Atrazine (ATR), a widely used herbicide, poses significant environmental and health risks due to its high solubility and adsorption in soil. ATR exposure can lead to nephrotoxicity in humans and animals. Curcumin (Cur), an active compound in Curcuma species, is renowned for its antioxidant and anti-inflammatory properties, with potential to mitigate chronic disease risks. We hypothesized that the addition of Cur could alleviate renal impairment associated with ATR exposure and carried out experiments using mice as subjects. This study investigates whether Cur can attenuate ATR-induced nephrotoxicity in mice by modulating mitophagy and apoptotic pathways. Our findings illustrate that consumption with Cur attenuates nephrotoxicity induced by ATR, as evidenced by lowered serum concentrations of uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE), established biomarkers of renal injury. Moreover, Curcumin enhances renal antioxidant defense mechanisms in ATR-exposed mice, as indicated by elevated levels of total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-Px), alongside reduced levels of malondialdehyde (MDA). Histopathological and electron microscopy analyses further corroborate these findings, showing reduced organelle damage, particularly mitochondrial ridge breakage and vacuolization, and increased autophagic lysosomes. Cur further enhances PINK1/Parkin-mediated autophagy, as evidenced by elevated levels of PINK1, Parkin, LC3BII, and P62 compared to ATR-treated mice. Moreover, Cur mitigates the mitochondrial apoptotic pathway, indicated by the down-regulation of apoptosis-related genes (Cytochrome C (Cyto-C), Caspase3, Caspase9) and the proapoptotic marker (Bax), along with the up-regulation of the anti-apoptotic marker (Bcl-2) at both transcriptional and translational levels compared to ATR-treated mice. In summary, Cur demonstrates nephroprotective properties against ATR-induced injury through the enhancement of mitochondrial autophagy and display of antiapoptotic actions, underscoring its curative potency as a treatment for nephrotoxicity caused by ATR.
Micro/Nano plastics (MNPs) pollutants are widespread in the environment, raising significant concerns about their biosafety. Emerging studies indicate that the urinary system is a primary accumulation site for MNPs, leading to severe tissue and functional damage. This review aims to summarize recent research on the potential hazards that MNPs may pose to the urinary system, highlighting the mechanisms of toxicity and the current state of knowledge. Studies have shown that MNPs enter the human body through drinking water, the food chain, inhalation, and skin contact. They may penetrate the bloodstream via the digestive, respiratory, and skin systems, subsequently dispersing to various organs, including the urinary system. The potential accumulation of MNPs in the urinary system might induce cellular oxidative stress, inflammation, apoptosis, autophagy, the intestine-kidney axis, and other possible toxic mechanisms. These processes could disrupt kidney metabolic functions and promote tissue fibrosis, thereby potentially increasing the risk of urinary system diseases. Despite ongoing research, the understanding of MNPs' impact on the urinary system remains limited. Therefore, this review provides a comprehensive overview of MNPs' potential toxicity mechanisms in the urinary system, highlights key challenges, and outlines future research directions. It offers a theoretical basis for the development of effective protective measures and policies.
In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 mu M to 10 mu M) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.
BACKGROUND: Spodoptera litura is one of the most harmful lepidoptera pests in China, and is difficult to control due to its strong resistance to the current frequently used insecticide species. The requirement to develop pesticides with novel toxicology mechanisms to control S. litura is urgent. The quassinoid of bruceine D display outstanding systemic properties and strong insecticidal activity against S. litura, which possess notable application potential for integrative management of S. litura, but the mechanism of toxicity remains unclear. RESULTS: In this study, we found that bruceine D exerts potent growth inhibitory activity against S. litura, disrupting the ecdysone and juvenile hormone titers, and causing long-term adverse effects. Association analysis between transcriptomics and metabolomics suggested that bruceine D affected the digestion and absorption capacity of S. litura larvae by inducing a strong oxidative stress response and cell apoptosis in the intestine. Further analysis demonstrated that bruceine D can inhibit the activities of digestive and antioxidant enzymes and induce malondialdehyde (MDA) and reactive oxygen species (ROS) overaccumulation in the midgut. Moreover, the protein level of Bax, cleavage caspase 3, and cytochrome c expressed in cytoplasm (cyto) were up-regulated by bruceine D, while Bcl-2 and cytochrome c expressed in mitochondria (mito) were down-regulated. In addition, there was a noticeable increase in caspase-3 protease activity. Histopathological observations revealed that bruceine D damages the structure of midgut epithelial cells and activates lysosomes, which subsequently disrupts the midgut tissue. CONCLUSION: Overall, our findings suggested that bruceine D induced excessive ROS accumulation in midgut epithelial cells. The resulting cell apoptosis disrupted midgut tissue, leading ultimately to reduced nutrient digestion and absorption in the midgut and the inhibition of larval growth. (c) 2024 Society of Chemical Industry.
Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosislike cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress.
Fusarium wilt is a worldwide soil-borne fungal disease caused by Fusarium oxysporum that causes serious damage to agricultural products. Therefore, preventing and treating fusarium wilt is of great significance. In this study, we purified ten single lipopeptide fengycin components from Bacillus subtilis FAJT-4 and found that C-17 fengycin B inhibited the growth of F. oxysporum FJAT-31362. We observed early apoptosis hallmarks, including reactive oxygen species accumulation, mitochondrial dysfunction, and phosphatidylserine externalization in C-17 fengycin B-treated F. oxysporum cells. Further data showed that C-17 fengycin B induces cell apoptosis in a metacaspase-dependent manner. Importantly, we found that the expression of autophagy-related genes in the TOR signaling pathway was significantly upregulated; simultaneously, the accumulation of acidic autophagy vacuoles in F. oxysporum cell indicated that the autophagy pathway was activated during apoptosis induced by C-17 fengycin B. Therefore, this study provides new insights into the antifungal mechanism of fengycin.
