Amlodipine mitigates Cisplatin- and acetaminophen-induced nephrotoxicity associated with alterations in renal gamma-glutamyl transpeptidase and oxidative stress.

Protection by maslinic acid against cisplatin-induced ototoxicity: rescue of ferroptosis by targeting the SLC7A11-GSH-GPX4 pathway.

The angiotensin II receptor blocker candesartan mitigates cisplatin-induced myocardial injury via suppression of TLR-4/NF-κB/IRF-3/AP-1 signaling and restoration of antioxidant defenses.

Ellagic acid (EA) is a natural polyphenol noted for its antiproliferative and pro-apoptotic effects. This study investigates the impact of EA, alone or combined with cisplatin (CIS), on the expression of angiogenesis, apoptosis, metastasis, and chemoresistance-related genes and proteins in cisplatin-sensitive and -resistant MDA-MB-231 breast cancer cells. Cell viability was evaluated by cytotoxicity assay, while gene and protein expression levels were analyzed via qPCR and immunocytochemistry. Molecular docking was used to assess EA's binding affinity to target proteins. The IC₅₀ values of EA and CIS were 29 µM and 38.2 µM in cisplatin-sensitive MDA-MB-231 cells, and 49.5 µM and 80.2 µM in cisplatin-resistant cells, respectively. In both cell types, EA significantly decreased the expression of the ABCB1 and VEGF genes, especially at 24 and 48h. EA alone and combined with CIS suppressed MMP2 and MMP9 expression across both cell types. Additionally, EA and CIS + EA treatments suppressed Bcl-2 expression and upregulated Bax expression. Immunocytochemical results aligned with gene expression data, demonstrating reduced protein levels. Molecular docking demonstrated strong binding of EA to Bax and MMP9. These results indicate that EA exerts notable anticancer activity by targeting genes associated with drug resistance, angiogenesis, apoptosis, and metastasis. The findings highlight EA's therapeutic potential in breast cancer treatment, alone or with CIS. Further detailed in vivo and clinical studies are needed to confirm these promising results.

Cisplatin(IV)-fatty acid prodrug-bound albumin nanoparticles: In vitro, in silico, and in vivo evaluation in breast cancer therapy.

To evaluate the IDH1, p53 protein (TP53), epidermal growth factor receptor (EGFR), Ki-67 nuclear antigen, ATP-dependent helicase (ATRX), glial fibrillary acid protein (GFAP), methylated DNA-protein cysteine methyltransferase (MGMT), podoplanin (PDPN), transferrin (TR) in glioblastoma multiforme (GBM) samples. In addition, we investigated whether the expression of protein markers and the response to chemotherapy in vitro are associated with lifespan in patients with GBM. Thirty patients diagnosed with GBM were immunohistochemically (IHC) evaluated for IDH1, TP53, EGFR, Ki-67, GFAP, MGMT, ATRX, PDPN, and TR. The sensitivities of primary GBM cells to chemotherapy temozolomide (TMZ), doxorubicin (DOX), carboplatin (CARB), cisplatin (CIS), and etoposide (ETO) were analyzed by measuring cell viability with the MTT assay. Kaplan-Meier survival analysis was performed using GraphPad Prism software. In this study, we found significant associations between DOX (500μM, p = 0.0446), CARB (3000 μM, p = 0.0015) and CIS (1800 μM, p = 0.0293) with increased lifespan of GBM patients. An association between a combination of Ki-67 expression (>20%) and CARB (3000 μM, p = 0.016) with prolonged lifespan of GBM patients was shown. A relationship between Ki-67, ETO (12μM, p = 0.0032), and an increase lifespan (13.5 vs. 6months) in GBM patients was detected. A combination of ATRX (<60%) and CIS correlated with an increased lifespan for GBM patients (12.5 vs. 4months, respectively, p < 0.05). Combinations of DOX (500μM) and GFAP (<60%) were associated with prolonged lifespan for patients (p = 0.047). The results of the current study suggest that the expressions of IHC markers in combination with the response to chemotherapy for GBM cells may be a good predictor of lifespan patient. Hence, GBM can be grouped into prognostically relevant subgroups using these IHC markers expression signatures individually, as well as the combined with chemotherapy. In vivo drug testing on primary GBM cells in combination with expression of marker proteins can predict tumor response to personalized therapy and lifespan of the patients.

