Skip to main content
SpringerLink
Log in

Effects of diabetes on oxidative and nitrosative stress in kidney mitochondria from aged rats

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Diabetes mellitus (DM) is characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. Diabetic nephropathy (DN) develops in diabetic patients and is characterized by a progressive deterioration of renal function. The mitochondrial electron transport chain (ETC) produces most of the reactive oxygen species (ROS) that are involved in diabetic nephropathy. Due to the high incidence of DM in the elderly, the aim of this study was to evaluate oxidative and nitrosative stress in kidney mitochondria from aged rats. We evaluated lipid peroxidation (LPO), nitric oxide (NO•) production, S-nitrosylation profiles, glutathione levels, and glutathione reductase and aconitase activities under streptozotocin (STZ)-induced experimental diabetes in kidney mitochondria from aged rats. The results showed an increase in LPO, NO• production, and S-nitrosylated proteins in rats with STZ-induced diabetes. A decrease in glutathione (GSH) levels and glutathione reductase (GR) and aconitase activities in the rats that received the STZ-induced diabetes treatment was also observed, when compared with the age-related controls. The data suggest that oxidative and nitrosative stresses promote mitochondrial oxidative dysfunction in the more advanced age rat kidney in STZ-induced diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Akerboom TP, Sies H (1981) Assay of glutathione, glutathione disuylfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 77:373–382

    Article  CAS  Google Scholar 

  • Baylis C (2012) Nitric oxide synthase derangements and hypertension in kidney disease. Curr Opin Nephrol Hypertens 21(1):1–6

    Article  CAS  Google Scholar 

  • Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9(5):836–844

    Article  CAS  Google Scholar 

  • Benzi G, Moretti A (1995) Age- and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutathione system. Free Radic Biol Med 19(1):77–101

    Article  CAS  Google Scholar 

  • Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH (2002) Ageing and diabetes: implications for brain function. Eur J Pharmacol 441(1–2):1–14

    Article  CAS  Google Scholar 

  • Buegue JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–320

    Article  Google Scholar 

  • Burcelin R, Kande J, Ricquier D, Girard J (1993) Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia. Biochem J 291(Pt 1):109–113

    CAS  Google Scholar 

  • Cai J, Nelson KC, Wu M (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res 19(2):205–221

    Article  CAS  Google Scholar 

  • Carlberg I, Mannervick B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    Article  CAS  Google Scholar 

  • Duan J, Kasper DL (2011) Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology 21(4):401–409

    Article  CAS  Google Scholar 

  • Ghafourifar P, Richter C (1997) Nitric oxide synthase activity in mitochondria. FEBS Lett 418(3):291–296

    Article  CAS  Google Scholar 

  • Ghafourifar P, Saavedra-Molina A (2006) Functions of mitochondrial nitric oxide synthase. In Lamas S, Cadenas E. eds. Nitric oxide, cell signaling, and gene expression (pp 77–98). Taylor & Francis

  • Gomez-Cabrera MC, Sanchis-Gomar F, Garcia-Valles R, Pareja-Galeano H, Gambini J, Borras C, Viña J (2012) Mitochondria as sources and targets of damage in cellular aging. Clin Chem Lab Med 50(8):1287–1295

    Article  CAS  Google Scholar 

  • Green LC, Wagner DA, Glowoski J, Skipper PI, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, and [15 N] nitrate in biological fluids. Anal Biochem 126(1):131–138

    Article  CAS  Google Scholar 

  • Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53(Supl 1):110–118

    Article  Google Scholar 

  • Henson CP, Cleland WW (1967) Purification and kinetic studies of beef liver cytoplasmic aconitase. J Biol Chem 242(17):3833–3838

    CAS  Google Scholar 

  • Hou J, Chong ZZ, Shang YC, Maiese K (2010) Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res 7(2):95–112

    Article  CAS  Google Scholar 

  • Kim MK, Ko SH, Baek KH, Ahn YB, Yoon KH, Kang MI, Lee KW, Song KH (2009) Long-term effects of rosiglitazone on the progressive decline in renal function in patients with type 2 diabetes. Korean J Intern Med 24(3):227–232

    Article  CAS  Google Scholar 

  • Kobayashi H, Tokudome G, Hara Y, Sugano N, Endo S, Suetsugu Y, Kuriyama S, Hosoya T (2009) Insulin resistance is a risk factor for the progression of chronic kidney disease. Clin Nephrol 71(6):643–651

