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Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats

  • Elvine P. Nguelefack-Mbuyo , Fernande P. Peyembouo , Christian K. Fofié and Télesphore B. Nguelefack
Published/Copyright: April 19, 2021
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 33 Issue 4

Abstract

Objectives

Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities.

Methods

Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated.

Results

Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney.

Conclusions

Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.

Highlights

  1. Subchronic (1,000 µg/kg) and chronic (100 µg/kg) dexamethasone exposure act similarly.

  2. These doses improve glucose tolerance and increase triglyceridemia.

  3. The aforementioned doses increase blood pressure and heart rate.

  4. Subchronic (1,000 µg/kg) and chronic (100 µg/kg) dexamethasone cause renal impairment

  5. Subchronic dexamethasone administration at the dose of 1,000 µg/kg cause oxidative stress

Keywords: dexamethasone; glucose tolerance; hypertension; hypertriglyceridemia; redox status; renal function
Corresponding author: Elvine P. Nguelefack-Mbuyo, Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Dschang, Cameroon, Phone: +237 677 577 539, E-mail:

  1. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  2. Author contributions: EPN-M and TBN designed the study, performed the data analysis and revised the manuscript. FPP drafted the manuscript and collected the data. CKF collected the data.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The study was approved by the departmental review committee in accordance with the standard ethical guidelines for laboratory animal use and care as described in the European Community guidelines EEC Directive.

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Received: 2020-11-01
Accepted: 2021-03-04
Published Online: 2021-04-19

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Minireview
  3. Can pulse wave velocity (PWV) alone express arterial stiffness? A neglected tool for vascular function assessment
  4. Review
  5. Hyponatremia in heart failure: not just 135 to 145
  6. Original Articles
  7. Effects of berberine on cholinesterases and monoamine oxidase activities, and antioxidant status in the brain of streptozotocin (STZ)-induced diabetic rats
  8. Paradoxical sleep deprivation induces oxidative stress in the submandibular glands of Wistar rats
  9. Terminalia arjuna supplementation ameliorates high fat diet-induced oxidative stress in nephrotoxic rats
  10. Decreased expression of annexin A2 and loss of its association with vascular endothelial growth factor leads to the deficient trophoblastic invasion in preeclampsia
  11. Algogen-induced vasosensory reflexes modulate short-term heart rate variability parameters in experimental rat models
  12. Assessment of sleep quality and its predictors among newly diagnosed psychiatric patients
  13. Ovalbumin/lipopolysaccharide induced vasculitis in rats: a new predictive model
  14. Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats
  15. Effects of sleeve gastrectomy on neutrophil–lymphocyte ratio
  16. Effect of luteolin on the gene level expression of apoptosis-associated speck-like protein containing a caspase recruitment domain of NLRP3 inflammasome and NF-κB in rats subjected to experimental pancreatitis – influence of HSP70
  17. Effects of Onosma dichroanthum Boiss. root extract on AGS human gastric cancer cell-line
  18. Feasibility, face, and content validity of quantitative computed tomography in interstitial lung disease related to connective tissue diseases
  19. In vitro anticoagulant activity of selected medicinal plants: potential interactions with warfarin and development of new anticoagulants
  20. Normal reference value of orthodromic and antidromic sensory nerve conduction velocity of median nerve with intact palmaris longus tendon in apparently healthy individuals
  21. Short Communication
  22. Chemokine receptor antagonists with α1-adrenergic receptor blocker activity
https://doi.org/10.1515/jbcpp-2020-0365
Keywords for this article
dexamethasone; glucose tolerance; hypertension; hypertriglyceridemia; redox status; renal function

Articles in the same Issue

  1. Frontmatter
  2. Minireview
  3. Can pulse wave velocity (PWV) alone express arterial stiffness? A neglected tool for vascular function assessment
  4. Review
  5. Hyponatremia in heart failure: not just 135 to 145
  6. Original Articles
  7. Effects of berberine on cholinesterases and monoamine oxidase activities, and antioxidant status in the brain of streptozotocin (STZ)-induced diabetic rats
  8. Paradoxical sleep deprivation induces oxidative stress in the submandibular glands of Wistar rats
  9. Terminalia arjuna supplementation ameliorates high fat diet-induced oxidative stress in nephrotoxic rats
  10. Decreased expression of annexin A2 and loss of its association with vascular endothelial growth factor leads to the deficient trophoblastic invasion in preeclampsia
  11. Algogen-induced vasosensory reflexes modulate short-term heart rate variability parameters in experimental rat models
  12. Assessment of sleep quality and its predictors among newly diagnosed psychiatric patients
  13. Ovalbumin/lipopolysaccharide induced vasculitis in rats: a new predictive model
  14. Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats
  15. Effects of sleeve gastrectomy on neutrophil–lymphocyte ratio
  16. Effect of luteolin on the gene level expression of apoptosis-associated speck-like protein containing a caspase recruitment domain of NLRP3 inflammasome and NF-κB in rats subjected to experimental pancreatitis – influence of HSP70
  17. Effects of Onosma dichroanthum Boiss. root extract on AGS human gastric cancer cell-line
  18. Feasibility, face, and content validity of quantitative computed tomography in interstitial lung disease related to connective tissue diseases
  19. In vitro anticoagulant activity of selected medicinal plants: potential interactions with warfarin and development of new anticoagulants
  20. Normal reference value of orthodromic and antidromic sensory nerve conduction velocity of median nerve with intact palmaris longus tendon in apparently healthy individuals
  21. Short Communication
  22. Chemokine receptor antagonists with α1-adrenergic receptor blocker activity
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