The proposition of the present study was to evaluate the influence of the secondary effect of tamoxifen (TAM) associated with cisplatin (CIS) in the bone remodeling of osseointegrated titanium implants installed in rat tibiae. One hundred female rats underwent bilateral ovariectomy (OVX) and received titanium implants in both tibiae. Six weeks later, animals were treated with tamoxifen (15mg/kg) or saline, with further subdivisions receiving cisplatin (5mg/kg or 2.5mg/kg) or saline. A non-ovariectomized group served as a negative control. Animals were euthanized at 30 and 90 days after treatment initiation. Tibiae were harvested for histometric analysis of bone-to-implant contact (BIC) and bone ingrowth (BIN), histology, and immunohistochemistry (tartrate-resistant acid phosphatase [TRAP], osteocalcin [OCN], and runt-related transcription factor [RUNX2]). Additionally, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were used for ultrastructural and elemental analyses. The groups that received TAM showed higher BIC and BIN, increased expression of RUNX-2 and OCN, and a lower number of TRAP-positive cells. At 30 and 90 days, almost all spaces were filled with vital, well-vascularized bone tissue without inflammatory foci. TAM groups also exhibited an increased calcium/phosphate (Ca/P) ratio compared to their respective controls, and a progressive thickening of collagen fibril bundles was observed in the bone matrix. Tamoxifen positively influenced bone remodeling around osseointegrated titanium implants in rats undergoing cisplatin-based cancer therapy. Dental implant surgery in patients undergoing chemotherapy is frequently approached with caution, as these pharmacological treatments can impair bone metabolism and jeopardize the integration of the implant with the bone. This study investigated whether tamoxifen, a medication widely utilized in breast cancer therapy, could potentially enhance bone healing around titanium implants, specifically when administered alongside the chemotherapeutic agent cisplatin. Utilizing a laboratory model that simulates postmenopausal bone loss, the research demonstrated that tamoxifen significantly improved both the volume and the structural quality of the bone surrounding the implants, partially mitigating the adverse effects associated with cisplatin. These findings are of clinical importance as they suggest that a history of chemotherapy should not be considered a definitive barrier to successful dental rehabilitation. Instead, with appropriate pharmacological support, dental implant procedures may be a more viable and predictable treatment option for cancer survivors than previously recognized. This research provides a foundation for clinicians to better evaluate the feasibility of oral rehabilitation in this patient population, ultimately aiming to improve their long-term oral health and quality of life.

Cisplatin (CIS) remains a cornerstone of chemotherapy but is limited by resistance and systemic toxicity. Combining DNA-damaging agents with epigenetic modulators such as vorinostat (VOR) offers a promising strategy to enhance efficacy. However, the co-delivery of these drugs is challenging due to their distinct physicochemical properties. The aim was to develop and characterize niosomal nanoparticles co-loaded with CIS and VOR (NIO-CIS-VOR) and to assess their physicochemical characteristics and in vitro anticancer activity. Niosomes were prepared using ethanol injection, with CIS entrapped in the aqueous core and VOR in the lipid bilayer. Characterization included particle size, polydispersity index (PDI), and zeta potential by DLS, morphology by TEM, and encapsulation confirmation by FTIR. Encapsulation efficiency (EE%) and drug release were determined by HPLC. Cytotoxicity, caspase-3/7 activation, colony formation, and wound healing assays were conducted in HT-29, A549, and PANC-1 cancer cell lines. Optimized NIO-CIS-VOR nanoparticles exhibited a mean diameter of 152.7 nm, PDI of 0.12, and zeta potential of -9.79 mV, with spherical morphology. Encapsulation efficiency of NIO-CIS-VOR reached 89.3% for CIS and 52.1% for VOR. The formulation showed sustained release over 72 h, with cumulative release of 62% (CIS) and 38% (VOR) at 6 h. Cytotoxicity assays demonstrated markedly reduced IC50 values for NIO-CIS-VOR compared with free drugs: 1.8 µM vs. 4.47 µM (CIS) and 3.4 µM (VOR) in HT-29; 0.95 µM vs. 3.8 µM and 3.1 µM in A549; and 2.37 µM vs. 13.9 µM and 3.66 µM in PANC-1. Enhanced apoptosis and reduced colony formation further confirmed superior anticancer activity.In Conclusion the Co-loaded niosomes achieved efficient co-delivery, sustained release, and synergistic anticancer effects, highlighting NIO-CIS-VOR as a promising nanocarrier for combination cancer therapy.

