Related Experiment Video
Updated: May 5, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Eicosanoid Derivative, Lipoxin A4, Guards Against Testicular Ferroptosis in Rat Model of Type II Diabetes by
Elshymaa A Abdel-Hakeem1, Manar Fouli Gaber Ibrahim2,3,4, Doaa Mohamed Elroby Ali5,6
1Department of Medical Physiology, Faculty of Medicine, Minia University, Minia 61111, Egypt.
Abstract:
Ferroptosis, a type of iron overload-induced cell death, is involved in diabetes-induced testicular dysfunction. Hence, this study was designed to investigate, for the first time, the impact of lipoxin A4 (LXA4) administration on testicular tissue in diabetic rats and explore its probable role in regulating ferroptosis in comparison with the standard ferroptosis inhibitor (ferrostatin-1, Fer-1). Albino rats of Wistar strain were divided into a control group, a type II diabetes mellitus (DM) group, a DM + Fer-1group, and a DM + LXA4 group. Serum levels of iron, insulin, glucose, total cholesterol, triglycerides, and testosterone were assayed. Testicular tissue markers of oxidative stress, ferroptosis, and inflammation were also assessed by different methods. Our results confirmed diabetes-induced testicular injury and disruption of its function via inducement of ferroptosis, but this was ameliorated with LXA4 and Fer-1 administration. However, Fer-1 showed a greater protective effect compared to LXA4 under the conditions of this study. We concluded that LXA4 partially secured the testicular tissue of diabetic rats against ferroptosis via augmenting the antioxidant Nrf2/SLC7A11/GPX4 pathway. Therefore, LXA4 may have a possible protective effect on the testicular tissue of diabetic patients.
Insights
Lipoxin A4 (LXA4) partially protects diabetic rat testes from ferroptosis, a cell death linked to diabetes. While less effective than ferrostatin-1, LXA4 shows promise for protecting testicular tissue in diabetic patients.
Area of Science:
- Endocrinology
- Cell Biology
- Toxicology
Background:
- Diabetes mellitus (DM) is linked to testicular dysfunction.
- Ferroptosis, an iron-dependent cell death, plays a role in this dysfunction.
- Lipoxin A4 (LXA4) is an endogenous lipid mediator with anti-inflammatory and pro-resolving properties.
Purpose of the Study:
- To investigate the effect of LXA4 on testicular tissue in diabetic rats.
- To explore LXA4's role in regulating ferroptosis compared to ferrostatin-1 (Fer-1).
- To elucidate the underlying molecular mechanisms of LXA4's action.
Main Methods:
- Wistar rats were divided into control, DM, DM + Fer-1, and DM + LXA4 groups.
- Serum analysis included glucose, insulin, lipids, testosterone, and iron levels.
- Testicular tissue was assessed for oxidative stress, ferroptosis, and inflammation markers.
Main Results:
- Diabetes induced testicular injury and dysfunction by promoting ferroptosis.
- Both LXA4 and Fer-1 administration ameliorated diabetes-induced testicular damage.
- Fer-1 demonstrated a more significant protective effect than LXA4 in this study.
- LXA4 partially protected testicular tissue by enhancing the Nrf2/SLC7A11/GPX4 antioxidant pathway.
Conclusions:
- LXA4 offers partial protection against ferroptosis in the testes of diabetic rats.
- The Nrf2/SLC7A11/GPX4 pathway is implicated in LXA4's protective mechanism.
- LXA4 may hold therapeutic potential for protecting testicular tissue in diabetic individuals.