Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model
Background: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to...
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2025-07-01
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| author | Noha A. Alshuwayer Qamraa H. Alqahtani Marwa H. Hussein Raeesa Mohammed Abdulaziz Siyal Iman H. Hasan |
| author_facet | Noha A. Alshuwayer Qamraa H. Alqahtani Marwa H. Hussein Raeesa Mohammed Abdulaziz Siyal Iman H. Hasan |
| author_sort | Noha A. Alshuwayer |
| collection | DOAJ |
| description | Background: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to oxidative stress, apoptosis, and inflammation. Nanocurcumin (NCR) is a nano-formulated edition of curcumin with a higher therapeutic potential. NCR has demonstrated antioxidant and anti-inflammatory properties. Methods: This study is designed to inspect the potential validity of NCR on DOX-induced testicular damage in male rats. We used thirty-two Wistar albino rats (150–200 g) and divided them into four groups. NCR (80 mg/kg/ dissolved in 1% CMC) was given orally by oral gavage for 14 days. A single dose of DOX (15 mg/kg) (i.p.) was injected on the 7th day of the experiment. Results: DOX treatment reduced the sperm viability and motility rate, cellular antioxidants, and gonadal hormones; it led to higher levels of inflammatory mediators, necrosis, and sloughing in seminiferous tubules. Conversely, NCR treatment significantly alleviated these side effects by improving sperm count/motility and reducing sperm abnormalities. The testicular function recovery was likely driven by stimulating the cytoprotective SIRT1/NF-κB pathway, depressing the testicular level of oxidative indicators such as MDA, TNF-α, iNOS, IL-1β, and NO, and increasing levels of antioxidants such as GSH and SOD. In addition, NCR contradicted the apoptotic changes by downregulating the pro-apoptotic signals Bax and caspase-3, while inducing Bcl-2 upregulation. Moreover, NCR increased levels of gonadal hormones, attenuated histological abnormalities, and preserved testicular structure when compared with the DOX group. Conclusions: NCR treatment can effectively ameliorate DOX-induced testicular toxicity. |
| format | Article |
| id | doaj-art-40d3968864774e69bb66bc9be28ff00a |
| institution | Kabale University |
| issn | 2305-6304 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Toxics |
| spelling | doaj-art-40d3968864774e69bb66bc9be28ff00a2025-08-20T03:56:46ZengMDPI AGToxics2305-63042025-07-0113757410.3390/toxics13070574Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat ModelNoha A. Alshuwayer0Qamraa H. Alqahtani1Marwa H. Hussein2Raeesa Mohammed3Abdulaziz Siyal4Iman H. Hasan5Department of Anatomy, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Anatomy, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi ArabiaDepartment of Anatomy, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaBackground: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to oxidative stress, apoptosis, and inflammation. Nanocurcumin (NCR) is a nano-formulated edition of curcumin with a higher therapeutic potential. NCR has demonstrated antioxidant and anti-inflammatory properties. Methods: This study is designed to inspect the potential validity of NCR on DOX-induced testicular damage in male rats. We used thirty-two Wistar albino rats (150–200 g) and divided them into four groups. NCR (80 mg/kg/ dissolved in 1% CMC) was given orally by oral gavage for 14 days. A single dose of DOX (15 mg/kg) (i.p.) was injected on the 7th day of the experiment. Results: DOX treatment reduced the sperm viability and motility rate, cellular antioxidants, and gonadal hormones; it led to higher levels of inflammatory mediators, necrosis, and sloughing in seminiferous tubules. Conversely, NCR treatment significantly alleviated these side effects by improving sperm count/motility and reducing sperm abnormalities. The testicular function recovery was likely driven by stimulating the cytoprotective SIRT1/NF-κB pathway, depressing the testicular level of oxidative indicators such as MDA, TNF-α, iNOS, IL-1β, and NO, and increasing levels of antioxidants such as GSH and SOD. In addition, NCR contradicted the apoptotic changes by downregulating the pro-apoptotic signals Bax and caspase-3, while inducing Bcl-2 upregulation. Moreover, NCR increased levels of gonadal hormones, attenuated histological abnormalities, and preserved testicular structure when compared with the DOX group. Conclusions: NCR treatment can effectively ameliorate DOX-induced testicular toxicity.https://www.mdpi.com/2305-6304/13/7/574nanocurcumindoxorubicinSIRT1apoptosistesticular toxicity |
| spellingShingle | Noha A. Alshuwayer Qamraa H. Alqahtani Marwa H. Hussein Raeesa Mohammed Abdulaziz Siyal Iman H. Hasan Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model Toxics nanocurcumin doxorubicin SIRT1 apoptosis testicular toxicity |
| title | Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model |
| title_full | Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model |
| title_fullStr | Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model |
| title_full_unstemmed | Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model |
| title_short | Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model |
| title_sort | nano curcumin mitigates doxorubicin induced reproductive toxicity via antioxidant anti apoptosis and sirt1 modulating effects in rat model |
| topic | nanocurcumin doxorubicin SIRT1 apoptosis testicular toxicity |
| url | https://www.mdpi.com/2305-6304/13/7/574 |
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