Cisplatin (CIS) is a highly effective chemotherapeutic agent widely used to treat solid tumors. However, its clinical use is significantly limited by dose-dependent hepatotoxicity, characterized by hepatocellular injury and apoptosis. Despite extensive research efforts, an effective pharmacological strategy to reduce CIS-induced liver dysfunction remains elusive. Sacubitril/valsartan (VS), an angiotensin receptor-neprilysin inhibitor, has shown cytoprotective and anti-apoptotic effects in various models of organ toxicity. However, its ability to protect against CIS-induced liver damage has not been thoroughly studied. This research aimed to assess the hepatoprotective potential of VS in rat models of cisplatin-induced liver toxicity, focusing on oxidative markers including reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the roles of caspase-3 inhibition and modulation of retinoid X receptor-alpha (RXR-α) in its mechanism. In this study, adult male Wistar rats were randomly assigned to four groups: control, VS-treated, cisplatin-treated, and CIS + VS co-treated. Hepatotoxicity was induced by administering cisplatin at 8mg/kg via intraperitoneal injection, repeated over three cycles. Meanwhile, VS was given orally at 60mg/kg daily for 10 days. Liver biochemical markers, including ROS, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), total bilirubin (TBIL), and lactate dehydrogenase (LDH), were measured using ELISA. Liver tissue was examined histologically with hematoxylin and eosin staining, and the expression of caspase-3 and RXR-α was evaluated through immunofluorescence. Cisplatin administration significantly increased ROS, MDA, ALT, AST, ALP, TBIL, and LDH levels, while decreasing TP and ALB, indicating severe liver dysfunction. Histopathology showed extensive hepatocellular degeneration, necrosis, and inflammation. Co-treatment with VS significantly normalized liver function tests, improved protein levels, and maintained normal liver histology. Additionally, VS markedly reduced caspase-3 immunoreactivity while increasing RXR-α expression compared to CIS alone. Sacubitril/valsartan appears to protect the liver from cisplatin toxicity, primarily by inhibiting oxidative stress and apoptosis through caspase-3 suppression, and modulating RXR-α signaling. These results provide new insights into the mechanisms involved and suggest that VS may be a promising adjunct therapy to lessen cisplatin-induced hepatotoxicity during chemotherapy.

Nigella sativa oil (NSO): A game-changing neurorestorative strategy in cisplatin neurocognitive toxicity.

Cisplatin (CP)-induced nephrotoxicity is a major clinical concern. Emerging evidence has revealed the critical role of PANoptosis, a coordinated cell death pathway, and neutrophil extracellular traps (NETs) in renal tubular damage. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) has been recognized as a potential modulator of inflammation and cell survival; however, its regulatory function and mechanism in acute kidney injury (AKI), especially CP-induced AKI, particularly concerning NETs and PANoptosis, remain poorly understood. This study investigates the central role of PPARγ and explores the therapeutic potential of its novel activator, O-alkyl and o-benzyl hesperetin derivative-1 L (HD-1L), in this context. Cultured renal tubular epithelial cells (mTECs) as well as a CP-induced AKI mouse model (20mg/kg, 72h) and renal ischemia-reperfusion injury (IRI) model​ were used. PPARγ heterozygous knockout mice, NET inhibitors (DNase I and GSK484), and pharmacological interventions (including the novel PPARγ agonist HD-1L and rosiglitazone [ROSI]) were used. The molecular mechanisms were assessed using western blotting, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and cellular thermal shift assays (CETSA). PPARγ activity, NET markers (MPO, Cit-H3, and dsDNA), PANoptosis-related proteins (p-MLKL, GSDMD-N, and cleaved caspase-3), and reactive oxygen species (ROS) levels were quantified. CP triggered robust PANoptosis in the renal tissues, accompanied by elevated NETs and ROS-dependent NETosis. PPARγ activation significantly suppressed ROS production in neutrophils, thereby reducing NET formation. Mechanistically, NETs facilitate the release of cytoplasmic dsDNA, activate the AIM2 inflammasome, and promote PANoptosome assembly. Genetic PPARγ heterozygous knockout exacerbated renal injury and abolished protective effects, confirming the central role of PPARγ. HD-1L-induced activation of PPARγ reduced markers of PANoptosis and improved renal function in CP-AKI models. Furthermore, PPARγ agonism similarly protected against renal injury and suppressed the NETosis-PANoptosis axis in the IRI model. PPARγ is a pivotal checkpoint in CP-AKI by inhibiting ROS-NETosis-driven AIM2-mediated PANoptosis. This protective mechanism is also applicable to IRI-induced AKI, highlighting its broad relevance. HD-1L confers renoprotection through PPARγ activation, providing a novel therapeutic strategy against AKI.

