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

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

doi:10.3390/toxics13070574

July 8, 2025ToxicsOpen Access

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

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Why the study?

Doxorubicin administration is limited by adverse effects including testicular toxicity and male infertility, so researchers investigated whether nanocurcumin could mitigate this damage.

Does Nanocurcumin prevent Doxorubicin-induced testicular toxicity in male rats?

Key Points

To evaluate whether nanocurcumin protects against doxorubicin-induced testicular toxicity and investigate the underlying antioxidant, anti-apoptotic, and SIRT1-related signaling pathways.
Randomized thirty-two male Wistar albino rats (150–200 g) across four experimental groups.
Administered nanocurcumin at 80 mg/kg via oral gavage daily for 14 days and delivered a single intraperitoneal dose of doxorubicin at 15 mg/kg on day 7.
Doxorubicin administration impaired sperm count, motility, and viability, depleted cellular antioxidants, and induced necrosis in seminiferous tubules.
Nanocurcumin treatment mitigated oxidative and inflammatory damage by reducing MDA, TNF-α, iNOS, IL-1β, and NO levels while elevating GSH, SOD, and gonadal hormones.
Nanocurcumin stimulated the SIRT1/NF-κB cytoprotective pathway and suppressed apoptosis by downregulating Bax and caspase-3 while upregulating Bcl-2.

Structured PICO

Does Nanocurcumin prevent Doxorubicin-induced testicular toxicity in male rats?

P

Population

32 male Wistar albino rats (150-200 g)

I

Intervention

Nanocurcumin (NCR) 80 mg/kg orally for 14 days + single dose of Doxorubicin (DOX) 15 mg/kg i.p. on day 7

C

Comparator

Doxorubicin (DOX) alone

O

Outcome

Testicular toxicity (sperm viability, motility, cellular antioxidants, gonadal hormones, inflammatory mediators, necrosis)surrogate

Nanocurcumin mitigates doxorubicin-induced testicular toxicity in a rat model by modulating oxidative stress and apoptotic pathways.

Implication

NCR may attenuate DOX testicular toxicity in preclinical models; leaves open clinical utility for fertility preservation during chemotherapy.

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.