Aquatic ecosystems are increasingly threatened by multiple anthropogenic stressors, notably climate change and pollution by pharmaceuticals. Global warming is predicted to raise water temperatures by 2–5 °C by the end of the century. As ectotherms, fish are particularly vulnerable due to limited thermal tolerance and temperature-dependent physiology. Pharmaceuticals are introduced into aquatic systems at concentrations ranging from ng·L⁻¹ to µg·L⁻¹, including widely prescribed classes such as antibiotics, hormones, analgesics, antifungals, and neuropsychiatric drugs. This narrative review synthesizes experimental evidence on the interactive effects of warming and pharmaceutical exposure in fish. Thirty-nine peer-reviewed studies published since 2005 were analyzed. The findings indicate that higher temperatures often exacerbate pharmaceutical-induced toxicity, altering oxidative stress, metabolism, reproduction, and behavior. Antibiotic-focused studies showed temperature-dependent acceleration of absorption, distribution, metabolism, and excretion, with shorter half-lives and reduced tissue persistence at higher temperatures. Estrogenic hormones and antifungals have been shown to interact with thermal regimes, disrupting reproductive physiology and skewing sex ratios, particularly in species exhibiting temperature-dependent sex determination. Neuropsychiatric drugs exhibited altered uptake and metabolism under warming conditions, resulting in increased brain bioaccumulation and behavioral alterations affecting ecological fitness. Analgesics and anti-inflammatories remain understudied despite their widespread use, with evidence suggesting synergistic effects on oxidative stress at elevated temperatures. Significant research gaps persist regarding chronic exposures, early developmental stages, ecologically relevant temperature scenarios, and underrepresented or absent drug classes, such as hypolipidemic drugs. Ultimately, broader and integrated approaches are needed to better understand and predict the ecological risks of pharmaceutical pollution in a warming world.

The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)—a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 μL/g for two weeks under the following experimental conditions: control—C (0.7% NaCl), solvent control—SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 μg/g), EE2 (2 μg/g), and a mixture of both compounds—MIX (0.3 μg/g ATV and 2 μg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and β-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (pparγ) and acetyl Co-A oxidase 3 (acox3). EE2 upregulated acyl-CoA long-chain synthetase 1 (acsl1) and downregulated both fatty acid binding protein 1 (fabp1) and acetyl Co-A oxidase 1-3I (acox1-3I). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models.

The brown trout (Salmo trutta) is a commercially and ecologically significant salmonid fish, yet its hepatic cellular and functional dynamics throughout the reproductive cycle remain poorly characterised, particularly in males. This study investigated seasonal and sex-specific liver plasticity across four reproductive stages: spawning capable (December), regressing (March), regenerating (July), and developing (November). We quantified mRNA and protein abundance of key oestrogen-responsive targets—vitellogenin (VtgA) and zona pellucida (ZP) proteins—alongside cell turnover markers, caspase 3 (Casp3) and proliferating cell nuclear antigen (PCNA). These molecular endpoints were integrated with stereological analyses to estimate hepatocyte, nuclear, and cytoplasmic volumes. Results revealed stage-dependent mobilisation and transient hepatic retention of reproductive proteins; females exhibited stronger vitellogenic signatures and more pronounced seasonal shifts than males. Although VtgA and ZP mRNA levels peaked during the developing and spawning-capable stages, males maintained low but consistent levels throughout the cycle, indicating constitutive hepatic oestrogen sensitivity. Regarding cell turnover, PCNA protein data indicated heightened proliferative activity during the spawning-capable and regressing stages. In contrast, while Casp3 mRNA levels remained stable across all stages, protein detection suggested a post-transcriptional increase in apoptotic signalling during the developing phase, consistent with controlled tissue remodelling rather than extensive cell loss. Stereological data confirmed enlarged hepatocyte and nuclear volumes during periods of high secretory and proliferative demand. Overall, these findings demonstrate significant stage-dependent and sex-specific plasticity in brown trout liver, providing a robust reference framework for ecological monitoring, endocrine disruption assessments, and studies of teleost reproductive physiology.

