Search Results (35)

The widespread availability and pseudo-persistence of typical psychiatric pharmaceuticals (PDs) can have serious impacts on aquatic ecosystems and even human health. However, the toxicokinetics of typical PDs and the corresponding enzymatic biomarker responses are unclear. In this study, eight typical PDs [carbamazepine (CBZ), citalopram (CIT), sertraline (SER), venlafaxine (VLF), amitriptyline (AMT), chlorpromazine (CPM), quetiapine (QTP) and clozapine (CLZ)] were selected to study the uptake, depuration and biological effects of PDs in Daphnia magna. The results found that the uptake rates (K_u) were in the sequence of VLF < QTP < CBZ < CLZ < CIT < AMT < SER < CPM, while the depuration rates (K_d) were in the order of CLZ < AMT < CIT < SER < QTP < CBZ < CPM < VLF. Correspondingly, the bioconcentration factors (BCFs) followed on as VLF < QTP < CBZ < CIT < AMT < CLZ < SER < CPM. Both pH-dependent octanol–water partition coefficients (log D_ow) and liposome–water partition coefficients (log D_lip-w) exhibited positive correlations with the log BCF of PDs (p < 0.05), indicating the important roles of ionization degree and biological phospholipid contents on bioconcentration. Superoxide dismutase (SOD) activities were evidently induced in the SER and CPM groups, while ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST) activities were significantly induced only in the CBZ group. Acetylcholinesterase (AChE) activity was obviously induced by CBZ, SER and AMT, with levels 1.73, 1.62 and 2.44 times that of the control group (p < 0.05). The K_u of PDs, oxidative stress and metabolic level of D. magna combine to affect BCF levels together. In conclusion, this study contributes to a better understanding of the toxicokinetics and biochemical responses of PDs in D. magna and potential mechanisms of action, which may allow for a better assessment of their environmental health risks to aquatic ecosystems. Full article

This experimental study evaluated the impacts of three nutraceuticals [liposomal vitamin C, coenzyme Q10 (CoQ10), and bee venom (BV)] on the physiological parameters of Nile tilapia (Oreochromis niloticus). A total of 360 fish (initial weight: 35.17 ± 0.22 g) were randomly allocated to four isonitrogenous and isolipidic dietary treatments: a control group and three supplementation groups (liposomal vitamin C at 200 mg/kg, CoQ10 at 60 mg/kg, and BV at 4 mg/kg), with three replicates per treatment, and fish were fed to apparent satiation. After a 60-day feeding trial, comprehensive analyses revealed significant improvements in growth performance, digestive enzyme activities, immune responses, and antioxidant status across supplemented groups, with bee venom exhibiting the most pronounced effects. Nutraceutical supplementation enhanced gastrointestinal enzyme activities, modulated gut microbiota composition, and improved liver and intestinal histological characteristics. Immunological assessments demonstrated elevated lysozyme levels, bactericidal activity, and respiratory burst activity, while antioxidant markers showed increased superoxide dismutase, catalase, and glutathione peroxidase activities, accompanied by reduced malondialdehyde levels. These findings suggest that strategic nutraceutical supplementation can substantially optimize physiological functions and health parameters in Nile tilapia aquaculture. Full article

Objectives: Resveratrol (RES) is well documented for its multiple health benefits, with a notable impact on cancer prevention and therapy. This study aimed to evaluate the effect of RES supplementation on oxidative stress in patients with head and neck cancer (HNC) receiving home enteral nutrition (HEN). Methods: This randomized, single-center, open-label study involved 72 adult patients, with 40 completing the intervention. Participants in the intervention group received 400 mg of liposomal RES daily for 12 weeks alongside HEN, while the control group received HEN only. Body composition and oxidative stress markers—including total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH)—were measured at baseline and after 12 weeks. Results: Significant increases in TAC and SOD activity were observed in both groups. GPx activity increased significantly only in the RES group. MDA levels rose in both groups but were more pronounced in the RES group. GSH levels showed no significant changes. Phase angle (PhA) increased significantly in the RES group, while no significant change was observed in the control group. Conclusions: RES supplementation may enhance antioxidant defenses, as evidenced by increased GPx activity and improvements in TAC and SOD levels, supporting oxidative balance in patients with HNC receiving HEN. The higher MDA levels in the RES group may reflect RES’s dual antioxidant and pro-oxidant activities. Additionally, the observed increase in PhA suggests potential cellular health benefits. These findings highlight the potential of RES as a complementary antioxidant intervention in clinical oncology, warranting further investigation to clarify its therapeutic effects on oxidative stress and cellular health in cancer care. Full article