Breast cancer is one of the most common and deadly cancers in women worldwide. Current treatments for breast cancer have limitations, such as toxicity, resistance, and side effects. Therefore, there is a need to develop new and effective anti-cancer agents from natural sources. Spinosyn A (SPA) is a natural product derived from soil bacteria. SPA has been reported to have anti-parasitic, insecticidal, and anti-bacterial activities. However, its anti-cancer effects and mechanisms are not well understood. In this study, we investigated the effects of SPA on T47-D, estrogen receptor-positive breast cancer cells. We found that SPA inhibited cell proliferation and migration and induced apoptosis and cell cycle arrest. Flow cytometry and holographic imaging microscopy revealed that SPA activated MAPK and PI3K signaling pathways and altered cellular morphology. Finally, RNASeq analysis revealed that SPA treatment altered the expression of 1380 genes in T47-D cells, which were enriched in various biological processes and signaling pathways related to cell proliferation, cholesterol metabolism, growth factor activity, amino acid transport activity, extracellular matrix, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and PPAR signaling pathway. Our results suggest that SPA exerts multiple anti-cancer effects on T47-D cells by modulating multiple pathways and cellular processes involved in cell growth, survival, and motility. Our findings provide new insights into the molecular mechanisms of SPA action on breast cancer cells and its potential applications as a novel anti-cancer agent.
Gibberellic acid (GA3), one of the most plant growth stimulator, is widely applied in agricultural regions and in beer industry. However, GA3 residue remained in soil and water can cause toxicity to all organisms. In this study, we investigated the mechanisms of GA3-induced hepatic injury in gibel carp (Carassius auratus gibelio). We found that GA3 exposure caused oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. The gibel carp exposed to GA3 exhibited significant alteration in erythrocyte nuclei. GA3 induced liver damage, as indicated by increasing the aminopherase activities. GA3 led to oxidative stress by increasing malondialdehyde content and decreasing the activities of CAT and GPx. GA3 stimulated ERS and increased the expression of grp78, perk, eif2s1 alpha, chop, atf4, ire1 alpha, xbp1, and atf6. Additionally, GA3 down-regulated the level of anti-apoptotic gene Bcl2 and up-regulated the levels of pro-apoptotic genes bax and caspase-3. Overall results demonstrated that GA3 caused hepatic injury in gibel carp by increasing oxidative stress, ERS, and apoptosis.
Atrazine (ATR), a water-soluble herbicide commonly used to control broad-leaf and monocotyledonous weeds, presents a significant risk to environmental soil and water quality. Exposure to ATR adversely affects human and animal health, frequently resulting in cardiac impairment. Curcumin (Cur), an acidic polyphenol derivative from plants acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. However, whether it has the potential to ameliorate ATR-induced cardiac toxicity via modulation of endoplasmic reticulum stress (ERS) and apoptosis pathways in mice remains unclear. Our results showed that Cur supplementation attenuates ATR-induced cardiotoxicity, evidenced by decrease in creatine kinase and lactate dehydrogenase, key biochemical markers of myocardial injury, which have a more significant protecting effect in high-dose ATR induced injury. Histopathological and electron microscopy examinations further solidified these findings, demonstrating an amelioration in organellar damage, particularly in endoplasmic reticulum swelling and subsequent mitochondrial impairment. Additionally, ATR exposure augments ERS and triggers apoptotic pathways, as indicated by the upregulation of ERS-related gene expression (ATF6, CHOP, IRE1, GRP78) and pro-apoptotic markers (BAX, BAK1, Caspase3, Caspase. Intriguingly, Cur counteracts this detrimental response, significantly reducing ERS and pro-apoptotic signals at both transcriptional and translational levels. Collectively, our findings illuminate Cur's cardioprotective effect against ATRinduced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring Cur's potential as a therapeutic for ATR-induced cardiotoxicity.
Cadmium (Cd) is a malleable element with odorless, tasteless characteristics that occurs naturally in the earth's crust, underground water, and soil. The most common reasons for the anthropological release of Cd to the environment include industrial metal mining, smelting, battery manufacturing, fertilizer production, and cigarette smoking. Cadmium-containing products may enter the environment as soluble salts, vapor, or particle forms that accumulate in food, soil, water, and air. Several epidemiological studies have highlighted the association between Cd exposure and adverse health outcomes, especially renal toxicity, and the impact of Cd exposure on the development and progression of carcinogenesis. Also highlighted is the evidence for early-life and even maternal exposure to Cd leading to devastating health outcomes, especially the risk of cancer development in adulthood. Several mechanisms have been proposed to explain how Cd mediates carcinogenic transformation, including epigenetic alteration, DNA methylation, histone posttranslational modification, dysregulated noncoding RNA, DNA damage in the form of DNA mutation, strand breaks, and chromosomal abnormalities with double-strand break representing the most common DNA form of damage. Cd induces an indirect genotoxic effect by reducing p53 ' s DNA binding activity, eventually impairing DNA repair, inducing downregulation in the expression of DNA repair genes, which might result in carcinogenic transformation, enhancing lipid peroxidation or evasion of antioxidant interference such as catalase, superoxide dismutase, and glutathione. Moreover, Cd mediates apoptosis evasion, autophagy activation, and survival mechanisms. In this review, we decipher the role of Cd mediating carcinogenic transformation in different models and highlight the interaction between various mechanisms. We also discuss diagnostic markers, therapeutic interventions, and future perspectives.