Related Experiment Video

Updated: Feb 26, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

15.1K

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

Kirtikar Shukla1, Pabitra Bikash Pal1, Himangshu Sonowal1

  • 1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Journal of Diabetes Research
|July 26, 2017
PubMed

Insights

Aldose reductase (AR) inhibitors, like fidarestat, protect cells from high glucose damage by boosting the Nrf2 antioxidant pathway. This enhances the expression of protective enzymes, preparing monocytes against hyperglycemic stress.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Aldose reductase (AR) inhibitors prevent hyperglycemia-induced inflammation.
  • The impact of AR inhibitors on Nrf2-mediated anti-inflammatory responses remains unclear.

Purpose of the Study:

  • To investigate how the AR inhibitor fidarestat protects against high glucose-induced cell viability changes.
  • To determine if fidarestat increases Nrf2 expression and its dependent antioxidant enzymes.

Main Methods:

  • Pretreatment of Thp1 monocytes with fidarestat.
  • Assessing cell viability, Nrf2 expression and DNA-binding activity.
  • Measuring Nrf2-dependent proteins (HO1, NQO1), antioxidant enzymes (SOD, catalase), and AMPK-α1 activation.
  • In vivo studies using STZ-induced diabetic mice.

Main Results:

  • Fidarestat prevented high glucose-induced Thp1 monocyte death.
  • Fidarestat increased Nrf2 expression, DNA-binding activity, and its downstream targets (HO1, NQO1).
  • AR inhibition upregulated Nrf2, HO1, SOD, catalase, and activated AMPK-α1 in cells and diabetic mouse tissues.

Conclusions:

  • Fidarestat pretreatment enhances Nrf2-dependent antioxidant defenses.
  • AR inhibition prepares monocytes against hyperglycemic stress by upregulating antioxidative proteins.

More Related Videos

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

24.5K
Preparation of Naringenin Solution for In Vivo Application08:18

Preparation of Naringenin Solution for In Vivo Application

Published on: August 10, 2021

3.9K

Related Concept Videos

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
669
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
729
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
756
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
4.7K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
7.4K
Phase I Reactions: Reductive Reactions01:27

Phase I Reactions: Reductive Reactions

Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...
662