    Article  CAS  Google Scholar 

  • Ku HH, Brunk UT, Sohal RS (1993) Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Radic Biol Med 15(6):621–627

    Article  CAS  Google Scholar 

  • Lash LH (2006) Mitochondrial glutathione transport: physiological, pathological and toxicological implications. Chem Biol Interact 163(1–2):54–67

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  Google Scholar 

  • Maddineni S, Nichenametla S, Sinha R, Wilson RP, Richie JP Jr (2013) Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat. Exp Biol Med (Maywood) 238(4):392–399

    Article  Google Scholar 

  • Manna P, Sinha M, Sil PC (2009) Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades. Chem Biol Interact 181(3):297–308

    Article  CAS  Google Scholar 

  • Martens CR, Edwards DG (2011) Peripheral vascular dysfunction in chronic kidney disease. Cardiol Res Pract 2011:267257

    Google Scholar 

  • Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D, Batinic-Haberle I (2012) Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta 1822(5):794–814

    Article  CAS  Google Scholar 

  • Muyderman H, Nilsson M, Sims NR (2004) Highly selective and prolonged depletion of mitochondrial glutathione in astrocytes markedly increases sensitivity to peroxynitrite. J Neurosci 24(37):8019–8028

    Article  CAS  Google Scholar 

  • Nakano M, Oenzil F, Mizuno T, Gotoh S (1995) Aged related changes in the lipofuscin accumulation of brain and heart. Int J Exp Clin Gerontol 41(2):69–79

    CAS  Google Scholar 

  • Noriega-Cisneros R, Cortés-Rojo C, Manzo-Avalos S, Clemente-Guerrero M, Calderón-Cortés E, Salgado-Garciglia R, Montoya-Pérez R, Boldogh I, Saavedra-Molina A (2013) Mitochondrial response to oxidative and nitrosative stress in early stages of diabetes. Mitochondrion 13(6):835–840

    Article  CAS  Google Scholar 

  • Ognjanovic BI, Djorjovic NZ, Matic MM, Obradovic JM, Mladenovic JM, Stajn AS, Saicic ZS (2012) Lipid peroxidative damage on cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium. Int J Mol Sci 13(2):1790–1803

    Article  Google Scholar 

  • Okumura M, Masada M, Yoshida Y, Hosoi M, Konishi Y, Morikawa T, Miura K (2006) Decrease in tetrahydrobiopterin as a possible cause of nephropathy in type II diabetic rats. Kidney Int 70(3):471–476

    CAS  Google Scholar 

  • Ortiz-Avila O, Sámano-García CA, Calderón-Cortés E, Pérez-Hernández IH, Mejía-Zepeda R, Rodríguez-Orozco AR, Saavedra-Molina A, Cortés-Rojo C (2013) Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria. J Bioenerg Bioembr 45(3):271–287

    Article  CAS  Google Scholar 

  • Öztürk G, Akbulut KG, Güney S, Acuña-Castroviejo D (2012) Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: modulation by melatonin. Exp Gerontol 47(9):706–711

    Article  Google Scholar 

  • Pollock JS, Pollock DM (2011) Endothelin, nitric oxide, and reactive oxygen species in diabetic kidney disease. Contrib Nephrol 172:149–159

    Article  CAS  Google Scholar 

  • Prabhakar S, Starnes J, Shi S, Lonis B, Tran R (2007) Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J Am Soc Nephrol 18(11):2945–2952

    Article  CAS  Google Scholar 

  • Radi R, Cassina A, Hodara R (2002) Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem 383(3–4):401–409

    CAS  Google Scholar 

  • Saavedra-Molina A, Devlin TM (1997) Effect of extra-and intra-mitochondrial calcium on citrulline synthesis in rat liver. Amino Acids 12:293–298

    Article  CAS  Google Scholar 

  • Sanz A, Rhoda SKA (2008) The mitochondrial free radical theory of aging: a critical review. Curr Aging Sci 1(1):10–21

    Article  CAS  Google Scholar 

  • Schena FP, Gesualdo L (2005) Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 16(Suppl 1):S30–S33

    Article  CAS  Google Scholar 

  • Shi I, Sawada M (1994) Alterations in free radicals activity in aging drosophila. Exp Gerontol 29(5):574–584

