Skip to main content
SpringerLink
Log in

Role of DL α-lipoic acid in gentamicin induced nephrotoxicity

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The effect of DL α-lipoic acid on the nephrotoxic potential of gentamicin was examined. Intraperitoneal injection of gentamicin (100 mg/kg/day) to rats resulted in decreased activity of the glycolytic enzymes-hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase. The two gluconeogenic enzymes—glucose-6-phosphatase and fructose-1, 6-diphosphatase, the transmembrane enzymes namely the Na+, K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and the brushborder enzyme alkaline phosphatase, also showed decreased activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush border membrane damage. Decreased activity of the TCA cycle enzymes isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), suggests a loss in mitochondrial integrity. These biochemical disturbances were effectively counteracted by lipoic acid administration. Lipoic acid administration by gastric intubation at two different concentrations (10 mg and 25 mg/kg/day) brought about an increase in the activity of the glycolytic enzymes, ATPases and the TCA cycle enzymes. The gluconeogenic enzymes however showed a further decrease in their activities at both the concentrations of lipoic acid administered. These observations shed light on the nephroprotective action of lipoic acid against experimental aminoglycoside toxicity and the protection afforded at 25 mg/kg/day of lipoic acid was noted to be higher than that at 10 mg level.

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

Similar content being viewed by others

References

  1. Walter AM, Heilmeier L: In: H. Otten, M. Plempel and W. Siegenthaler (eds). Antibiotika-Fibel, Thieme, Stuttgart, 1975, p 362

    Google Scholar 

  2. GinnShelburne J, Trump B: Disorders of cell Volume regulation. Am J Pathol 53: 1041–1071, 1968

    Google Scholar 

  3. Horio M, Fukuhara Y, Orita Y, Akanishi T, Nakahara H, Moriyama T, Kumada T: Gentamicin inhibits Na+ dependent glucose transport in rabbit kidney brush border membrane vesicles. Biochim Biophys Acta 858: 153–160, 1986

    Google Scholar 

  4. Biber J, Hauser H: The role of SH-group in the concentrative transport of D-glucose into brush border membrane vesicles. FEBS Lett 108(2): 451–456, 1979

    Google Scholar 

  5. Masayuki T, Yukihiko A, Asaichi I, Seishi T: Inhibition of alkaline phosphatase activity and D-glucose uptake in rat renal brush border membrane vesicles by aminoglycosides. Biochim Biophys Acta 903: 31–36, 1987

    Google Scholar 

  6. Belly GD, Williams RJ: Effect of lipoic acid on the growth rate of young rats. Arch Biochem Biophys 55: 587–588, 1955

    Google Scholar 

  7. Jayanthi S, Jayanthi G, Varalakshmi P: Effect of DL α-lipoic acid on some carbohydrate metabolising enzymes in stone forming rats. Biochem Int 25(1): 123–136, 1991

    Google Scholar 

  8. Haugaard N, Haugaard ES: Stimulation of glucose utilisation by thiotic acid in rat diaphragm incubatedin vitro. Biochim Biophys Acta 222: 583–586, 1970

    Google Scholar 

  9. Gandhi VM, Wagh SS, Nataraj CV, Menon KKG: Lipoic acid and diabetes II. Mode of action of lipoic acid. J Bio Sci 9: 117–127, 1985

    Google Scholar 

  10. Bashan N, Burdett E, Guma A, Klip A: Effect of Thioctic acid on glucose transport. In: F.A. Gries and K. Wessel (eds). The role of antioxidants in Diabetes mellitus. Oxygen radicals and antioxidants in Diabetes. Frankfurt am Main: pmi verl-Gruppe, Germany, 1993, pp 221–229

    Google Scholar 

  11. Branstrup N, Kirk JE, Bruni C: The hexokinase and phosphoglucoisomerase activities of aortic and pulmonary artery tissue in individuals of various ages. J Gerentol 238: 3280, 1963

    Google Scholar 

  12. Horrocks JE, Ward J, King J: A routine method for the determination of phosphoglucoisomerase activity in body fluid. J Clin Pathol 16: 248, 1963

    Google Scholar 

  13. King J: The trasferases—alanine and aspartate transaminases. In: D. Van (ed). Practical Clinical Enzymology, Nostrand Company Ltd, London, 1965, pp 121–138

    Google Scholar 

  14. King J: The dehydrogenases or Oxido reductases—lactate dehydrogenase. In: D. Van (ed). Practical Clinical Enzymology, Nostrand Company Ltd, London, 1965, pp 83–93

    Google Scholar 

  15. King J: The phosphohydrolases—acid and alkaline phosphatase. In: D. Van (ed). Practical Clinical Enzymology, Nostrand Company Ltd, London, 1965, pp 191–208

