Human & experimental toxicology最新文献

BackgroundGold nanoparticles (Au NPs) have emerged as major contributors for innovative technologies and have been used extensively in various biomedical and industrial fields with little, if any, known about their neurotoxicity.ObjectiveThe current study aims to explore the nanotoxicity of Au NPs on the brain tissues.Materials and methodsTwo experimental groups, a control one and an Au NPs-treated group, each comprising 10 adult male Wistar albino rats, were used. Nanoparticle-treated rats received 28 intraperitoneal injections of 10 nm Au NPs at a daily dosage of 2 mg/kg.ResultsBrain tissue specimen for each rat under study was subjected to histological, immunohistochemical, and morphometric examination for alterations that might be induced by Au NPs exposure. Compared with control animals, brain tissue of rats treated with Au NPs exhibited neuronal shrinkage and pyknosis, perineuronal spacing, glial cell proliferation, vascular congestion, and neurons with lipofuscin pigmentation. Moreover, the hippocampus exhibited shrunken neurons, vascular congestion, and perivascular edema. Furthermore, the cerebellum showed degenerated Purkinje cells, cerebellar congestion, and perivascular spacing. In addition, the neuronal tissue demonstrated decreased autophagy, astrogliosis, and apoptosis presented by substantially decreased immunohistochemical protein expression of Beclin 1, increased expression of GFAP and caspase 3, respectively.ConclusionThe findings suggest that exposure to Au NPs has the potential to cause histological, immunohistochemical, and morphometric changes in brain tissue, which could impact the function of this vital organ. Further endeavors are necessary for more understanding of the potential risks of Au NPs to human health.

Introduction: Quercetin has been reported to inhibit the growth of oral squamous cell carcinoma (OSCC), but the mechanism remains unclear. Therefore, our study aimed to investigate the involvement of sirtuin 3 (SIRT3) and the autophagy-dependent form of cell death, ferroptosis, in the pathogenesis of OSCC, and observe the impacts of quercetin on ferroptosis and SIRT3/AMPK/mTOR-mediated autophagy.

Methods: SIRT3 knock out or overexpressing SCC15 cell line was generated, treated with indicated drugs, and malondialdehyde (MDA) and ROS levels were measured. Roles of SIRT3 in regulating autophagy-mediated ferroptosis were assessed by immunoprecipitation and Western blotting.

Results: SIRT3 overexpression increased levels of MDA and ROS, reducing cell viability, and SIRT3 knockout produced the opposing effect. SIRT3 overexpression upregulated ATG16L1 expression and the conversion of LC3-Ⅰ to LC3-Ⅱ, triggering autophagy. Suppression of autophagy by ATG16L1 knockout impaired SIRT3-triggered ferroptosis. Use of an AMPK inhibitor antagonized the induction of ferroptosis by SIRT3 in SCC15 cells, indicating the involvement of the AMPK/mTOR pathway. Additionally, quercetin significantly increased the levels of SIRT3, p-AMPK, ATG16L1, and the ratio of LC3-Ⅱ/Ⅰ, but reduced cell viability and p-mTOR in SCC15 cells. Autophagy and AMPK inhibitors, or SIRT3 deletion significantly antagonized the impacts of quercetin on the autophagy-mediated ferroptosis in cancer cells.

Discussion: SIRT3 overexpression activated the AMPK/mTOR pathway and triggered ATG16L1-mediated autophagy, promoting ferroptosis in SCC15 cells, and we proposed that quercetin may be a promising therapeutic drug for OSCC.

IntroductionThis study examined the cardioprotective effects of Pelargonidin-3-O-glucoside (Pg3G) against myocardial infarction induced by isoproterenol (ISO) in male Wistar rats.MethodsAnimals were divided into four groups each groups contain six animals. Group 1 control; Group 2 Pg3G treated control; Group 3 ISO-control; Group 4 Pg3G + ISO treated rats. At the end of the experiment period the animals were sacrificed and collected the serum, heart tissue used for the experimental work.ResultsAccording to the network pharmacology analysis, Prostaglandin-endoperoxide Synthase 2 (PTGS2), Matrix metallo proteins -9 (MMP-9), and tumour necrosis factor-alpha (TNF-α) were identified as potential targets among the 97 common targets between Pg3G and myocardial injury. Further, we investigated that prominent cardiac indicator such creatine kinase (CK), CK-MB, cardiac troponin T (cTnT), and cardiac troponin I (cTnI) were not elevated by ISO in the presence of Pg3G administration. Additionally, Pg3G administration decreased the pro-inflammatory cytokines generated by ISO, including as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and TNF-α, suggesting its anti-inflammatory qualities. Additionally, Pg3G increased levels of reduced glutathione (GSH) and restored the activity of important antioxidant enzymes that were depleted by ISO-induced oxidative stress, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD).DiscussionPg3G capacity to reduce ISO-induced inflammatory, fibrotic, and cardiac toxicity markers in myocardial tissue was demonstrated by gene expression investigations. Therefore, Pg3G may be considered for ISO-induced cardiac injury since it provides significant cardioprotection by reducing oxidative stress, inflammation, and fibrosis.