    Article  Google Scholar 

  • Sohal RS (1993) The free radical hypothesis of aging: an appraisal of the current status. Aging (Milano) 5(1):3–17

    CAS  Google Scholar 

  • Sohal RS, Arnold LA, Sohal BH (1990) Aged-related changes in antioxidants enzymes and pro-oxidant generation in tissues of the rat with special reference to parameters in two insect species. Free Radic Biol Med 9(6):495–500

    Article  CAS  Google Scholar 

  • Tórtora V, Quijano C, Freeman B, Radi R, Castro L (2007) Mitochondrial aconitase reaction with nitric oxide, S-nitrosoglutathione, and peroxynitrite: mechanisms and relative contributions to aconitase inactivation. Free Radic Biol Med 42(7):1075–1088

    Article  Google Scholar 

  • Turki A, Hayot M, Carnac G, Pillard F, Passerieux E, Bomart S, Raynaud de Mauverger E, Hugon G, Pincemail J, Pietri S, Lambert K, Belayew A, Vassetzky Y, Juntas Morales R, Mercier J, Laoudj- Chenivesse D (2012) Functional muscle impairment in fascioscapulohumeral muscular distrophy is correlated with oxidative stress and mitochondrial dysfunction. Free Radic Biol Med 53(5):1068–1079

    Article  CAS  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84

    Article  CAS  Google Scholar 

  • Van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, Palacios-Callender M, Erusalimsky JD, Quaschning T, Malinski T, Gygi D, Ullrich V, Lüscher TF (2000) Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192(12):1731–1743

    Article  Google Scholar 

  • Wang S, Sun QQ, Xiang B, Li XJ (2013) Pancreatic islet cell autophagy during aging in rats. Clin Invest Med 36(2):E72–E80

    CAS  Google Scholar 

  • Warner HR (1994) Superoxide dismutase, aging and degenerative diseases. Free Radic Biol Med 7(3):249–258

    Article  Google Scholar 

  • WHO, World Health Organization (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of WHO Consultation, Geneva, Switzerland

  • Yarian CS, Sohal RS (2005) In the aging housefly aconitase is the only citric acid cycle enzyme to decline significantly. J Bioenerg Biomembr 37(2):91–96

    Article  CAS  Google Scholar 

  • Yarian CS, Rebrin I, Sohal RS (2005) Aconitase and ATP synthase are targets of malondialdehyde modification and undergo an age-related decrease in activity in mouse heart mitochondria. Biochem Biophys Res Commun 330(1):151–156

    Article  CAS  Google Scholar 

  • Yarian CS, Toroser D, Sohal RS (2006) Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice. Mech Ageing Dev 127(1):79–84

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by CIC-UMSNH grants (2.10 to RSG; 2.16 to ASM; 2.37 to SMA); CONACYT (130638 to CCR; 169093 to ASM). RVPG, RNC and EEG received CONACYT fellowships.

Author information

Authors and Affiliations

  1. Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3. C.U., Morelia, Mich, 58030, Mexico

    Rocío V. Pérez-Gallardo, Ruth Noriega-Cisneros, Edgar Esquivel-Gutiérrez, Christian Cortés-Rojo, Salvador Manzo-Avalos, Jesús Campos-García, Rafael Salgado-Garciglia, Rocío Montoya-Pérez & Alfredo Saavedra-Molina

  2. Facultad de Enfermería, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich, Mexico

    Elizabeth Calderón-Cortés

  3. University of Texas Medical Branch at Galveston Texas, Galveston, TX, USA

    Istvan Boldogh

Authors
  1. Rocío V. Pérez-Gallardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruth Noriega-Cisneros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edgar Esquivel-Gutiérrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth Calderón-Cortés
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Cortés-Rojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Salvador Manzo-Avalos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jesús Campos-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rafael Salgado-Garciglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rocío Montoya-Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Istvan Boldogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alfredo Saavedra-Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Saavedra-Molina.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Gallardo, R.V., Noriega-Cisneros, R., Esquivel-Gutiérrez, E. et al. Effects of diabetes on oxidative and nitrosative stress in kidney mitochondria from aged rats. J Bioenerg Biomembr 46, 511–518 (2014). https://doi.org/10.1007/s10863-014-9594-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-014-9594-4

Keywords

Search

Navigation