Effects of insulin treatment on hepatic CYP1A1 and CYP2E1 activities and lipid peroxidation levels in streptozotocin-induced diabetic rats

Abstract

Introduction

Reactive oxygen species (ROS) and lipid peroxidation (LPO) levels may increase in diabetic state and lead to oxidative stress, which plays a critical role in the progression of diabetes. There are various sources of ROS, including cytochrome P450 monooxygenases (CYP450s), which may be modulated in terms of their activities and expressions under diabetic conditions. This study is aimed to investigate the effects of streptozotocin-induced diabetes and insulin treatment on hepatic cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) activities and LPO levels. Methods: CYP1A1 and CYP2E1 activities were measured with ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, respectively. LPO levels were then corroborated via thiobarbituric acid reactive substances. Results: In diabetic rats, a marked 2.1- and 2.4-fold increase in hepatic CYP1A1 activity and 1.8- and 1.6-fold increase in hepatic CYP2E1 activity were observed compared to controls and insulin-treated diabetic rats, respectively. Hepatic LPO levels in diabetic rats did not significantly change compared to controls. However, in insulin-treated diabetic rats, LPO levels are 0.92- and 0.89-fold remarkably decrease compared to controls and diabetics, respectively. Conclusion: The present study suggests that insulin might have a useful role in the modulation of CYP1A1 and CYP2E1 activities as well as LPO levels in the liver of diabetic rats.

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Fig. 1
Fig. 2

Data svailability

Data are accessible upon request from the authors.

Abbreviations

CYP1A1:

cytochrome P450 1A1

CYP2E1:

cytochrome P450 2E1

CYP450:

cytochrome P450 monooxygenase

EROD:

7-ethoxyresorufinO-deethylase

Fe++ :

Iron(II)

KCI:

potassiumchloride

LPO:

lipid peroxidation

M:

molarity

MDA:

malondialdehyde

MgCI2 :

magnesiumchloride

mins:

minutes

mM:

millimolar

N:

normality

NADP+ :

nicotinamideadenine dinucleotide phosphate

NaOH:

sodiumhydroxide

nm:

nanometer

ºC:

degreesCelsius

pNP:

p-nitrophenol

ROS:

reactive oxygen species

TBARS:

thiobarbituricacid reactive substances

Tris.HCl:

trishydrochloride

U/mL:

unitspermillilitre

v/v:

volume/volume

w/v:

weight/volume

µL:

microliter

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Affiliations

Authors

Contributions

G.K., R.B., and B.C.E. contributed to the concept, design, and analysis of data. E.A.I. has carried out all injections. G.K. and R.B. performed the experimental works. G.K., R.B., and B.C.E. participated in drafting the article.

Corresponding author

Correspondence to Benay Can Eke.

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The authors declare that they have no conflict of interest.

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All procedures used in this study was approved by the Ankara University Local Ethics Committee for Animal Experiments (2010-56-283).

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Kuzgun, G., Başaran, R., Arıoğlu İnan, E. et al. Effects of insulin treatment on hepatic CYP1A1 and CYP2E1 activities and lipid peroxidation levels in streptozotocin-induced diabetic rats. J Diabetes Metab Disord 19, 1157–1164 (2020). https://doi.org/10.1007/s40200-020-00616-y

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Keywords

  • CYP450
  • CYP1A1
  • CYP2E1
  • Diabetes
  • Insulin
  • Streptozotocin