Embryotoxic and Oxidative Impact of Dapagliflozin: A Dose-Dependent Study Using a Chick Embryo Model

Area of Science:

• Pharmacology
• Developmental Toxicology
• Embryology

Background:

• Dapagliflozin is a widely prescribed SGLT2 inhibitor for type 2 diabetes.
• Its teratogenic potential during early development is not well understood.
• Understanding drug safety in pregnancy is crucial.

Purpose of the Study:

• To investigate the dose-dependent teratogenic effects of dapagliflozin.
• To assess the safety of dapagliflozin during early developmental stages using a chick embryo model.

Main Methods:

• Fertilized chick eggs were treated with dapagliflozin (1.0-2.5 mg/mL) on embryonic Day 3.
• Morphometric analysis, histological examination, and oxidative stress assays (DPPH, SOD, CAT) were performed.
• Developmental endpoints including body weight, survival, organ histology, and reactive oxygen species (ROS) levels were evaluated.

Main Results:

• Dapagliflozin caused dose-dependent reductions in body weight (up to 47%) and increased mortality (40% at 2.5 mg/mL).
• Histological findings included hepatic steatosis, pulmonary emphysema, cardiac inflammation, neural apoptosis, and vascular abnormalities.
• Elevated ROS levels and significant radical scavenging activity indicated oxidative stress as a key mediator.

Conclusions:

• Dapagliflozin exhibits dose-dependent teratogenicity in a nonmammalian vertebrate model.
• Findings suggest potential risks associated with dapagliflozin use during pregnancy.
• Further mammalian studies are warranted to evaluate human health implications.