Heterogeneous persulfate activation is an advanced technology for treating harmful algae in drinking water sources, while it remains a significant hurdle in the efficient management of cyanobacterial blooms. In this study, super-dispersed cobalt-doped carbon nitride (2CoCN) was prepared to activate peroxymonosulfate (PMS) for simultaneous Microcystis aeruginosa inhibition and microcystin (MC-LR) degradation. When the initial PMS and 2CoCN concentrations were 0.3 g/L and 0.4 g/L, respectively, the efficiency of algal cell removal reached 97% in 15 min, and the degradation of MC-LR reached 96%. Analyses by SEM, TEM, and EEM spectra revealed that the reaction led to changes in algal cell morphology, damage to the cell membrane and cell wall, and the diffusion of thylakoid membranes and liposomes. The activities of antioxidant enzymes (superoxide dismutase and catalase) and antioxidants (glutathione) in algal cells generally increased, and the content of malondialdehyde increased, indicating severe damage to the cell membrane. Radical capture experiments confirmed that singlet oxygen (¹O₂) was the key species destroying algal cells in the 2CoCN/PMS system. The 2CoCN/PMS system was effective in removing M. aeruginosa within a wide pH range (3–9), and 2CoCN had good reusability. Additionally, three degradation products of MC-LR were identified by LC–MS/MS analysis, and a possible mechanism for the inactivation of M. aeruginosa and the degradation of MC-LR was proposed. In conclusion, this study pioneered the 2CoCN/PMS system for inhibiting M. aeruginosa and degrading microcystin, aiming to advance water purification and algae removal technology. Full article

Protium heptaphyllum (P. heptaphyllum), popularly known as “almacega” or “white pitch”, is widely used in folk medicine due to its antioxidant, anti-inflammatory and healing properties, attributed to its richness in flavonoids and terpenes. Therefore, this study aimed to evaluate the effects of treatment for 28 days with liposomes containing P. heptaphyllum leaf extract in obese animals. Male Wistar rats, subjected to a hypercaloric diet for 8 weeks to induce obesity (hypercaloric chow and water enriched with 30% sucrose, ad libitum), were treated with the plant formulation (1 mg kg⁻¹day⁻¹, via gavage) for 28 days. The study investigated morphological, metabolic, redox state, immunological and histological parameters in adipose and liver tissue. Rats were divided into four groups: control (C), liposomes with extract (H), obese (O) and obese treated with liposomes containing extract (OH). The results indicated that the obese group (O) presented weight gain, hepatic steatosis and alterations in metabolic and inflammatory parameters. However, treatment with liposomes (OH) reduced glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine and the lipid profile. In adipose tissue, the OH group showed decreased superoxide dismutase (SOD) activity and increased glutathione S-transferase (GST) activity, in contrast to the effects observed in liver GST. In the analysis of thiobarbituric-acid-reactive substances (TBARS), it was possible to observe an increase in all groups in adipose tissue and in group O in liver tissue, in addition to a reduction in TBARS in group OH in the liver, indicating modulation of oxidative stress. The treatment also increased the concentration of IL-10 and IL-17 in the liver and decreased that of IL-6 in adipose tissue. After 28 days of treatment, these results point to the therapeutic potential of treatment with P. heptaphyllum, not necessarily only against obesity, but also an effect per se of the liposomes, possibly due to the high concentration of flavonoids present in the plant extract. Full article

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage) and 100 mg/kg of CPA in a single dose (via intraperitoneal) on the 15th day. After the experimental period, blood and organ samples were collected for histopathological and biochemical analyses, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), ascorbic acid (ASA), carbonyl protein, cytokine measurement, and micronucleus testing. The results showed that liposomes containing P. heptaphyllum extract have an antimutagenic effect against damage induced to DNA by CPA, and that they also protect against oxidative stress, as verified by the increase in the antioxidant enzymes SOD and GPx. The improvement in alkaline phosphatase and creatinine markers suggests a beneficial effect on the liver and kidneys, respectively. However, the depletion of GSH in the liver and brain suggests the use of antioxidants for the metabolism of molecules generated in these tissues. In general, these data show good prospects for the use of P. heptaphyllum liposomes as a cancer chemoprotective agent, as well as possible antioxidant action, conceivably attributed to the flavonoids present in the plant extract. Full article

Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections. Full article

The inhibition of the immune response in the tumor microenvironment by therapy regimens can impede the eradication of tumors, potentially resulting in tumor metastasis. As a non-invasive therapeutic method, radiotherapy is utilized for tumor ablation. In this study, we aimed to improve the therapeutic impact of radiotherapy and trigger an immune response by formulating a benzothiazole sulfinate (BTS)-loaded fusion liposome (BFL) nanoplatform, which was then combined with radiotherapy for anti-cancer treatment. The platelet cell membrane, equipped with distinctive surface receptors, enables BFL to effectively target tumors while evading the immune system and adhering to tumor cells. This facilitates BFL’s engulfment by cancer cells, subsequently releasing BTS within them. Following the release, the BTS produces sulfur dioxide (SO₂) for gas therapy, initiating the oxidation of intracellular glutathione (GSH). This process demonstrates efficacy in repairing damage post-radiotherapy, thereby achieving effective radiosensitization. It was revealed that an immune response was triggered following the enhanced radiosensitization facilitated by BFL. This approach facilitated the maturation of dendritic cell (DC) within lymph nodes, leading to an increase in the proportion of T cells in distant tumors. This resulted in significant eradication of primary tumors and inhibition of growth in distant tumors. In summary, the integration of personalized BFL with radiotherapy shows potential in enhancing both tumor immune response and the elimination of tumors, including metastasis. Full article

In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes were characterized for size, surface charge and drug encapsulation efficiency before and after coating. The formation of a coating layer on liposomal surface was confirmed by the slight increase in particle size and by zeta-potential changes. FTC-coated liposomes showed a redox-dependent drug release profile: good stability at physiological conditions and rapid release of liposome-entrapped calcein in presence of glutathione. Moreover, the uptake and cytotoxic activity of doxorubicin-loaded FTC-coated liposomes was evaluated on murine B16-F10 and human SKMEL2 melanoma cancer cells. Results demonstrated enhanced uptake and antitumor efficacy of FTC-coated liposomes compared to control chitosan-coated liposomes in both cancer lines, which is attributed to higher cellular uptake via folate receptor-mediated endocytosis and to triggered drug release by the reductive microenvironment of tumor cells. The proposed novel liposomes show great potential as nanocarriers for targeted therapy of cancer. Full article

Thrombotic microangiopathy has been identified as a dominant mechanism for increased mortality and morbidity in coronavirus disease 2019 (COVID-19). In the context of severe COVID-19, patients may develop immunothrombosis within the microvasculature of the lungs, which contributes to the development of acute respiratory distress syndrome (ARDS), a leading cause of death in the disease. Immunothrombosis is thought to be mediated in part by increased levels of cytokines, fibrin clot formation, and oxidative stress. Glutathione (GSH), a well-known antioxidant molecule, may have therapeutic effects in countering this pathway of immunothrombosis as decreased levels of (GSH) have been associated with increased viral replication, cytokine levels, and thrombosis, suggesting that glutathione supplementation may be therapeutic for COVID-19. GSH supplementation has never been explored as a means of treating COVID-19. This study investigated the effectiveness of liposomal glutathione (GSH) as an adjunctive therapy for peripheral blood mononuclear cells (PBMC) treated with SARS CoV-2 spike protein. Upon the addition of GSH to cell cultures, cytokine levels, fibrin clot formation, oxidative stress, and intracellular GSH levels were measured. The addition of liposomal-GSH to PBMCs caused a statistically significant decrease in cytokine levels, fibrin clot formation, and oxidative stress. The addition of L-GSH to spike protein and untreated PBMCs increased total intracellular GSH, decreased IL-6, TGF-beta, and TNF-alpha levels, decreased oxidative stress, as demonstrated through MDA, and decreased fibrin clot formation, as detected by fluorescence microscopy. These findings demonstrate that L-GSH supplementation within a spike protein-treated PBMC cell culture model reduces these factors, suggesting that GSH supplementation should be explored as a means of reducing mediators of immunothrombosis in COVID-19. Full article

Antioxidants, usually administered orally through the systemic route, are known to counteract the harmful effects of oxidative stress on retinal cells. The formulation of these antioxidants as eye drops might offer a new option in the treatment of oxidative retinopathies. In this review, we will focus on the use of some of the most potent antioxidants in treating retinal neuropathies. Melatonin, known for its neuroprotective qualities, may mitigate oxidative damage in the retina. N-acetyl-cysteine (NAC), a precursor to glutathione, enhances the endogenous antioxidant defense system, potentially reducing retinal oxidative stress. Idebenone, a synthetic analogue of coenzyme Q10, and edaravone, a free radical scavenger, contribute to cellular protection against oxidative injury. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, possesses anti-inflammatory and antioxidant effects that could be beneficial in cases of retinopathy. Formulating these antioxidants as eye drops presents a localized and targeted delivery method, ensuring effective concentrations reach the retina. This approach might minimize systemic side effects and enhance therapeutic efficacy. In this paper, we also introduce a relatively new strategy: the alkylation of two antioxidants, namely, edaravone and EGCG, to improve their insertion into the lipid bilayer of liposomes or even directly into cellular membranes, facilitating their crossing of epithelial barriers and targeting the posterior segment of the eye. The synergistic action of these antioxidants may offer a multifaceted defense against oxidative damage, holding potential for the treatment and management of oxidative retinopathies. Further research and clinical trials will be necessary to validate the safety and efficacy of these formulations, but the prospect of antioxidant-based eye drops represents a promising avenue for future ocular therapies. Full article

