Cisplatin (CIS) is an effective chemotherapeutic agent whose clinical use is limited by off-target toxicity, including damage to ovarian granulosa cells, characterized by oxidative stress and inflammation. Here, the cytoprotective potential of the citrus flavonoids, naringin (NG) and hesperidin (HP), was investigated in ovarian granulosa cells exposed to CIS-induced toxicity. Molecular docking demonstrated that NG and HP exhibited strong binding affinities for key antioxidant, nuclear factor erythroid 2–related factor 2 (Nrf2) and catalase (CAT) as well as anti-apoptotic B-cell lymphoma-2 (Bcl-2) proteins, while CIS preferentially interacted with pro-apoptotic targets. In vitro, CIS dose-dependently reduced cell viability and hormone secretion (progesterone and estradiol), and these reductions were significantly restored by co-treatment with NG or HP. CIS-induced oxidative injury, marked by elevated accumulation of reactive oxygen species (ROS), lipid peroxidation, and depletion of reduced glutathione (GSH), as well as key antioxidant defenses (superoxide dismutase (SOD) and catalase (CAT), was effectively mitigated by the NG and HP. Furthermore, NG and HP suppressed the CIS-triggered inflammation by inhibiting NF-κB activation and downregulating the release of major pro-inflammatory mediators (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, IL-1β). They also counteracted CIS-induced apoptosis by reducing phosphorylation of protein kinase B (Akt), cytochrome c (Cyt c) release, caspase (Cas) activation, and the Bcl-2-associated X protein (Bax)/Bcl-2 ratio. These findings demonstrated that NG and HP could protect ovarian granulosa cells from CIS-induced damage through dual regulation of the Nrf2/heme oxygenase-1 (HO-1) antioxidant and nuclear factor kappa B (NF-κB) inflammatory axis, highlighting their potential as adjuvant therapies to mitigate chemotherapy-induced ovarian toxicity.
Ahmed Abdeen, Obeid Shanab, Mohammed H. Hassan et al.· Frontiers in Pharmacology· 0 citations
This work investigates the potential protective effects of the diatom Amphora coffeaeformis as a feed additive against the deleterious effects (primarily on immune organs) of cypermethrin (CYP) in Nile tilapia, Oreochromis niloticus, with respect to hematology, immune/antioxidant parameters, biochemical indices, proinflammatory and apoptotic regulatory genes, and tissue architecture. For subacute exposure, a total of 240 healthy O. niloticus (30 ± 2.5 g) were allocated into four groups in triplicate (20 fish/replicate). The control and AMP groups were fed a basal diet and a 5% A. coffeaeformis supplement, respectively. The CYP and AMP+CYP groups were fed a basal diet and a 5% A. coffeaeformis supplement, respectively, and exposed to sublethal concentrations of CYP for 21 days. A substantial decrease in hematological indices (RBCs, Hb, PCV, and WBCs) and immune/antioxidant parameters (phagocytic and respiratory burst activities, GSH, TAC, SOD, and CAT) was observed with CYP exposure. Additionally, notable increases were observed in serum levels of hepatorenal indicators (ALT, AST, ALP, urea, creatinine, and uric acid), the lipid profile (cholesterol and triglycerides), the MDA lipid peroxidation biomarker, and pro-inflammatory IL1β and apoptotic Cas3 gene expression. Furthermore, hepatic and splenic tissues were severely affected by CYP exposure. Feeding CYP-exposed fish an A. coffeaeformis diet significantly improved hematological indices, immune/antioxidant status, hepatorenal function, and lipid profile, and decreased expression of the stress protein HSP70 and pro-inflammatory cytokines (IL1β, TNFα, and CC1- chemokine) and the apoptotic Cas3 gene compared with CYP-exposed fish. Additionally, tissue architecture improved following A. coffeaeformis supplementation. Overall, A. coffeaeformis diets could be enriched as a feed supplement in the O. niloticus diet to alleviate adverse effects on fish health and immune response during CYP exposure.
Elsayed A. A. Eldessouki, G. Elshopakey, Mai A. M. El‐Son et al.· Developmental and Comparativ...· 0 citations
