Interconnected environmental challenges: heavy metal-drug interactions and their impacts on ecosystems.

Industrial expansion and inadequate environmental safety measures are major contributors to environmental contamination, with heavy metals (HMs) and pharmaceutical waste playing crucial roles. Their negative effects are most noticeable in aquatic species and vegetation, where they accumulate in tissues and cause harmful results. Interactions between HMs and pharmaceutical molecules result in the production of metal-drug complexes (MDCs), which have the potential to disturb diverse ecosystems and their interdependence. However, present studies frequently focus on individual pollutants and their effects on specific environmental parameters, leaving out the cumulative effects of pollutants and their processes across several environmental domains. To address this gap, this review emphasizes the environmental sources of HMs, elucidates their emission pathways during anthropogenic activities, investigates the interactions between HMs and pharmaceutical substances, and defines the mechanisms underlying the formation of MDCs across various ecosystems. Furthermore, this review underscores the simultaneous occurrence of HMs and pharmaceutical waste across diverse ecosystems, including the atmosphere, soil, and water resources, and their incorporation into biotic organisms across trophic levels. It is important to note that these complex compounds represent a higher risk than individual contaminants.

Cadmium and ketoprofen accumulation influences aquatic ecosystem demonstrated using in-vivo zebrafish model.

The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems.

Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish.

Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.

Parental (F0) exposure to Cadmium and Ketoprofen induces developmental deformities in offspring (F1): A transgenerational toxicity assessment in zebrafish model.

In the aquatic environment, the primary pollutants of heavy metals and pharmaceuticals always occur in coexisting forms, and the research about combined impacts remains unclear, especially transgenerational effects. Cadmium (Cd) is a heavy metal that can damage the endocrine reproduction systems and cause thyroid dysfunction in fish. Meanwhile, ketoprofen (KPF) is a nonsteroidal anti-inflammatory drug (NSAID) that can cause neurobehavioral damage and physiological impairment. However, to our knowledge, the combined exposure of Cd and KPF in transgenerational studies has not been reported. In this investigation, sexually mature zebrafish were subjected to isolated exposure and combined exposure to Cd (10 µg/L) and KPF (10 and 100 µg/L) at environmentally relevant concentrations for 42 days. In this background, breeding capacity, chemical accumulation rate in gonads, and tissue morphologies are investigated in parental fish. This is followed by examining the malformation rate, inflammation rate, and gene transcription in the F1 offspring. Our results indicate that combined exposure of Cd and KPF to the parental fish could increase the chemical accumulation rate and tissue damage in the gonads of fish and significantly reduce the breeding ability. Furthermore, these negative impacts were transmitted to its produced F1 embryos, reflected by hatching rate, body deformities, and thyroid axis-related gene transcription. These findings provide further insights into the harm posed by Cd in the presence of KPF to the aquatic ecosystems.

Toxicity and therapeutic property of dioxopiperidin derivative SKT40 demonstrated in-vivo zebrafish model due to inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses chronic disorders that cause severe inflammation in the digestive tract. This study evaluates (E)-3-(3,4-dichlorophenyl)-N-(2,6-dioxopiperidin-3-yl) acrylamide (named SKT40), a derivative of dioxopiperidinamide, as a potential novel treatment for IBD. The pharmacological activity of SKT40 indicated positive interactions using network pharmacology and molecular docking in silico. In vivo, adult and larval zebrafish were tested to evaluate the effectiveness of SKT40 at different concentrations (7.5 µM, 10 µM, 15 µM) in preventing dextran sulfate sodium (DSS)-induced intestinal inflammation. The administration of SKT40 resulted in positive effects by reducing reactive oxygen species (ROS), lipid peroxidation, and cell apoptosis in zebrafish larvae. SKT40 demonstrated a significant reduction in intestinal damage in adult zebrafish by increasing antioxidant enzymes that combat the causes of IBD, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). It also reduces cellular damage and inflammation, as indicated by decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA). Gene expression analysis identified downregulation in gene expression of inflammatory mediators such as TNF-α, IL-1ß, COX-2, and IL-6. Histopathological analysis showed tissue repair from DSS-induced damage and indicated reduced hyperplasia of goblet cells. These findings suggest that SKT40 effectively treats intestinal damage, highlighting its potential as a promising candidate for IBD therapy.

Skeletal and neurological risks demonstrated in zebrafish due to second-hand cigarette smoke and the neutralization of luteolin.

BACKGROUND: Cigarette smoke exposure poses significant health risks, including oxidative stress, inflammation, tissue damage, and neurodegenerative diseases. Luteolin, a natural flavonoid known for its antioxidant and anti-inflammatory properties, is of interest in countering these effects. AIM: This study aims to assess luteolin's protective potential against cigarette smoke extract (CSE) in adult zebrafish. MATERIALS AND METHODS: Adult zebrafish were exposed to CSE for 15 days, inducing smoke-related damage. Subsequent luteolin treatment assessed its impact. Evaluations included antioxidant enzymes (SOD, CAT), nitric oxide (NO), LDH activity (cellular damage), tissue integrity, fibrosis, amyloid plaque accumulation, and CSE component analysis via HPLC. KEY FINDINGS: CSE exposure heightened oxidative stress, reducing SOD and CAT activity and elevating NO levels, leading to cellular damage and tissue disruption, notably fibrosis and amyloid plaque accumulation. Inflammatory markers TNF-α and IL-1ß also increased. Luteolin treatment restored SOD and CAT activity, reduced LDH and NO activity, counteracting oxidative damage. It also mitigated fibrosis and reduced amyloid plaque deposition, preserving tissue integrity. Luteolin reduced TNF-α and IL-1ß levels and CSE components, displaying anti-inflammatory effects. SIGNIFICANCE: This study underscores luteolin's potential as a protective agent against cigarette smoke-induced harm in a zebrafish model.