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Glutamine Defended the Kidneys Versus Lead Intoxication Via Elevating Endogenous Antioxidants, Reducing Inflammation and Carbonyl Stress, as well as Improving Insulin Resistance and Dyslipidemia

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Abstract

Kidneys are primarily sensitive to lead (Pb) poisoning due to their cardinal role in lead excretion. Then, we studied the effect of glutamine (Gln) on lead nephrotoxicity in rats by assessing the histopathological and biochemical parameters (the renal NF-kβ expression, metabolic profile, oxidative stress, inflammatory markers, methylglyoxal (MGO), and glyoxalase-I activity). Forty rats were allotted into four groups (ten rats in each): normal (N), Gln-treated N, Pb intoxication (Pbi), and Gln-treated Pbi. The treated groups took 0.1% Gln in drinking water for 1 month. To motivate lead poisoning, rats gained 50 mg/l lead acetate in drinking water for 1 month. Oxidative stress indices (total glutathione, its reduced and oxidized forms, their ratios, advanced protein oxidation products, malondialdehyde, and ferric ion reducing power) and inflammatory markers (renal nuclear factor-kβ expression, interleukin 1β level, and myeloperoxidase activity) were measured. Furthermore, metabolic profile (fasting blood sugar, insulin, insulin resistance, lipid profile, and atherogenic index) and renal dysfunction parameters were determined. Pb-induced renal histopathological alterations were investigated by a pathologist. In the kidney of Pbi rats, the glomerulus was damaged. Gln prevented kidney damage and reduced kidney dysfunction parameters. In addition, Gln decreased oxidative stress and inflammation in sera and kidney homogenates. In addition, it improved insulin resistance, dyslipidemia, and carbonyl stress (p < 0.001). Gln guarded the kidneys versus lead intoxication by improving insulin resistance and dyslipidemia, elevating antioxidant markers, and diminishing inflammation and carbonyl stress.

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References

  1. Albarakati AJ, Baty RS, Aljoudi AM, Habotta OA, Elmahallawy EK, Kassab RB et al (2020) Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant, anti-inflammatory, antiapoptotic, and Nrf2/HO1 signaling pathways. Mol Biol Rep 47(4):2591–2603

    Article  CAS  PubMed  Google Scholar 

  2. Alhusaini A, Fadda L, Hasan IH, Zakaria E, Alenazi AM, Mahmoud AM (2019) Curcumin ameliorates lead-induced hepatotoxicity by suppressing oxidative stress and inflammation, and modulating Akt/GSK-3 signaling pathway. Biomolecules 9(11):702–718

    Article  Google Scholar 

  3. Fioresi M, Simoes MR, Furieri LB et al (2014) Chronic lead exposure increases blood pressure and myocardial contractility in rats. PLoS One 9(5):96900

    Article  Google Scholar 

  4. Soussi A, Gargouri M, Akrouti A, El Feki A (2018) Antioxidant and nephroprotective effect of Juglans regia vegetable oil against lead-induced nephrotoxicity in rats and its characterization by GCMS. EXCLI J 17:492–504

    PubMed  PubMed Central  Google Scholar 

  5. Apaydın FG, Baş H, Kalender S, Kalender Y (2016) Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats. Environ Toxicol Pharmacol 41:219–224

    Article  PubMed  Google Scholar 

  6. Missoun F, Slimani M, Aoues A (2010) Toxic effect of lead on kidney function in rat Wistar. Afr J Biochem Res 4(2):21–27

    CAS  Google Scholar 

  7. Ritz E, Mann J, Stoeppler M (1988) Lead and the kidney. Adv Nephrol Necker Hosp 17:241–274

    CAS  PubMed  Google Scholar 

  8. Piuri G, Basello K, Rossi G, Soldavini CM, Duiella S, Privitera G et al (2020) Methylglyoxal, glycated albumin, PAF, and TNF-α: possible inflammatory and metabolic biomarkers for management of gestational diabetes. Nutrients 12(2):479

  9. Mahdavifard S, Dehghani R, Jeddi F, Najafzadeh N (2021) 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 24:46–53

    Google Scholar 

  10. Sun B, Karin M (2008) NF-kB signaling, liver disease and hepatoprotective agents. Oncogene 27:6228–6244

    Article  CAS  PubMed  Google Scholar 

  11. Maessen DE, Stehouwer CD, Schalkwijk CG (2015) The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases. Clin Sci 128:839–861

    Article  CAS  Google Scholar 

  12. Rabbani N, Xue M, Weickert MO, Thornalley PJ (2021) Reversal of insulin resistance in overweight and obese subjects by trans-resveratrol and hesperetin combination-link to dysglycemia, blood pressure, dyslipidemia, and low-grade inflammation. Nutrients 11(13):2374

