Related Experiment Video
Updated: Dec 12, 2025
A High-Throughput Comet Assay Approach for Assessing Cellular DNA Damage
Published on: May 10, 2022
Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol
Tse-En Wang1,2, Yu-Hua Lai1,2, Kai-Chien Yang3,4,5
1Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.
Abstract:
Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFβ1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility.
Insights
Honokiol, delivered via nanosomes, protects against cisplatin-induced testicular toxicity by reducing oxidative stress and apoptosis. This natural compound may allow for reduced cisplatin side effects and restored fertility.
Area of Science:
- Reproductive Toxicology
- Cancer Therapy
- Natural Product Chemistry
Background:
- Cisplatin is a vital chemotherapy agent but causes significant testicular toxicity.
- Reducing cisplatin's damage to normal tissues, particularly the testes, is a critical clinical requirement.
- Honokiol, a natural polyphenol, has demonstrated antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the protective effects of nanosome-encapsulated honokiol against cisplatin-induced testicular injury.
- To elucidate the molecular mechanisms underlying honokiol's protective action.
- To assess the potential of honokiol in mitigating cisplatin's adverse effects on male fertility.
Main Methods:
- In vitro and in vivo studies were conducted using cisplatin and nanosome-encapsulated honokiol.
- Assessed oxidative stress by measuring reactive oxygen species (ROS) and mitochondrial antioxidant enzyme gene expression.
- Evaluated endoplasmic reticulum (ER) stress via the Bip-ATF4-CHOP pathway.
- Quantified DNA damage, apoptosis, and collagen accumulation.
- Analyzed the expression of TGFβ1, αSMA, and TXNDC5.
Main Results:
- Nanosome honokiol suppressed intracellular ROS production and enhanced mitochondrial antioxidant enzyme expression, mitigating oxidative stress.
- Honokiol downregulated the Bip-ATF4-CHOP pathway, alleviating ER stress.
- The compound reduced cisplatin-induced DNA breaks and cellular apoptosis.
- Reduced accumulation of type I collagen was observed, linked to decreased TGFβ1, αSMA, and TXNDC5 expression.
- Preservation of spermatogenic layers and improved sperm cell repopulation were noted.
Conclusions:
- Nanosome-encapsulated honokiol effectively protects against cisplatin-induced testicular toxicity.
- Honokiol mitigates testicular damage by reducing oxidative and ER stress, DNA breaks, and apoptosis.
- This approach shows promise for preserving male fertility during cisplatin chemotherapy.
Related Concept Videos
01:10Drugs that Destabilize Microtubules
02:37DNA Damage can Stall the Cell Cycle