Related Experiment Video
Updated: Mar 16, 2026
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Potential gonadal-beneficial effect of sitagliptin against paclitaxel-induced testicular dysfunction via mediating
Kareman M El-Beheiry1, Nagla A El-Shitany2, Magda El-Sayed El-Sayad2
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt. kariman@pharm.tanta.edu.eg.
Abstract:
Paclitaxel (PTX) is broadly prescribed to treat various malignancies. However, it induces negative impacts on many organs, including testes. This study explored the beneficial role of sitagliptin (SIT) in PTX-provoked testicular damage and the underlying mechanisms. Rats were allocated into four groups: (I) control, (II) PTX, (III) PTX + SIT5, and (IV) PTX + SIT10. Histopathological and ultrastructural analyses were conducted along with sperm analysis. Immunohistochemical examinations of NOD-like receptor protein 3 (NLRP3), cleaved caspase-3, caspase-3, cytochrome c (Cyt.c), and interleukin-1 beta (IL-1β) were assessed. Serum testosterone and testicular 17β-hydroxy steroid dehydrogenase (17β-HSD), sestrin2, phosphorylated protein kinase R-like ER kinase (pPERK), and C/EBP homologous protein (CHOP) were determined. SIT induced a remarkable increase in sperm count, motility, and viability, with a pronounced decline in sperm abnormality compared to PTX group. SIT increased testosterone and 17β HSD levels. SIT elevates sestrin2, reduced glutathione (GSH), and catalase, and reduces malondialdehyde (MDA), reflecting its antioxidant action. SIT mitigates ER stress via diminishing pPERK and CHOP. SIT reduces NLRP3 and IL-1β levels, clarifying its anti-inflammatory action. SIT decreases cleaved caspase-3, caspase-3, and Cyt.c levels, verifying its anti-apoptotic features. Overall, SIT ameliorated PTX-provoked testicular dysfunction via mediating PERK/CHOP/NLRP3/Sestrin2 signaling pathway.
Insights
Sitagliptin (SIT) protects against paclitaxel (PTX)-induced testicular damage by improving sperm quality and reducing inflammation and apoptosis. It works by modulating the PERK/CHOP/NLRP3/Sestrin2 signaling pathway.
Area of Science:
- Pharmacology
- Toxicology
- Reproductive Biology
Background:
- Paclitaxel (PTX) is a widely used chemotherapy agent with known testicular toxicity.
- Understanding protective mechanisms against PTX-induced testicular damage is crucial for patient care.
Purpose of the Study:
- To investigate the protective effects of sitagliptin (SIT) against PTX-induced testicular injury in rats.
- To elucidate the underlying molecular mechanisms, including endoplasmic reticulum (ER) stress, inflammation, and apoptosis.
Main Methods:
- Rats were treated with PTX alone or in combination with different doses of SIT.
- Evaluations included histopathological analysis, sperm analysis, and assessment of key molecular markers (e.g., NLRP3, caspase-3, Cyt.c, testosterone, pPERK, CHOP, sestrin2).
Main Results:
- SIT significantly improved sperm count, motility, and viability while reducing abnormalities.
- SIT demonstrated antioxidant effects by increasing glutathione and catalase and decreasing malondialdehyde.
- SIT mitigated ER stress, inflammation (NLRP3, IL-1β), and apoptosis (caspase-3, Cyt.c).
Conclusions:
- Sitagliptin ameliorates paclitaxel-induced testicular dysfunction.
- The protective effects are mediated through the modulation of the PERK/CHOP/NLRP3/Sestrin2 signaling pathway, highlighting its potential therapeutic role.
Related Concept Videos
01:23Dipeptidyl Peptidase 4 Inhibitors
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...