Cisplatin (CSP) is a first-line chemotherapeutic for laryngeal squamous cell carcinoma (LSCC), but its clinical effectiveness is limited by resistance and toxicity. Hesperidin (HESP), a citrus flavonoid, may enhance chemotherapeutic efficacy through pro-apoptotic properties. This study investigated the involvement of the transient receptor potential melastatin-2 (TRPM2) channel in the HESP-mediated potentiation of CSP-induced cytotoxicity in human laryngeal carcinoma (Hep-2) cells. Hep-2 cells were treated with CSP (25 µM), HESP (25 µM), or their combination for 24 h. The findings showed that the combined application of HESP and CSP reduced cell viability by approximately 50% (p < 0.001), which was the lowest compared to CSP alone. Western blot analysis revealed that TRPM2 protein expression was higher in the CSP+HESP group compared to the control group (p < 0.001). This synergistic treatment resulted in an increase in ROS production and a decrease in MDA levels, accompanied by a reduction in cellular GSH levels (p < 0.001). Furthermore, the combination therapy increased pro-inflammatory cytokines such as IL-1β and TNF-α (p < 0.001). Functional analyses showed that HESP treatment enhanced CSP-induced Ca2+ influx and altered mitochondrial membrane potential (p < 0.001). The pharmacological inhibition of TRPM2 with ACA and 2-APB reversed these effects, restoring redox balance and reducing cellular damage. In conclusion, HESP amplifies CSP-induced apoptosis in Hep-2 cells through TRPM2-dependent oxidative stress, Ca2+ dysregulation, and mitochondrial dysfunction. These findings identify TRPM2 as a mechanistic mediator of HESP-enhanced chemosensitivity in LSCC.

Cisplatin (CIS) is a commonly utilized chemotherapeutic agent, but its use is often accompanied by adverse effects such as neurotoxicity and cognitive impairments, collectively referred to as chemobrain. This condition impacts over 70% of cancer survivors, and currently, there are no established therapeutic interventions. This study aimed to evaluate the efficacy of tirzepatide in mitigating the neuropathy effects induced by cisplatin therapy. Forty female Wistar albino rats were divided into four groups of ten: control (untreated), cisplatin (CIS), tirzepatide (TIRZ), and CIS/TIRZ. Treatments were administered intraperitoneally in two injections. The CIS group received cisplatin at a dosage of 5 mg/kg, while tirzepatide was administered at 1.35 mg/kg. In the CIS/TIRZ group, tirzepatide (1.35 mg/kg) was administered prior to cisplatin (5 mg/kg), with a 3-h interval between the two treatments. Post-treatment, behavioral assessments (Y-maze) and oxidative stress biomarkers were evaluated, including enzymatic antioxidants catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx-1), as well as oxidative damage markers such as reactive oxygen species (ROS) and malondialdehyde (MDA). Survival rates were 90% in both the TIRZ and CIS groups, and 70% in the CIS/TIRZ group, whereas all rats in the control group survived. All treatment groups experienced a reduction in body weight compared to the control group. Cisplatin administration resulted in impaired learning and memory in the Y-maze test, which was linked to decreased levels of the antioxidants GPx-1 and catalase, with no alteration in SOD levels. Additionally, ROS and MDA levels were slightly elevated in the CIS and TIRZ groups individually. Although tirzepatide did not ameliorate the memory deficits or antioxidant reductions caused by cisplatin, it did lead to a reduction in ROS and MDA levels. CIS therapy accelerates memory deficits in female rats by increasing oxidative stress. However, TRIZ did not alleviate the memory deficits or antioxidant reductions, although it did reduce ROS levels.