    Article  Google Scholar 

  13. Mey JT, H.J. (2018) Dicarbonyl stress and glyoxalase-1 in skeletal muscle: implications for insulin resistance and type 2 diabetes. Front Cardiovasc Med 5:117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tezuka Y, Nakaya I, Nakayama K, Nakayama M, Yahata M, Soma J (2018) Methylglyoxal as a prognostic factor in patients with chronic kidney disease. Nephrology (Carlton) 24(9):943–950

  15. Pácal L, Chalásová K, Pleskačová A, Řehořová J, Tomandl J, Kaňková K (2018) Deleterious effect of advanced CKD on glyoxalase system activity not limited to diabetes aetiology. Int J Mol Sci 18(19):1517

    Article  Google Scholar 

  16. Kawanami D, Matoba K, Utsunomiya K (2016) Dyslipidemia in diabetic nephropathy. Ren Replace Ther 2(1):1–9

  17. Hasanuzzaman M, Nahar K, Rahman A, Mahmud JA, Alharby HF, Fujita M (2018) Exogenous glutathione attenuates lead-induced oxidative stress in wheat by improving antioxidant defense and physiological mechanisms. J Plant Interact 13(1):203–212

    Article  CAS  Google Scholar 

  18. Mahdavifard S, S.N. (2022) Glutamine is a superior protector against lead-induced hepatotoxicity in rats via antioxidant, anti-inflammatory, and chelating properties. Biol Trace Elem Res 200(11):4726–4732

    Article  CAS  PubMed  Google Scholar 

  19. Newairy AS, Abdou HM (2009) Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats. Food Chem Toxicol 47(4):813–818

    Article  CAS  PubMed  Google Scholar 

  20. Yun S et al (2019) Effects of lead exposure on brain glucose metabolism and insulin signaling pathway in the hippocampus of rats. Toxicol Lett 310:23–30

    Article  CAS  PubMed  Google Scholar 

  21. Flora SJP, V. (2010) Chelation in metal intoxication. Int J Environ Res Public Health 7:2745–2788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mohamed RS, Fouda K, Akl EM (2020) Hepatorenal protective effect of flaxseed protein isolate incorporated in lemon juice against lead toxicity in rats. Toxicol Rep 7:30–35

    Article  PubMed  Google Scholar 

  23. Jalali M (2020) Effect of iron-amino acid chelates on antioxidant capacity and nutritional value of soybean. Plant Prod 43(4):477–486

    Google Scholar 

  24. Kim J, Lee Y, Yang M (2014) Environmental exposure to lead (Pb) and variations in its susceptibility. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 32:159–185

    Article  CAS  PubMed  Google Scholar 

  25. Mima A, Matsubara T, Arai H, Abe H, Nagai K, Kanamori H et al (2006) Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy. Lab Investig 86:927–939

    Article  CAS  PubMed  Google Scholar 

  26. Song YS et al (2016) Comparison of the usefulness of the updated homeostasis model assessment (HOMA2) with the original HOMA1 in the prediction of type 2 diabetes mellitus in Koreans. Diabetes Metab J 40(4):318–325

    Article  PubMed  PubMed Central  Google Scholar 

  27. Taylor EL, Armstrong KR, Perrett D, Hattersley AT, Winyard PG (2015) Optimisation of an advanced oxidation protein products assay: its application to studies of oxidative stress in diabetes mellitus. Oxidative Med Cell Longev 2015:496271

    Article  Google Scholar 

  28. Ahotupa M, Marniemi J, Lehtimäki T, Talvinen K, Raitakari OT, Vasankari T, Viikari J, Luoma J, Ylä-Herttuala S (1998) Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL oxidation. Clin Biochem 31:257–261

    Article  CAS  PubMed  Google Scholar 

  29. Esterbauer H, Gebicki J, Puhl H, Jürgens G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 13:341–390

    Article  CAS  PubMed  Google Scholar 

  30. Benzie IF, Strain J (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239(1):70–76

    Article  CAS  PubMed  Google Scholar 

  31. Begic A et al (2017) The simple isocratic HPLC—UV method for the simultaneous determination of reduced and oxidized glutathione in animal tissue. Acta Chromatogr 29(1):67–84

