Novel insights into the synergistic effects of selenium nanoparticles and metformin treatment of letrozole - induced polycystic ovarian syndrome: targeting PI3K/Akt signalling pathway, redox status and mitochondrial dysfunction in ovarian tissue.

PURPOSE: Polycystic ovary syndrome (PCOS) has a series of reproductive and metabolic consequences. Although the link between PCOS, IR, and obesity, their impact on the pathogenesis of PCOS has yet to be determined. Dysfunction of PI3K/AKT pathway has been reported as the main cause of IR in PCOS. This study purposed to explore the effects of selenium nanoparticles (SeNPs) alone and combined with metformin (MET) in a PCOS-IR rat model. METHODS: After 3 weeks of treatment with SeNPs and/or MET, biochemical analysis of glycemic & lipid profiles, and serum reproductive hormones was performed. Inflammatory, oxidative stress, and mitochondrial dysfunction markers were determined colormetrically. The expression of PI3K and Akt genes were evaluated by Real-time PCR. Histopathological examination and Immunohistochemical analysis of Ki-67 expression were performed. RESULTS: The results showed that treatment with SeNPs and/or MET significantly attenuated insulin sensitivity, lipid profile, sex hormones levels, inflammatory, oxidative stress and mitochondrial functions markers. Additionally, PI3K and Akt genes expression were significantly upregulated with improved ovarian histopathological changes. CONCLUSION: Combined SeNPs and MET therapy could be potential therapeutic agent for PCOS-IR model via modulation of the PI3K/Akt pathway, enhancing anti-inflammatory and anti-oxidant properties and altered mitochondrial functions.HighlightsThe strong relationship between obesity, insulin resistance, and polycystic ovarian syndrome.Disturbance of the PI3K/Akt signaling pathway is involved in the progression of polycystic ovary syndrome-insulin resistance (PCOS-IR).In PCOS-IR rats, combined SeNPs and metformin therapy considerably alleviated IR by acting on the PI3K/Akt signaling pathway.The combination of SeNPs and metformin clearly repaired ovarian polycystic pathogenesis and improved hormonal imbalance in PCOS-IR rats.

The Possible Role of Naringenin in the Prevention of Alcohol-Induced Neurochemical and Neurobehavioral Deficits.

Chronic alcohol consumption is associated with progressive/irreversible neurodegeneration. However, there is not a clear understanding of its discrete pathophysiology or therapeutic intervention. The present study aimed to investigate the protective effect of the natural citrus flavonoid, naringenin (NAG), against alcohol-induced neurodegeneration in the brain cerebral cortex. Thirty-two male albino rats were randomly divided into four equal groups (eight rats each): control group (I); NAG-treated group (II); alcohol-intoxicated group (III) and alcohol + NAG co-treated group (IV). Brain nuclear factor erythroid 2-related factor 2 and receptor-interacting protein kinase 3 expression were assessed by real-time polymerase chain reaction. NAD(P)H quinone oxidoreductase 1 activity and malondialdehyde, reduced glutathione, mixed lineage kinase-like protein, phosphorylated glycogen synthase kinase 3 beta, and ciliary neurotrophic factor levels were all measured biochemically. B-cell lymphoma 2 expression was assessed by immunohistochemistry. A histopathological examination and neurobehavioral tests were performed. The alcohol-treated group showed a significant increase in oxidative stress and necroptosis biomarkers with a significant reduction in neuroprotective proteins. NAG co-administration effectively ameliorated cognitive dysfunction with an apparent neuroprotective effect by targeting various signaling pathways, including nuclear factor erythroid 2-related factor/NAD(P)H quinone oxidoreductase 1, anti-oxidant capacity, attenuated necroptosis, and upregulated neuroprotective ciliary neurotrophic factor. The study findings suggest NAG as a possible management strategy for alcohol-induced neurodegeneration.

Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF-κB intricate network in experimentally doxorubicin-induced cardiotoxicity in rats: The role of curcumin.

Doxorubicin (DOX) is an important chemotherapeutic drug. Cardiotoxicity diminishes its clinical efficacy. We aimed to focus on the mechanism of DOX-induced cardiotoxicity, in addition, to evaluate curcumin's protective effect against it. Twenty-eight rats were divided into the normal control group I, curcumin-treated (200 mg/kg body weight [b.w.]) group II, DOX-treated (4 mg/kg b.w.) group III, and DOX + curcumin group IV. Cardiac injury markers, heart tissue oxidative stress indices, interferon-gamma (INF-γ), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), upregulated modulator of apoptosis (PUMA), p53 and nuclear factor kappa-B p65 (NF-κB p65) levels as well as messenger RNA gene expression of Rac1 and fibroblast growth factor-inducible protein 14 (Fn14) were assayed, besides the assay of DNA damage, histopathological changes, survivin immunohistochemistry and electron microscopic examination. Curcumin significantly downregulated Rac1 and Fn14 gene expression and significantly decreased p53, NF-κB p65, INF-γ, and PUMA levels in the cardiac tissue. In addition, curcumin improved oxidative stress indices, DNA damage, and cardiac toxicity markers in the form of lactate dehydrogenase (LD), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin-I (cTn-I). Meanwhile, upregulated antiapoptotic marker survivin was observed. Light and electron microscopic findings confirmed our biochemical and molecular outcomes. The current study established the antioxidant, anti-inflammatory, and antiapoptotic roles of curcumin against DOX cardiotoxicity.