Cisplatin (CP) and carboplatin (CBP), two key platinum‑based anticancer drugs, face clinical limitations that prompt the search for new strategies to enhance efficacy and reduce toxicity. This study applies density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), molecular docking, and spectroscopic analyses to explore possible synergistic effects of cisplatin-carboplatin [CP-CBP] complexes in breast and cervical cancers. Structural optimizations show small bond‑length adjustments in the [CP-CBP] complexes, which strengthen intermolecular interactions and overall stability. Thermodynamic analyses confirm their exothermic nature (ΔH < 0), indicating thermodynamic stability, while adsorption energies (Ead = -14.69, -12.47, -14.27kcal/mol for States I, II, III) suggest enhanced bioavailability and controlled release in aqueous environments, though higher gas-phase energies indicate stronger interactions. Quantum descriptors, including electrophilicity index (ω) and chemical potential (μ), reveal increased reactivity and improved drug-target interactions, supporting enhanced anticancer potential. Spectroscopic analyses (UV-Vis, IR) confirm altered electronic transitions, reinforcing stability and reactivity changes. Molecular docking indicates that [CP-CBP] complexes outperform individual CP and CBP, with State III achieving -3.75kcal/mol (Ki = 1.78μM) for aromatase and State II -5.48kcal/mol (Ki = 96.86μM) for HER2. CBP stabilizes CP, preventing degradation, enhancing solubility, and enabling controlled release, reducing toxicity. These findings highlight [CP-CBP] complexes as a promising platinum‑based chemotherapeutic strategy with potentially improved pharmacokinetics, warranting further in vitro and in vivo validation for targeted cancer therapy.

One of the most crucial approaches to treating some aggressive diseases, like cancer, is to either discover new medications or to refine and adapt those that already exist. Among these approaches is the drug delivery system, which could help reduce drug doses and side effects. In the existing endeavor, cisplatin (CIS) was loaded on polyvinyl alcohol/polyethylene oxide nanofiber (PVA-PEO-CIS) by the electrospinning method. The fabricated nanofiber was characterized, and its anticancer impact against cervical cancer cells (HeLa) was measured. Also, its antibacterial effect was studied. The obtained findings indicated that (PVA-PEO-CIS) nanofiber inhibits HeLa growth with a half-maximal inhibitory concentration (IC50) of 19.82µg/mL compared to free CIS (IC50 = 26.31µg/mL). Importantly, the nanofiber was less toxic to normal WI-38 cells compared to free CIS. The improvement of the anticancer action of CIS was consistent with CIS release studies that indicated about 50% of CIS was released from nanofibers within 8h. Further, PVA-PEO-CIS nanofiber showed potent bactericidal impact against different bacterial strains, including Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. For several biological applications, including tumor therapy and antibacterial research, PVA-PEO-CIS may be a potential medication candidate.

Acute kidney injury (AKI) is a common clinical syndrome. Chlorogenic acid (CGA) is a natural polyphenol with antioxidant and anti-inflammatory properties. In this study, 60 male Kunming mice were randomly assigned to 6 groups: Control (CON), Cisplatin (CIS), CGA, CIS + CGA, CIS + furosemide (FUR), and FUR. Kidney injury markers, inflammatory indicators, antioxidant enzyme activities, oxidative products, antioxidant proteins, and kidney morphology were assessed using ELISA, histology, and Western blot. Preventive CGA supplementation significantly reduced levels of creatinine (Cr), BUN, KIM-1, and MDA, while restoring the enzymatic activities of SOD, GSH-Px, CAT, and T-AOC. CGA also increased the expression of Nrf2 and GCLC proteins and decreased the expression of Keap1 protein. Levels of IL-1β, IL-2, and IL-6 were reduced, while IL-10 levels were elevated. These results indicate that preventive CGA supplementation effectively mitigates CIS-induced AKI by enhancing antioxidant capacity, attenuating inflammatory responses, and ameliorating kidney structural damage.

HSA bioconjugates with cisplatin, oxaliplatin, and auranofin showed distinct cytotoxicity profiles, highlighting Pt vs . Au differences in cancer cells.

Background: Acute kidney injury (AKI) is a severe and prevalent nephrotic syndrome which lack of definitive therapies. Alpha-amino-β-carboxymuconic acid-ε-semialdehyde decarboxylase (ACMSD) is a metabolic enzyme mainly expressed in the kidney which exacerbated AKI injury by promoting TCA cycle and inhibiting nicotinamide adenine dinucleotide (NAD+) production, whereas lack of effective intervention strategies for ACMSD-targeted therapy.Methods: Herein, we knocked out ACMSD in vitro through CRISPR-Cas9 method, and developed a reactive oxygen species (ROS)-responsive neutrophil-derived cellular vesicles (CVs) drugs (RNAi@ROS-CVs), which efficiently mediated ACMSD knockdown in vivo, exploring the mechanism of ACMSD-induced ferroptosis process in AKI.Results: ACMSD knockout effectively alleviated cisplatin (CP)-induced mitochondrial damage, suppressed TCA cycle progression, promoted NAD+ synthesis, and inhibited ferroptosis in HK2 cells. In mice AKI model, RNAi@ROS-CVs effectively targeted the injured kidneys, downregulated ACMSD expression in renal tubular epithelial cells, reduced ROS production and lipid peroxidation, and alleviated CP or ischemia/reperfusion (I/R)-induced ferroptosis.Conclusion: These findings highlight the therapeutic potential of ACMSD-targeted knockout in AKI intervention and introduce a versatile and efficient controlled-release drug delivery platform for AKI-targeted therapy, with potential applicability to other acute renal diseases.