We previously reported that maternal alcohol use increased the risk of sepsis in premature and term newborns. In the neonatal mouse, fetal ethanol (ETOH) exposure depleted the antioxidant glutathione (GSH), which promoted alveolar macrophage (AM) immunosuppression and respiratory syncytial virus (RSV) infections. In this study, we explored if oral liposomal GSH (LGSH) would attenuate oxidant stress and RSV infections in the ETOH-exposed mouse pups. C57BL/6 female mice were pair-fed a liquid diet with 25% of calories from ethanol or maltose–dextrin. Postnatal day 10 pups were randomized to intranasal saline, LGSH, and RSV. After 48 h, we assessed oxidant stress, AM immunosuppression, pulmonary RSV burden, and acute lung injury. Fetal ETOH exposure increased oxidant stress threefold, lung RSV burden twofold and acute lung injury threefold. AMs were immunosuppressed with decreased RSV clearance. However, LGSH treatments of the ETOH group normalized oxidant stress, AM immune phenotype, the RSV burden, and acute lung injury. These studies suggest that the oxidant stress caused by fetal ETOH exposure impaired AM clearance of infectious agents, thereby increasing the viral infection and acute lung injury. LGSH treatments reversed the oxidative stress and restored AM immune functions, which decreased the RSV infection and subsequent acute lung injury. Full article

Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results. Full article

In the present study, the effects of Origanum onites L. extract and essential oil of O. onites L. on the antioxidant status of the liver and brain of mice were investigated. Due to certain disadvantages of essential oils, such as poor solubility, high volatility and sensitivity to UV light and heat, formulation of liposomes with Oregano essentials (OE) was optimized and used in this study. The results demonstrated that the best composition of the lipid carriers and OE were conducted in terms of the polydispersity index (PDI), mean particle size and encapsulation efficiency (EE). For further study the LE4 formulation was used, which contained Lipoid S100 at 45 mg, Lipoid S75 at 45 mg and 90 mg of EO. The administration of O. onites L. extract to mice for 21 days significantly decreased the glutathione (GSH) level in the livers and brains of the mice as well as the malondialdehyde (MDA) concentration in the livers. In the brains of the mice, MDA level significantly increased after this extract consumption. Whereas liposomes with OE significantly decreased GSH concentration in the mouse brain and MDA concentration in the mouse liver, there was an increased (p > 0.05) GSH level in the liver and MDA concentration in the brain of mice compared with the control group. It was found that both O. onites. ethanolic extract as well as liposomes with OE of this plant material affect the antioxidant status in the livers and brains of mice. Full article

Glutathione (GSH) is an important intracellular antioxidant responsible for neutralizing reactive oxygen species (ROS). Our laboratory previously demonstrated that the oral administration of liposomal GSH improves immune function against mycobacterium infections in healthy patients along with patients with HIV and Type 2 diabetes. We aim to determine if the topical application of a glutathione–cyclodextrin nanoparticle complex (GSH-CD) confers a therapeutic effect against mycobacterium infections. In our study, healthy participants received either topical GSH-CD (n = 15) or placebo (n = 15) treatment. Subjects were sprayed four times twice a day for three days topically on the abdomen. Blood draws were collected prior to application, and at 1, 4, and 72 h post-initial topical application. GSH, malondialdehyde (MDA), and cytokine levels were assessed in the processed blood samples of study participants. Additionally, whole blood cultures from study participants were challenged with Mycobacterium avium (M. avium) infection in vitro to assess mycobacterium survival post-treatment. Topical GSH-CD treatment was observed to elevate GSH levels in peripheral blood mononuclear cells (PBMCs) and red blood cells and decrease MDA levels in PBMCs 72 h post-treatment. An increase in plasma IL-2, IFN-γ, IL-12p70, and TNF-α was observed at 72 h post-topical GSH-CD treatment. Enhanced mycobacterium clearance was observed at 4 h and 72 h post-topical GSH-CD treatment. Overall, topical GSH-CD treatment was associated with improved immune function against M. avium infection. The findings of this pilot study suggest GSH–cyclodextrin complex formulation can be used topically as a safe alternative mode of GSH delivery in the peripheral blood. Full article