# Pathologic, Laboratory, and Surgical Findings of Topical Statin Gels (Simvastatin, Atorvastatin, and Rosuvastatin) in a Rat Model of Peritoneal Endometriosis

**Authors:** Shahla Chaichian, Roya Derakhshan, Samaneh Rokhgireh, Amirhossein Larijani, Arash Bakhshi, Abolfazl Mehdizadehkashi, Marziyeh Ajdary, Mohammad Abbas Sheikholeslami, Behrang Kazeminezhad, Seyed Ali Ziai, Babak Sabet

PMC · DOI: 10.3390/gels12030201 · 2026-02-28

## TL;DR

This study shows that applying statin gels topically can reduce endometriosis lesions and inflammation in rats, with simvastatin being the most effective.

## Contribution

The study introduces a novel comparative evaluation of topical statin gels for treating peritoneal endometriosis in a rat model.

## Key findings

- All statins significantly reduced endometriotic lesion size compared to controls.
- Simvastatin showed the greatest reduction in adhesion severity and lesion volume.
- Topical statin gels decreased serum IL-6 and IL-1β levels, indicating reduced inflammation.

## Abstract

Endometriosis is a chronic inflammatory disease with frequent recurrence. Statins, due to their anti-inflammatory and antioxidant properties, may help control disease progression, but comparative data on local administration are limited. We evaluated simvastatin-, atorvastatin-, and rosuvastatin-loaded lipophilic gels on lesions, adhesions, and inflammatory markers in a rat model of peritoneal endometriosis. Forty rats were randomized to statin gels (n = 10 each), chitosan gel (vehicle; n = 5), or no treatment (control; n = 5). Two weeks later, lesion size, adhesions, histopathology, and serum Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) were assessed. All statins significantly reduced endometriotic lesion size compared with controls. Lesion volume decreased by approximately 97% with simvastatin, 88% with atorvastatin, and 72% with rosuvastatin, whereas lesion volume increased in the control and vehicle-treated groups. Adhesion severity was markedly reduced, with Hoffman scores decreasing from 7.2 ± 2.25 in controls to 1.9 ± 1.1 with simvastatin, compared with more modest reductions observed with atorvastatin and rosuvastatin. Similarly, Lauder adhesion scores were reduced by approximately 71% with simvastatin, confirming its superior anti-adhesion effect. Serum IL-6 and IL-1β levels were significantly decreased in all statin-treated groups, with no significant differences among statins. Overall, topical statin gel therapy effectively reduced lesion size, adhesions, and inflammation, with simvastatin showing superior anti-adhesion effects.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Chemicals:** Simvastatin (PubChem CID 54454), Atorvastatin (PubChem CID 60823), Rosuvastatin (PubChem CID 446157), Chitosan (PubChem CID 129662530)
- **Diseases:** Endometriosis (MONDO:0005133)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, Il1a (interleukin 1 alpha) [NCBI Gene 24493] {aka IL-1 alpha, IL-1F1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Mmp3 (matrix metallopeptidase 3) [NCBI Gene 17392] {aka EMS-2, MMP-3, SL-1, SLN-1, SLN1, STR-1}
- **Diseases:** Inflammatory (MESH:D007249), ectopic endometrial (MESH:D014591), bowel obstruction (MESH:D012778), Adhesion (MESH:D000267), fibrosis (MESH:D005355), gastrointestinal disturbances (MESH:D005767), infertility (MESH:D007246), pain (MESH:D010146), urinary or renal symptoms (MESH:C563661), dyspareunia (MESH:D004414), dysmenorrhea (MESH:D004412), dyschezia (MESH:D003248), postoperative peritoneal adhesions (MESH:D010538), Endometriosis (MESH:D004715), Endometriotic lesion (MESH:D009059), pelvic pain (MESH:D017699), injury to (MESH:D014947)
- **Chemicals:** Simvastatin (MESH:D019821), hematoxylin (MESH:D006416), H&amp;E (MESH:D006371), PBS (MESH:D007854), formalin (MESH:D005557), Ethylene glycol (MESH:D019855), estradiol (MESH:D004958), xylazine (MESH:D014991), ROS (MESH:D017382), Rosuvastatin (MESH:D000068718), lipid (MESH:D008055), chitosan (MESH:D048271), eosin (MESH:D004801), polyglactin (MESH:D011098), Atorvastatin (MESH:D000069059), oxygen (MESH:D010100), lovastatin (MESH:D008148), acetic acid acetic acid (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025571/full.md

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Source: https://tomesphere.com/paper/PMC13025571