The rise of antimicrobial resistance to current antibiotics has driven researchers to discover novel natural compounds with antibacterial properties. This study established a sustainable approach for the biofabrication of gold nanoparticles (GNPs) utilizing Ephedra alata leaf extracts conjugated with environmentally friendly, less-toxic, and chitosan (CS), resulting in chitosan (CS)-loaded gold nanoparticles (CS@GNPs). The characterization of GNPs and CS@GNPs is performed using Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and DLS measurements. This investigation evaluated the antioxidant and antibacterial properties of the agar diffusion technique using human pathogens. The IC50 values for ABTS and DPPH were 12.15 ± 0.031μg/mL and 22.14 ± 0.51μg/mL for CS@GNPs. The maximal inhibition of CS@GNPs was 32, 31, 30, and 29mm at a dose of 200μg/mL of CS@GNPs against E. coli, K. pneumoniae, S. aureus, and P. aeruginosa. CS@GNPs demonstrated a superior reduction of MDR bacteria compared to GNPs alone. The anticancer activity showed that the liver HepG2 cancer cell lines exhibited greater sensitivity to the toxicity of CPT + GNPs and CPT + CS@GNPs than non-cancerous fibroblast 3T3 cells. The IC50 values of CPT + GNPs and CPT + CS@GNPs of HepG2 cancer cell lines were 44.32 and 33.15μg/mL. The research indicates that GNPs and CS@GNPs, in conjunction with CPTGNPs, can efficiently combat cancer at doses where the cisplatin (CPT) proves ineffective, resulting in a significant decrease in the necessary dosage for observed antitumor efficacy.

This study aimed to investigate the immunohistochemical expression patterns of proliferating cell nuclear antigen (PCNA), heat shock protein-70 (HSP-70), and kisspeptin-1 (KISS-1), as well as the gene expression levels of nuclear factor erythroid 2–related factor 2 (NRF2), heme oxygenase-1 (HO-1), tumor necrosis factor-alpha (TNF-α), and caspase-3 (CAS-3) in cisplatin (CIS)-induced ovarian toxicity, and to evaluate the protective effects of dapagliflozin (DAPA). Thirty-two female Wistar albino rats (n = 8 per group) were divided into four groups: Control, CIS (7.5 mg/kg, intraperitoneal), CIS + DAPA (10 mg/kg DAPA, oral for 7 days + CIS), and DAPA alone. Ovarian tissues were harvested for immunohistochemical and genetic evaluations. PCNA, HSP-70, and KISS-1 immunoreactivities were semi-quantitatively scored, and the mRNA expression levels of NRF2, HO-1, TNF-α, and CAS-3 were assessed using real-time quantitative PCR. All results were statistically analyzed. CIS administration led to a marked increase in PCNA, HSP-70, and KISS-1 immunoexpression, along with downregulation of NRF2 and HO-1 and upregulation of TNF-α and CAS-3 gene expressions (p < 0.001 for all) compared to the control group, indicating enhanced cellular proliferation, oxidative stress, inflammation, and apoptosis. In the CIS + DAPA group, a significant attenuation in PCNA (p < 0.001), HSP-70 (p < 0.001), and KISS-1 (p < 0.001) expression levels, and a reversal of genetic alterations were observed compared to the CIS group, demonstrating that DAPA mitigated proliferative, stress-associated, inflammatory, and apoptotic changes induced by CIS expressions (p < 0.001 for all). Ovarian tissues in the DAPA-alone group maintained expression profiles similar to the control. DAPA exerts protective effects against CIS-induced ovarian damage by modulating proliferation, cellular stress, inflammation, and apoptotic pathways, as evidenced by the downregulation of PCNA, HSP-70, KISS-1, TNF-α, and CAS-3, and upregulation of NRF2 and HO-1. These findings suggest that DAPA may offer a novel therapeutic approach for preserving ovarian function in patients undergoing chemotherapy.