoms in rats via down-regulation of hepatic nuclear factor-kβ and induction activity of glyoxalase-I. Iran J Basic Med Sci 2021; 24:293-299. 
32. Kleniewska P, Piechota-Polanczyk A, Michalski L, Michalska M, Balcerczak E, Zebrowska M, et al. Influence of block of NF-kappa B signaling pathway on oxidative stress in the liver homogenates. Oxid Med Cell Longev 2013; 2013:308358-308369. 
33. Santel T, Pflug G, Hemdan NY, Schäfer A, Hollenbach M, Buchold M, et al. Curcumin inhibits glyoxalase 1: A possible link to its anti-inflammatory and anti-tumor activity. PLoS One 2008;3: 3508-3521. 
34. Liao BC, Hsieh CW, Lin YC, Wung BS. The glutaredoxin/glutathione system modulates NF-kappaB activity by glutathionylation of p65 in cinnamaldehyde-treated endothelial cells. Toxicol Sci 2010; 116:151-163. 
35. Gao D MM, Ding C, Fok M, Steele T, Ford C, et al. Interleukin-1beta mediates macrophage induced impairment of insulin signaling in human primary adipocytes. Am J Physiol Endocrinol Metab 2014; 307:289-304. 
36. Piuri G, Basello K, Rossi G, Soldavini CM, Duiella S, Privitera G, et al. Methylglyoxal, glycated albumin, PAF, and TNF-α: Possible inflammatory and metabolic biomarkers for management of gestational diabetes. Nutrients 2020; 12:479-491. 
37. Demir M, Sert S, Kaleli I, Demir S, Cevahir N, Yildirim U, et al. Liver lipid peroxidation in experimental Escherichia coli peritonitis: The role of myeloperoxidase and nitric oxide inhibition. Med Sci Monit 2007; 13: 225-229. 
38. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nature medicine 2005; 11:183-190. 
39. Khoury T, Ya’acov AB, Shabat Y, Zolotarovya L, Snir R, Ilan Y. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance. World J Gastroenterol 2015; 21:7443–7456. 
40. Mitrovic B GZ, Obradovic M, Radunovic M, Rizzo M, Banach M, Isenovic ER. Non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes mellitus: Where do we stand today? Arch Med Sci 2023; 19:884-894. 
41. Chai W, Aylor K, Liu Z, Gan LM, Michaëlsson E, Barrett E. Inhibiting myeloperoxidase prevents onset and reverses established high-fat diet-induced microvascular insulin resistance. Am J Physiol Endocrinol Metab 2019; 317: 1063-1069.
42. Uribarri J, Cai W, Woodward M, Tripp E, Goldberg L, Pyzik R, et al. Elevated serum advanced glycation endproducts in obese indicate risk for the metabolic syndrome: a link between healthy and unhealthy obesity? J Clin Endocrinol Metab 2015; 100:1957-1966. 
43. Piuri G, Basello K, Rossi G, Soldavini ChM, Duiella S, Privitera G, et al. Methylglyoxal, glycated albumin, paf, and tnf-α: Possible inflammatory and metabolic biomarkers for management of gestational diabetes. Nutrients 2020; 12:12-27. 
44. Khalid M, Alkaabi J, Khan MAB, Adem A. Insulin signal transduction perturbations in insulin resistance. Int J Mol Sci 2021; 22:8590-8607. 
45. Zhang Y ZX, Liu C, Shen Q, Wu Y. Vitamin B6 inhibits high glucose-induced islet β cell apoptosis by upregulating autophagy. Metabolites 2022; 12:1048-1062. 
46. Amarnath V, Amarnath K, Amarnath K, Davies S, Roberts LJ 2nd. Pyridoxamine: An extremely potent scavenger of 1, 4-dicarbonyls. Chem Res Toxicol 2004; 17:410–415. 
47. Zhang Y, Zhou XA, Liu C, Shen Q, Wu Y. Vitamin B6 inhibits high glucose-induced islet β cell apoptosis by upregulating autophagy. Metabolites 2022; 12:1048-1062. 
48. Gurgul-Convey E, Mehmeti I, Plötz T, Jörns A, Lenzen S. Sensitivity profile of the human EndoC-betaH1 beta cell line to proinflammatory cytokines. Diabetologia 2016; 59:2125–2133. 
49. Liu Z, Li P, Zhao ZH, Zhang Y, Ma ZM, Wang SX. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in apoe (-/-) mice fed with high-fat diet. J Diabetes Res 2016; 2016:1748065-1748073. 
50. Taysi S. Oxidant/antioxidant status in liver tissue of vitamin B6 deficient rats. Clin Nutr 2005; 24:385-389. 
51. Zhang Q, Zhang DL, Zhou XL, Li Q, He N, Zhang J, et al. Antihyperlipidemic and hepatoprotective properties of vitamin B6 supplementation in rats with high-fat diet-induced hyperlipidemia. Endocr Metab Immune Disord Drug Targets 2021; 21:2260-2272. 
52. Haidari F, Mohammadshahi M, Zarei M, Haghighizadeh MH, Mirzaee F. The effect of pyridoxine hydrochloride supplementation on leptin, adiponectin, glycemic indices, and anthropometric indices in obese and overweight women. Clin Nutr Res 2021; 10:230-242. 
53. Vasdev S, Ford CA, Parai S, Longerich L, Gadag V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol Cell Biochem 1999; 200:155-162. 

آمار
تعداد مشاهده مقاله: 59
تعداد دریافت فایل اصل مقاله: 74