Astaxanthin alleviates PM2.5-induced cardiomyocyte injury via inhibiting ferroptosis.

BACKGROUND: Long-term exposure of humans to air pollution is associated with an increasing risk of cardiovascular diseases (CVDs). Astaxanthin (AST), a naturally occurring red carotenoid pigment, was proved to have multiple health benefits. However, whether or not AST also exerts a protective effect on fine particulate matter (PM2.5)-induced cardiomyocyte damage and its underlying mechanisms remain unclear. METHODS: In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined. RESULTS: AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo. CONCLUSIONS: Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.

Flaxseed Oil Alleviates PFOS-Induced Liver Injury by Regulating Hepatic Cholesterol Metabolism.

Perfluorooctanesulfonate (PFOS) is a widespread, persistent environmental pollutant that exerts apparent liver toxicity. Flaxseed oil (FO), a dietary oil rich in α-linolenic acid, has been demonstrated to possess a diverse array of health benefits. However, whether FO protects against PFOS-induced liver injury and its underlying mechanisms remain unclear. C57/BL6 mice were orally treated with different concentrations of FO alone or in combination with 10 mg/kg of PFOS for 28 consecutive days. Blood and liver tissues were collected for proteomic, histopathological, biochemical, immunohistochemical, and molecular examinations. Results demonstrated that FO supplementation reduced PFOS-induced liver injury, as evidenced by a decrease in histopathological changes, serum transaminase (ALT and AST) levels, levels of oxidative stress, and inflammatory cytokine (TNF-α, IL-1ß, and IL-6) levels. Proteomic analyses showed that differentially expressed proteins were enriched in cholesterol metabolic pathways when comparing the PFOS group to the FO supplementation groups. The expression of cholesterol metabolism-related proteins was also subsequently measured, revealing that FO supplementation decreased the protein expressions of SREBP2, HMGCR, and LDLR while increasing the expression of CYP7A1. This study demonstrates that FO can alleviate PFOS-induced hepatotoxicity by regulating hepatic cholesterol metabolism, indicating that FO may serve as an effective dietary intervention for preventing liver injury caused by PFOS.

Flaxseed oil attenuates PFOS-induced testicular damage by regulating RNA alternative splicing.

Background: Perfluorooctane sulfonate (PFOS) is a persistent, widely present environmental pollutant, and its toxicity to male reproduction has gradually attracted attention. Flaxseed oil (FO) is a dietary oil abundant in α-linolenic acid and has been demonstrated to possess multiple health benefits. However, whether FO protects against PFOS-induced testicular injury and its mechanism remain unclear. Methods: C57/BL6 mice were gavaged with different concentrations of FO or PFOS (10 mg kg-1) for 28 days. Blood and testicular tissues were collected for histopathology, proteomics, and biochemical and molecular analyses. Results: Our results showed that FO supplementation significantly attenuated PFOS-induced testicular injury, as indicated by histopathological changes, decreased oxidative stress level, increased sperm count, decreased rate of sperm malformation, and improved functional markers of spermatogenesis. Proteomic analysis showed that differentially expressed proteins were notably enriched in spliceosome pathways. Machine learning algorithms were used to screen the hub gene, and PRPF3 and PUF60 proteins were found to be important for FO to exert protective benefits to testicular injury. Western blot results confirmed that FO supplementation could increase the protein expression of PRPF3 and decrease the protein expression of PUF60 in PFOS-exposed mice. Conclusions: This study revealed that FO can alleviate PFOS-induced testicular dysfunction by regulating RNA alternative splicing. The spliceosome-related proteins PRPF3 and PUF60 may be the potential targets for FO to alleviate PFOS-induced testicular injury. FO supplementation may be an effective dietary intervention to prevent adverse effects of PFOS on testes.

Effects of Sesamin in Animal Models of Obesity-Associated Diseases: A Systematic Review and Meta-Analysis.

