Nano-Curcumin Mitigates Doxorubicin-Induced Reproductive Toxicity via Antioxidant, Anti-Apoptosis, and SIRT1-Modulating Effects in Rat Model.

IF 3.9 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Toxics Pub Date : 2025-07-08 DOI:10.3390/toxics13070574

Noha A Alshuwayer, Qamraa H Alqahtani, Marwa H Hussein, Raeesa Mohammed, Abdulaziz Siyal, Iman H Hasan

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引用次数: 0

Abstract

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.

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纳米姜黄素通过抗氧化、抗凋亡和sirt1调节作用减轻阿霉素诱导的大鼠生殖毒性

背景：阿霉素（DOX）是一种有效的抗癌药物，在癌症治疗中被广泛描述。然而，其施用往往受到其副作用的限制，特别是其睾丸毒性，可导致男性患者不育。dox诱导的睾丸损伤是由氧化应激、细胞凋亡和炎症引起的。纳米姜黄素（NCR）是一种具有更高治疗潜力的纳米姜黄素。NCR具有抗氧化和抗炎特性。方法：研究NCR对dox致雄性大鼠睾丸损伤的潜在有效性。选用Wistar白化大鼠32只（150 ~ 200 g），分为4组。NCR （80 mg/kg/溶解于1% CMC中）灌胃14 d。实验第7天注射单剂量DOX (15 mg/kg) （i.p）。结果：DOX治疗降低了精子活力和运动率、细胞抗氧化剂和性腺激素；它导致精管炎症介质、坏死和脱落水平升高。相反，NCR治疗通过提高精子数量/活力和减少精子异常显著减轻了这些副作用。睾丸功能恢复可能是通过刺激细胞保护性SIRT1/NF-κB通路，降低睾丸中MDA、TNF-α、iNOS、IL-1β和NO等氧化指标水平，增加抗氧化剂如GSH和SOD水平驱动的。此外，NCR通过下调促凋亡信号Bax和caspase-3，诱导Bcl-2上调，与凋亡变化相矛盾。此外，与DOX组相比，NCR增加了性腺激素水平，减轻了组织学异常，并保留了睾丸结构。结论：NCR治疗可有效改善dox致睾丸毒性。

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来源期刊

Toxics Chemical Engineering-Chemical Health and Safety

CiteScore

4.50

自引率

10.90%

发文量

681

审稿时长

6 weeks

期刊介绍： Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.