# Resveratrol protects against isoflurane-induced testicular injury: a stereological and molecular study in mice

**Authors:** Zahra Mohammadi, Sanaz Alaee, Majid Kamali-Dolat Abadi, Somayyeh Karami-Mohajeri, Zahra Khodabandeh, Saeed Shokri, Sulagna Dutta, Pallav Sengupta, Hesam Kamyab

PMC · DOI: 10.1016/j.clinsp.2026.100878 · Clinics · 2026-02-19

## TL;DR

Resveratrol may protect mouse testicles from damage caused by isoflurane, an anesthetic, by boosting antioxidants and reducing cell death.

## Contribution

This study demonstrates resveratrol's protective effects against isoflurane-induced testicular toxicity in mice through stereological and molecular analysis.

## Key findings

- Resveratrol mitigated isoflurane-induced reductions in seminiferous tubule volume and length.
- Resveratrol modulated apoptotic genes (Bcl2l1, Bax, Caspase-3) and enhanced antioxidant gene expression (GPX1, Sod1, catalase).
- Higher doses of resveratrol showed greater protective effects against isoflurane toxicity in testicular tissues.

## Abstract

•Resveratrol studied for protection against isoflurane-induced testicular damage.•Sixty C57BL/6 mice were divided into control, isoflurane, and resveratrol groups.•Isoflurane reduced testicular volume, tubular structures, and altered cells.•Resveratrol modulated apoptotic markers and boosted antioxidant gene expression.•Resveratrol shows potential in preventing isoflurane-induced testicular toxicity.

Resveratrol studied for protection against isoflurane-induced testicular damage.

Sixty C57BL/6 mice were divided into control, isoflurane, and resveratrol groups.

Isoflurane reduced testicular volume, tubular structures, and altered cells.

Resveratrol modulated apoptotic markers and boosted antioxidant gene expression.

Resveratrol shows potential in preventing isoflurane-induced testicular toxicity.

This study examines the therapeutic effects of resveratrol, known for its antioxidant and anti-inflammatory properties, in mitigating the harmful effects of isoflurane, an inhalation anesthetic, on testicular tissues in mice.

Sixty adult male C57BL/6 mice were grouped into six categories: control (normal saline), isoflurane only (1.5% for 1-hour/day), low-dose Resveratrol (RSV, 50 mg/kg/day), high-dose RSV (100 mg/kg/day), isoflurane combined with low-dose RSV, and isoflurane combined with high-dose RSV. After 35-days, the mice were euthanized, and their testes were harvested for stereological analysis and the assessment of antioxidant and apoptotic markers.

Exposure to isoflurane resulted in decreased seminiferous tubule volume and length, along with increased interstitial tissue volume of the testis. Co-treatment with resveratrol, especially at higher doses, mitigated these changes. Additionally, resveratrol modulated the expression of the apoptotic genes Bcl2l1, Bax, and Caspase-3, and enhanced the expression of antioxidant genes GPX1, Sod1, and catalase in mice that received isoflurane.

The findings suggest that resveratrol effectively counters isoflurane-induced damage in testicular structures and gene expression, enhancing tubular integrity and antioxidant defense. This indicates a potential therapeutic approach to protect against isoflurane-induced testicular toxicity.

## Linked entities

- **Genes:** BCL2L1 (BCL2 like 1) [NCBI Gene 598], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], Casp3 (caspase 3) [NCBI Gene 12367], GPX1 (glutathione peroxidase 1) [NCBI Gene 2876], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], Cat (Catalase) [NCBI Gene 40048]
- **Chemicals:** resveratrol (PubChem CID 5056), isoflurane (PubChem CID 3763)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Bcl2l1 (BCL2-like 1) [NCBI Gene 12048] {aka Bcl(X)L, Bcl-XL, Bcl2l, BclX, bcl-x, bcl2-L-1}, BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, CAT (catalase) [NCBI Gene 847], CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 14775] {aka CGPx, GPx-1, GSHPx-1, Gpx}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Sod1 (superoxide dismutase 1, soluble) [NCBI Gene 20655] {aka B430204E11Rik, Cu/Zn-SOD, CuZnSOD, Ipo-1, Ipo1, SODC}
- **Diseases:** amnesia (MESH:D000647), spermatogenesis (MESH:C536875), toxicity (MESH:D064420), infertility (MESH:D007246), infections (MESH:D007239), Male infertility (MESH:D007248), reproductive disorders (MESH:D060737), genetic damage (MESH:D030342), testicular damage (MESH:D013733), inflammation (MESH:D007249), atrophy (MESH:D001284)
- **Chemicals:** lipid (MESH:D008055), CO2 (MESH:D002245), polyphenol (MESH:D059808), ROS (MESH:D017382), flavonoids (MESH:D005419), eosin (MESH:D004801), hematoxylin (MESH:D006416), trans-3,4,5-trihydroxystilbene (-), superoxide (MESH:D013481), 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether (MESH:D007530), testosterone (MESH:D013739), free radicals (MESH:D005609), water (MESH:D014867), hydroxyl (MESH:D017665), RSV (MESH:D000077185), paraffin (MESH:D010232), metal (MESH:D008670)
- **Species:** Rheum rhabarbarum (garden rhubarb, species) [taxon 3621], Homo sapiens (human, species) [taxon 9606], Arachis hypogaea (goober, species) [taxon 3818], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12933438/full.md

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Source: https://tomesphere.com/paper/PMC12933438