Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol
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 polyph...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/8/723 |
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| author | Tse-En Wang Yu-Hua Lai Kai-Chien Yang Sung-Jan Lin Chih-Lin Chen Pei-Shiue Tsai |
| author_facet | Tse-En Wang Yu-Hua Lai Kai-Chien Yang Sung-Jan Lin Chih-Lin Chen Pei-Shiue Tsai |
| author_sort | Tse-En Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:45:22Z |
| format | Article |
| id | doaj.art-dc137431c50e4cedbffb3f06793e09b0 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T17:45:22Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-dc137431c50e4cedbffb3f06793e09b02023-11-20T09:34:48ZengMDPI AGAntioxidants2076-39212020-08-019872310.3390/antiox9080723Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent HonokiolTse-En Wang0Yu-Hua Lai1Kai-Chien Yang2Sung-Jan Lin3Chih-Lin Chen4Pei-Shiue Tsai5Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, TaiwanDepartment of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, TaiwanResearch Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 10617, TaiwanResearch Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Chemistry, National Taiwan University, Taipei 10617, TaiwanDepartment of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, TaiwanCisplatin, 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.https://www.mdpi.com/2076-3921/9/8/723honokiolcisplatinoxidative stressERTXNDC5testis |
| spellingShingle | Tse-En Wang Yu-Hua Lai Kai-Chien Yang Sung-Jan Lin Chih-Lin Chen Pei-Shiue Tsai Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol Antioxidants honokiol cisplatin oxidative stress ER TXNDC5 testis |
| title | Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol |
| title_full | Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol |
| title_fullStr | Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol |
| title_full_unstemmed | Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol |
| title_short | Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol |
| title_sort | counteracting cisplatin induced testicular damages by natural polyphenol constituent honokiol |
| topic | honokiol cisplatin oxidative stress ER TXNDC5 testis |
| url | https://www.mdpi.com/2076-3921/9/8/723 |
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