Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1β, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-β1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential

Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails

Aims: Considering the role of cyclooxygenases (COX) in placental programming induced by preeclampsia (PE), we investigated whether gestational exposure to nonsteroidal antiinflammatory drugs (NSAIDs) with different COX-1/2 selectivity would variably modulate pre- and postnatal (weaning time, i.e. 3 weeks after delivery) cardiovascular manifestations of PE. Materials and methods: PE was induced by oral administration of Nω-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day for 7 days) to pregnant rats starting from day 14 of gestation. Rats were treated simultaneously with celecoxib (10 mg/kg/day), diclofenac (0.5 mg/kg/day), or naproxen (1 mg/kg/day). Key findings: Tail-cuff measurements revealed a higher systolic blood pressure (SBP) in PE mothers at gestational day 20 (GD20). More exaggerated rises in prenatal SBP were noted in PE rats treated with celecoxib but not diclofenac or naproxen. Higher levels of serum creatine and kinase MB (CK-MB), a biomarker of cardiac damage, were demonstrated in weaning PE rats and this effect was suppressed by naproxen only. Additionally, naproxen was the most effective among all 3 NSAIDs in diminishing the PE-induced surges in (i) cardiomyocyte cross-sectional area, (ii) cardiac COX-1/COX-2 activities, (iii) arachidonate metabolites (PGE2, PGF2α, and TXA2), (iv) caspase-3 and beclin-1 expressions. By contrast, the PE-related increments in cardiac expression of antiangiogenic (sFlt-1, and endoglin-1) and inflammatory (nuclear factor kappa B, NF-κB) factors were indiscriminately reduced by all NSAIDs. Significance: Compared with celecoxib or diclofenac, naproxen appears to be the most advantageous in minimizing cardiac damage in weaning PE rats due to its synchronized downregulatory effects on cyclooxygenase, apoptotic, and autophagic pathways

Quercetin Abrogates Oxidative Neurotoxicity Induced by Silver Nanoparticles in Wistar Rats

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1β, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue