Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

Background: This study investigated the renoprotective potential of Nano-Cilostazol against cisplatin (CIS)-induced renal injury in male rats and explored its molecular mechanisms. Our results showed that Nano-Cilostazol has a favorable physicochemical characteristic, including a mean particle size of approximately 101 nm, narrow polydispersity, and high stability. FTIR analysis indicated successful drug entrapment, preserving functional groups and enhancing hydrogen bonding. Docking analysis showed that cilostazol had stronger binding affinities than disulfiram against seven acute kidney injury-related targets. Interaction profiling confirmed stable binding through hydrogen bonding, hydrophobic, and π-interactions with BAX, ASC, GSDMD, KIM-1, JAK2, NLRP3, and miRNA-155. In vivo, CIS administration led to marked renal dysfunction, showing up as significant elevations in serum urea, creatinine, cystatin-C, CRP, and NGAL which indicated by severe histopathological damage. Co-treatment with Nano-Cilostazol significantly lessened renal functional impairment biochemically and histopatologically. Nano-Cilostazol markedly reduced lipid peroxidation and oxidized glutathione while also restoring antioxidant defenses like superoxide dismutase and catalase, with total and reduced glutathione. Additionally, Nano-Cilostazol attenuated renal inflammation, inhibiting NF-κB activation, lowering pro-inflammatory cytokines (TNF-α and IL-1β), and downregulating inflammatory and injury-related genes. CIS-triggered apoptotic signaling was also mitigated, shown by increased caspase-3 and BAX expression with downregulation of BCL-2. Nano-Cilostazol significantly inhibited apoptosis and pyroptosis (NLRP3, ASC, GSDMD)-related pathways, modulated JAK2/STAT3 signaling, and downregulated miRNA-155 expression. In conclusion, Nano-Cilostazol offers potent protection against cisplatin-induced nephrotoxicity.

Background: The constitutively activated oncogenic signals of ERK, β-catenin, and signal transducer and activator of transcription-3 (STAT-3) are therapeutic targets in cancer treatment. The present study explored the anticancer mechanism of grape seed extract's polyphenolic compounds, Oligomeric-Proanthocyanidins (OPC-PACs), to combat oncogenic proliferative signaling crosstalk, as the precise mechanisms are not yet fully understood. Materials and Methods: The mechanistic anti-cancer effects of the OPC-PACs on oncogenic signaling crosstalk and apoptosis-induction were investigated, using liver and breast cancer cell lines (HepG2 and ZR-75-1), in vitro and by measuring tumor volume of MNU-induced mammary tumors, in vivo. Results: Wst-1 assay demonstrated that the viability of OPC-PACs treated cells was significantly decreased in a concentration-dependent manner compared to the mock. The calculated IC50 was (63.1 ± 0.024 mg/ml) and (61.6 ± 0.016 mg/ml) for HepG2 and ZR-75-1, respectively. Furthermore, OPC-PAC treatment for 48 h induced cell morphological changes, histone release, increased caspase-3 activity, and inhibition of p-ERK, β-catenin, and STAT-3 expression with apoptosis induction in HepG2 and ZR-75-1 cell lines as well as inhibition of tumor volume in vivo. In vivo, OPC-PAC treatment for 45 days significantly (p < 0.05) decreased the tumor size of MNU-induced mammary tumors by 28.7% compared to untreated-induced tumors. In-vivo cytotoxicity assessment confirmed the safety of the OPC-PACs treatment. Conclusion: The present study introduces OPC-PAC extract as a natural, non-toxic, and significantly inhibited crosstalk involved in cell proliferation that might act as a promising protective compound for consideration in complementary therapy in human cancers.