Introduction: Fish and humans share evolutionarily conserved pathways regulating lipid metabolism. However, the effects of pharmaceuticals on lipid homeostasis in fish remain poorly understood, particularly regarding mechanistic lipid dysregulation and its implications for fish physiology and environmental toxicology. While hypolipidemic drugs such as statins have been shown to modulate lipid metabolism in teleosts, other lipid-lowering agents, including cholesterol absorption inhibitors, remain largely unexplored. Additionally, synthetic hormones have been shown to interfere with lipid regulation, although their effects—particularly those of progestins—remain poorly characterized. Objective: This study aimed to explore the mechanistic lipid disruptions induced by potential hypo- and hyperlipidemic modulating pharmaceuticals in brown trout juveniles exposed to subchronic pharmacological conditions. Methodology: Juvenile brown trout were exposed via intramuscular injection every 72 h for 28 days and allocated into six experimental groups (n = 12 per group): control (C; 0.7% NaCl), solvent control (SC; 0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), atorvastatin (ATV; 0.3 µg·g⁻¹), ezetimibe (EZB; 0.3 µg·g⁻¹), 17α-ethinylestradiol (EE2; 2 µg·g⁻¹), and levonorgestrel (LNG; 0.1 µg·g⁻¹). All concentrations represented pharmacological doses. On day 28, the fish were euthanized and sampled. Endpoints included biometric measurements, blood lipid profiling, serum biochemistry, and hepatic lipid accumulation. Results: ATV fish displayed greater body length, whereas EE2 increased liver weight and hepatosomatic index. EE2 reduced high-density lipoproteins and increased low-density lipoproteins, while atorvastatin reduced low-density lipoproteins. EE2 exposure also increased albumin levels and decreased glucose concentrations. Furthermore, EE2 significantly enhanced hepatic lipid deposition. Conclusions: The hyperlipidemic effects of EE2 were the most pronounced, whereas ATV produced the strongest hypolipidemic responses, consistent with its known effects in humans, and also influenced biometry. These findings provide a robust foundation for understanding how pharmaceuticals influence lipid metabolism and related physiological processes such as growth in fish, with relevance for both fish physiology research and environmental toxicology.

Introduction: The liver is a central metabolic regulator responsible not only for energy storage and allocation but also for the production of essential egg proteins. In seasonal breeders such as brown trout, physiological demands increase during spawning, requiring strong metabolic and structural adaptations. Understanding the cellular mechanisms underlying these fluctuations is essential for clarifying how liver function is regulated during reproduction. Objective: The aim of this study was to investigate cellular mechanisms underlying liver remodelling during the reproductive cycle of male and female brown trout by examining proliferation and apoptosis markers at both molecular and protein levels during four distinct reproductive stages: spawning capable, regressing, regenerating, and developing. Methodology: Adult male and female brown trout were sampled at four reproductive stages. Liver gene expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analysed using qRT-PCR. At the protein level, liver tissue sections were immunolabelled with antibodies against PCNA and caspase-3. Caspase-3 staining intensity was quantified using ImageJ, while PCNA expression was assessed by counting positively stained nuclei. Results: PCNA gene expression was upregulated during the regressing stage, while PCNA-positive nuclei immunolabelling increased during the regressing and spawning-capable stages. Caspase-3 transcript levels showed no significant differences among stages, whereas immunostaining increased during regenerating and developing stages. Conclusions: Overall, the liver undergoes dynamic cellular remodelling throughout the reproductive cycle, balancing proliferation and apoptosis to meet reproductive demands. The results suggest that proliferation is more evident during regenerating stages, while apoptotic activity may be regulated post-transcriptionally. PCNA also indicates that proliferative activity may persist during spawning capable stages, reflecting ongoing mitotic readiness despite reduced overall proliferation.