CONTEXT: As living standards have improved and lifestyles have undergone changes, metabolic diseases associated with obesity have become increasingly prevalent. It is well established that sesamin (Ses) (PubChem CID: 72307), the primary lignans in sesame seeds and sesame oil, possess antioxidant and anti-inflammatory effects. OBJECTIVE: In this study, a systematic review and meta-analysis of the effects of Ses on animal models of obesity-related diseases was performed to assess their impact on relevant disease parameters. Importantly, this study sought to provide insights for the design of future human clinical studies utilizing Ses as a nutritional supplement or drug. DATA SOURCES: This study conducted a comprehensive search in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library, identifying English language articles published from inception to April 2023. DATA EXTRACTION: The search incorporated keywords such as "sesamin," "obesity," "non-alcoholic fatty liver disease," "type 2 diabetes mellitus," and "metabolic syndrome." The meta-analysis included 17 articles on non-alcoholic fatty liver disease, type 2 diabetes, and metabolic syndrome. DATA ANALYSIS: Overall, the pooled results demonstrated that Ses significantly reduced levels of total serum cholesterol (P = .010), total serum triglycerides (P = .003), alanine transaminase (P = .003), and blood glucose (P < .001), and increased high-density lipoprotein cholesterol levels (P = .012) in animal models of nonalcoholic fatty liver disease. In the type 2 diabetes model, Ses mitigated drug-induced weight loss (P < .001), high-fat-diet-induced weight gain (P < .001), and blood glucose levels (P = .001). In the metabolic syndrome model, Ses was associated with a significant reduction in body weight (P < .001), total serum cholesterol (P < .001), total serum triglycerides (P < .001), blood glucose (P < .001), and alanine transaminase levels (P = .039). CONCLUSION: The meta-analysis results of this study suggest that Ses supplementation yields favorable effects in animal models of obesity-related diseases, including hypolipidemic, insulin-lowering, and hypoglycemic abilities, as well as organ protection from oxidative stress and reduced inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42023438502.

Exposure to volatile organic compounds and growth indicators in adolescents: Unveiling the association and potential intervention strategies.

Environmental pollutant is considered to be one of the important factors affecting adolescent growth. However, the effects of volatile organic compounds (VOCs) exposure on adolescent growth have not been assessed. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 was used to examine the associations between VOCs exposure and adolescent growth indicators through three statistical models. The mediating effect of bone mineral density (BMD) on these associations was examined. The potential pathways and key targets were identified by the network pharmacology analysis methods. This study included 746 adolescents. Three statistical methods consistently showed a negative correlation between VOCs exposure and adolescent growth indicators. Furthermore, BMD mediated the relationship between VOCs exposure and adolescent growth indicators, with mediated proportion ranging from 4.3 % to 53.4 %. Network pharmacology analysis found a significant enrichment in IL-17 signaling pathway. Moreover, the adverse effects of VOCs exposure on adolescent growth were observed to significantly attenuate in adolescents with high serum vitamin D levels. Our results suggested that VOCs exposure was an adverse factor affecting adolescent growth, with BMD playing a significant regulatory role, and IL-17 signaling pathway was the underlying mechanism. Vitamin D supplementation may be a viable strategy to prevent VOCs exposure from affecting adolescent growth.

Astaxanthin alleviates fine particulate matter (PM2.5)-induced lung injury in rats by suppressing ferroptosis and apoptosis.

Objectives: Fine particulate matter (PM2.5), a small molecule particulate pollutant, can reach the lungs via respiration and cause lung damage. Currently, effective strategies and measures are lacking to prevent and treat the pulmonary toxicity of PM2.5. Astaxanthin (ASX), a natural xanthophyll carotenoid, has attracted attention due to its unique biological activity. Our research aims to probe into the prevention and treatment of ASX on PM2.5-induced lung injury and clarify its potential mechanism. Methods: Sprague-Dawley (SD) rats were given olive oil and different concentrations of ASX orally daily for 21 days. PM2.5 suspension was instilled into the trachea of rats every two days for one week to successfully develop the PM2.5 exposure model in the PM2.5-exposed and ASX-treated groups of rats. The bronchoalveolar lavage fluid (BALF) was collected, and the content of lung injury-related markers was detected. Histomorphological changes and expression of markers associated with oxidative stress, inflammation, iron death, and apoptosis were detected in lung tissue. Results: PM2.5 exposure can cause changes in lung histochemistry and increase the expression levels of TP, AKP, ALB, and LDH in the BALF. Simultaneously, inflammatory responses and oxidative stress were promoted in rat lung tissue after exposure to particulate matter. Additionally, ASX preconditioning can alleviate histomorphological changes, oxidative stress, and inflammation caused by PM2.5 and reduce PM2.5-related ferroptosis and apoptosis. Conclusion: ASX preconditioning can alleviate lung injury after PM2.5 exposure by inhibiting ferroptosis and apoptosis.