Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver

T. Thomas, F. Rauscher, R. Sanders, J. Veltman, J. B. Watkins

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.

Original languageEnglish
Pages (from-to)145-149
Number of pages5
JournalToxicological Sciences
Volume53
Issue number1
StatePublished - 2000

Fingerprint

Aldehyde Reductase
Liver
Rats
Antioxidants
Glutathione Reductase
Rabbits
Glutathione Peroxidase
Superoxide Dismutase
Glutathione Disulfide
Catalase
Glutathione
Enzymes
Lipid Peroxidation
Lipids
Oxidative stress
Thiobarbituric Acid Reactive Substances
Enzyme Induction
Diabetes Complications
Biotransformation
Reperfusion Injury

Keywords

  • Aldose reductase inhibitors
  • Catalase
  • Glutathione reductase
  • Lipid peroxidation
  • Reactive oxygen species
  • Superoxide dismutase

ASJC Scopus subject areas

  • Toxicology

Cite this

Thomas, T., Rauscher, F., Sanders, R., Veltman, J., & Watkins, J. B. (2000). Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver. Toxicological Sciences, 53(1), 145-149.

Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver. / Thomas, T.; Rauscher, F.; Sanders, R.; Veltman, J.; Watkins, J. B.

In: Toxicological Sciences, Vol. 53, No. 1, 2000, p. 145-149.

Research output: Contribution to journalArticle

Thomas, T, Rauscher, F, Sanders, R, Veltman, J & Watkins, JB 2000, 'Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver', Toxicological Sciences, vol. 53, no. 1, pp. 145-149.
Thomas T, Rauscher F, Sanders R, Veltman J, Watkins JB. Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver. Toxicological Sciences. 2000;53(1):145-149.
Thomas, T. ; Rauscher, F. ; Sanders, R. ; Veltman, J. ; Watkins, J. B. / Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver. In: Toxicological Sciences. 2000 ; Vol. 53, No. 1. pp. 145-149.
@article{21af90ba2b204edeabbc0cdd95da3459,
title = "Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver",
abstract = "Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.",
keywords = "Aldose reductase inhibitors, Catalase, Glutathione reductase, Lipid peroxidation, Reactive oxygen species, Superoxide dismutase",
author = "T. Thomas and F. Rauscher and R. Sanders and J. Veltman and Watkins, {J. B.}",
year = "2000",
language = "English",
volume = "53",
pages = "145--149",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver

AU - Thomas, T.

AU - Rauscher, F.

AU - Sanders, R.

AU - Veltman, J.

AU - Watkins, J. B.

PY - 2000

Y1 - 2000

N2 - Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.

AB - Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.

KW - Aldose reductase inhibitors

KW - Catalase

KW - Glutathione reductase

KW - Lipid peroxidation

KW - Reactive oxygen species

KW - Superoxide dismutase

UR - http://www.scopus.com/inward/record.url?scp=0033985858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033985858&partnerID=8YFLogxK

M3 - Article

C2 - 10653532

AN - SCOPUS:0033985858

VL - 53

SP - 145

EP - 149

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 1

ER -