BackgroundCisplatin (CIS) is a widely used chemotherapeutic agent; however, it is associated with ovarian toxicity. Tribulus Terrestris (TT) is recognized for its antioxidant and anti-inflammatory properties. This study aims to evaluate the effects of TT extract on ovarian tissue damage induced by cisplatin.Material and MethodTwenty-five female BALB/c mice were divided into five groups (n = 5): Control, CIS (Cisplatin only), CIS + TT100 (100 mg/kg TT extract daily + CIS), CIS + TT300 (300 mg/kg TT + CIS), and CIS + TT500 (500 mg/kg TT daily + CIS). After 15 days, blood samples were collected for hormonal analysis, and ovaries were harvested for histopathological, immunohistochemical, and biochemical assessments.ResultsThe CIS group exhibited a significant decline in follicle count compared to the control group (P < 0.001). In contrast, the CIS + TT groups showed a notable increase in follicle count (P < 0.05). TT treatment also resulted in significant improvements in antioxidant markers (SOD, CAT) and a reduction in oxidative stress (MDA) compared to the CIS group. Moreover, E2, AMH, and progesterone concentrations were decreased in the CIS group, while these levels were restored in the TT-treated groups (P < 0.001). The expression of inflammatory markers TNF-α and IL-1β was higher in the CIS group and decreased in the TT-treated groups.ConclusionTribulus Terrestris extract effectively mitigates cisplatin-induced ovarian toxicity by enhancing follicular count, improving antioxidant activity, and reducing oxidative stress. TT treatment also elevated AMH and progesterone levels while decreasing inflammatory markers, underscoring its potential as a protective agent against cisplatin-induced ovarian damage.

IntroductionSodium dodecyl sulfate (SDS), a widely used surfactant in detergents, has raised concerns due to its potential health risks, particularly in children. This study evaluates the impact of SDS exposure on GH secretion in GH3 cells, focusing on oxidative stress as a key mechanism.MethodsGH3 cells were treated with varying concentrations of SDS (0.001-10 mM) for 24 or 48 h. Cell viability was assessed using the MTT assay, while GH secretion was quantified via ELISA. Oxidative stress levels were evaluated through ROS fluorescence assays, and gene expression of Nrf2, IL-6, TNF-α, and caspase-3 was analyzed using qPCR. Additionally, the antioxidant N-acetylcysteine (NAC) was used to determine its protective effects against SDS-induced oxidative stress.ResultsSDS exposure led to a dose-dependent decrease in GH secretion and cell viability, with oxidative stress identified as a primary driver. Nrf2 exhibited a biphasic response, showing transient upregulation at low doses but suppression at higher concentrations, exacerbating oxidative damage. NAC treatment reduced ROS levels and partially restored GH secretion, confirming the role of oxidative stress in SDS-induced toxicity.DiscussionThese findings suggest that SDS exposure may disrupt endocrine function, warranting further risk assessment of its safety in consumer products. Given SDS's prevalence in household products, future research should focus on the long-term effects of SDS exposure to children and potential therapeutic interventions to mitigate oxidative damage.

IntroductionThe investigation focused on the function of LINC00958 in the development of oral cancer, as well as the influence of methylation on tumor formation.MethodsTo explore the role of LINC00958, both its overexpression and its methylated form were examined in oral cancer cells. Various assays including CCK-8, transwell, plate cloning, flow cytometry, and EdU staining were utilized to assess the activity, invasion, cloning efficiency, cell cycle progression, and proliferation of the cancer cells. The tumorigenic potential of these cells was evaluated through experiments conducted on immunodeficient mice. Moreover, the methylation status of LINC00958 mediated by the KIAA1429 protein was confirmed using MeRIP-qPCR.ResultsThe study indicated that the overexpression of LINC00958 enhanced the activity, proliferation, and invasive capabilities of oral cancer cells, thereby increasing their tumorigenic potential. In contrast, overexpression of KIAA1429 led to a decrease in the proliferation, invasion, and tumorigenic properties of these cancer cells. Verification of methylation levels indicated that KIAA1429 overexpression resulted in heightened methylation of LINC00958. It was concluded that KIAA1429 diminishes the proliferation, invasion, and tumorigenesis of cancer cells through the methylation of LINC00958.DiscussionThis research provided insights into the role of LINC00958 in oral cancer cells and underscored the impact of methylation, offering a theoretical foundation for improving clinical diagnosis and treatment strategies for oral cancer patients.