    Google Scholar 

  16. Gansede JM, Gancedo C: Fructose-1,6-diphosphatase, phosphofructokinase and glucose-6-phosphate dehydrogenase fermenting and non fermenting yeasts. Arch Microbiol 76: 132, 1971

    Google Scholar 

  17. Bonting SL: Sodium—potasium activated adenosine triphosphatase and cation transport. In: E.E. Bittar (ed). Membrane ion transport. Wiley Interscience, England, 1970, pp 257–363

    Google Scholar 

  18. Ohnishi T, Suzuki T, Ozawas K: A comparative study of plasma membrane magnesium ion ATPase activities in normal, regenerating and malignant cells. Biochim Biophys Acta 684: 67–74, 1982

    Google Scholar 

  19. Hjerten S, Pan H: Purification and characterisation of two forms of a low affinity calcium ion ATPase from erythrocyte membrane. Biochim Biophys Acta 755: 457–456, 1983

    Google Scholar 

  20. Slater EC, Bonner WD: Succinate dehydrogenase. Biochem J 52: 185–196, 1952

    Google Scholar 

  21. Mehler AH, Komberg A, Crisolen S, Ochon S: J Biol Chem 174: 961–977, 1948

    Google Scholar 

  22. Sasaki T, Matsuy S, Sanae A: Effect of acetic acid concentration on the colour reaction in the O.toluidine—boric acid method for blood glucose determination. Rinsho Kagaku 1: 346, 1972

    Google Scholar 

  23. Fiske CH, Subbarow Y: The colorimetric determination of phosphorus. J Biol Chem 66: 375, 1925

    Google Scholar 

  24. Lowry OH, Rosenbrough NJ, Farr AI, Randall RJ: Protein measurement with the Folin-phenol reagent. J Biol Chem 193: 265, 1951

    Google Scholar 

  25. Kishore BK, Kallay Z, Lambricht P, Laurent G, Tulkens PM: Mechanism of protection afforded by poly aspartic acid against gentamicin induced phospholipidosis. 1. Polyaspartic acid binds gentamicin and displaces it from negatively charged phospholipid bilayersin vitro. J Pharmacol Exp Ther 255: 867–874, 1990

    Google Scholar 

  26. Smith CR, Lipsky JJ, Laskin OL, Hellmann DB, Mellits ED, Longstreth J, Lietman PS: Double-bind comparison of the nephrotoxicity and auditory ototoxicity of gentamicin and tobramycin. N Engl J Med 302: 1106–1109, 1980

    Google Scholar 

  27. Takahashi M, Aramaki Y, Inaba A, Tsuchiya S: Inhibition of alkaline phosphatase activity and D-glucose uptake in rat renal brush border membrane vesicles by aminoglycosides. Biochim Biophys Acta 903: 31–36, 1987

    Google Scholar 

  28. Singh HPP, Bouman RH: Effect of DL α-lipoic acid on the citrate concentration and phosphofructokinase activity of perfused hearts from normal and diabetic rats. Biochem Biophys Res Commun 41: 555–561, 1970

    Google Scholar 

  29. Bluementhal SA: Inhibition of gluconeogenesis in rat liver by lipoic acid—Evidence for more than one site of action. Biochem J 219: 773–780, 1984

    Google Scholar 

  30. Williams PD, Trimble ME, Crespo L, Holohan PD, Freedmon JC, Ross CR: Inhibition of renal Na+, K+-adenosine triphosphatase by gentamicin. J Pharmacol Exp Ther 231: 248–253, 1984

    Google Scholar 

  31. Kacew S: Inability of nitrendipine to protect against gentamicin nephrotoxicity in the rat. Biomed Environ Sci 2: 160–166, 1989

    Google Scholar 

  32. Weinberg MJ, Humes DH: Mechanisms of gentamicin induced dysfunction of renal cortical mitochondria. I. Effects on mitochondrial respiration. Arch Biochem Biophys 205: 222–231, 1980

    Google Scholar 

  33. Weinberg MJ, Harding GP, Humes DH: Mechanisms of gentamicin induced dysfunction of renal cortical mitochondria. II. Effects on mitochondrial monovalent cation transport. Arch Biochem Biophys 205: 232–239, 1980

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, Post Graduate Institute of Basic Medical Sciences, (Taramani Campus,), 600 113, Madras, India

    P. Sandhya, S. Mohandass & P. Varalakshmi

Authors
  1. P. Sandhya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Mohandass
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Varalakshmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sandhya, P., Mohandass, S. & Varalakshmi, P. Role of DL α-lipoic acid in gentamicin induced nephrotoxicity. Mol Cell Biochem 145, 11–17 (1995). https://doi.org/10.1007/BF00925707

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00925707

Key Words

Search

Navigation