    Article  CAS  Google Scholar 

  32. Ceron JJ et al (2014) Serum paraoxonase 1 (PON1) measurement: an update. BMC Vet Res 10:74

    Article  PubMed  PubMed Central  Google Scholar 

  33. H, A. (1984) Catalase in vitro. Methods Enzymol 105:121–129

    Article  Google Scholar 

  34. Mazani M, Rezagholizadeh L, Shamsi S, Mahdavifard S, Ojarudi M, Salimnejad R et al (2022) Protection of CCl4-induced hepatic and renal damage by linalool. Drug Chem Toxicol 45(3):963–971

  35. Kavita S, Neerja R, Khushboo G, Saurabh S (2017) Probable benefits of green tea with genetic implications. J Oral Maxillofac Pathol 21:107–114

    Article  Google Scholar 

  36. Rabbani N, Thornalley PJ (2019) Glyoxalase 1 modulation in obesity and diabetes. Antioxid Redox Signal 20(3):354–374

    Article  Google Scholar 

  37. Buraczynska M, Ksiazek K, Wacinski P, Zaluska W (2019) Interleukin-1β gene (IL1B) polymorphism and risk of develo** diabetic nephropathy. Immunol Investig 48(6):1–8

    Article  Google Scholar 

  38. Song N, Thaiss F, Guo L (2019) NFκB and kidney injury. Front Immunol 16(10):815

    Article  Google Scholar 

  39. Gao D, Madi M, Ding C, Fok M, Steele T, Ford C et al (2014) Interleukin-1beta mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. Am J Physiol Endocrinol 307:289–304

    Article  Google Scholar 

  40. Giacco F, Du X, VD D’A, Milne R, Sui G, Geoffrion M, Brownlee M (2014) Knockdown of glyoxalase 1 mimics diabetic nephropathy in nondiabetic mice. Diabetes 63(1):291–299

    Article  CAS  PubMed  Google Scholar 

  41. Ravarotto V, Bertoldi G, Innico G, Gobbi L, Calò LA (2021) The pivotal role of oxidative stress in the pathophysiology of cardiovascular-renal remodeling in kidney disease. Antioxidants 10(7):1041

  42. Gyurászová M et al (2020) Oxidative stress in the pathophysiology of kidney disease: implications for noninvasive monitoring and identification of biomarkers. Oxidative Med Cell Longev 2020:5478708

    Article  Google Scholar 

  43. Welbourne TC (1979) Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney. Can J Biochem 57:233–237

    Article  CAS  PubMed  Google Scholar 

  44. Khatana C, Saini NK, Chakrabarti S, Saini V, Sharma A, Saini RV, Saini AK (2020) Mechanistic Insights into the oxidized low-density lipoprotein-induced atherosclerosis. Oxidative Med Cell Longev 15:2020

    Google Scholar 

  45. da Silva AA et al (2020) Role of hyperinsulinemia and insulin resistance in hypertension: metabolic syndrome revisited. Can J Cardiol 36(5):671–682

    Article  PubMed  Google Scholar 

  46. Whaley-Connell A, Sowers JR (2017) Insulin resistance in kidney disease: is there a distinct role separate from that of diabetes or obesity? Cardiorenal Med 8:41–49

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bjornstad P, Eckel RH (2018) Pathogenesis of lipid disorders in insulin resistance: a brief review. Curr Diab Rep 18(12):416–423

    Article  Google Scholar 

  48. Cieslak MWA, C.M. (2015) Role of pro-inflammatory cytokines of pancreatic islets and prospects of elaboration of new methods for the diabetes treatment. Acta Biochim Pol 62(1):15–21

    Article  CAS  PubMed  Google Scholar 

  49. Vekic J, Vujcic S, Bufan B, Bojanin D, Al-Hashmi K, Al-Rasadi K, Stoian AP, Zeljkovic A, Rizzo M (2023) The role of advanced glycation end products on dyslipidemia. Metabolites 3(13):77

    Article  Google Scholar 

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Acknowledgments

The results explained in this paper were part of the student thesis. The authors are thankful to Ardabil University of Medical Sciences for financial support.

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This study is funded by Ardabil Medical Sciences University.

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(1) Study plan, evaluation, and exegesis of data: Mahdavifard and Najafzadeh. (2) Manuscript writing and revising: Mahdavifard. (3) Ultimate sanction of the version to be submitted and any revised version: Mahdavifard and Najafzadeh.

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Correspondence to Sina Mahdavifard.

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Mahdavifard, S., Nowruz, N. Glutamine Defended the Kidneys Versus Lead Intoxication Via Elevating Endogenous Antioxidants, Reducing Inflammation and Carbonyl Stress, as well as Improving Insulin Resistance and Dyslipidemia. Biol Trace Elem Res 202, 3141–3148 (2024). https://doi.org/10.1007/s12011-023-03887-7

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