Paracetamol (PARA) is a commonly used analgesic and antipyretic, but overdose can result in severe hepatotoxicity and nephrotoxicity. Aprepitant (APRE), a selective neurokinin-1 receptor (NK-1R) antagonist used clinically as an antiemetic, may offer protective effects against drug-induced organ toxicity. This study aimed to evaluate the renoprotective potential of APRE in a rat model of PARA-induced nephrotoxicity. In this study, 36 male Albino Wistar rats were randomly assigned to six groups: Healthy, PARA (2 g/kg), APRE (20 mg/kg), N-acetylcysteine (NAC) + PARA (140 mg/kg + 2 g/kg), APRE + PARA (10 mg/kg + 2 g/kg), and APRE + PARA (20 mg/kg + 2 g/kg). Twenty-four hours after PARA administration, tissue and blood samples were collected from all groups for biochemical and histopathological analyses. Serum BUN and creatinine levels increased in the PARA group, whereas they improved in the NAC and APRE groups. Renal superoxide dismutase (SOD) activity and glutathione (GSH) levels decreased, but NAC and APRE significantly improved these parameters. Moreover, while malondialdehyde (MDA) levels in kidney tissue increased in the PARA group, they were significantly reduced in the NAC and APRE groups. In addition, histopathological changes supported the biochemical findings. APRE may protect the kidneys against PARA-induced damage by reducing oxidative stress and improving antioxidant defenses.

Pharmaceutical products and the polymers used to manufacture them are often overlooked sources of microplastic (MP) exposure, with real implications for patient safety and the environment. Contamination arises from PE, PP, and PET packaging; elastomeric stoppers; plasticized PVC in IV bags and administration sets; excipients; and manufacturing-related contamination. The route of administration is important because injectables and IV infusions can deliver particles directly into systemic circulation, bypassing barriers that limit exposure via oral or topical routes.This review elaborates on leaching pathways driven by physical, chemical, interactive, and aging processes, as well as analytical methods, including optical and scanning electron microscopy, FTIR and Raman spectroscopy, and pyrolysis GC/MS, and emerging single-particle techniques differ in detection limits and face challenges from matrix interference and procedural contamination. Toxicological studies indicate that particle size, shape, and surface chemistry influence oxidative stress, and inflammatory responses. Nanoplastics are of particular concern due to their ability to cross biological barriers and enter cells, yet data on pharmaceutical-derived MPs and co-leaching additives (phthalate plasticizers, antioxidants, elastomer curing agents, residual catalysts) remain limited.Current pharmacopeial standards (USP <788>, <787>) classify particles only by size, ignoring polymer identity and excluding the submicron range. Extractables-and-leachables frameworks (USP <1663>, <1664>, ICH Q3E) address dissolved chemicals rather than intact particulate matter, leaving MPs insufficiently addressed by current regulations. Closing it requires packaging designed to shed less material from the outset, toxicokinetic data from real biological samples rather than models, longer-term in vivo and epidemiological studies, and contamination-free analytical workflows.

To investigate whether ultraviolet-C band (UVC)-induced photocatalytic activation enhances the toxic effects of titanium dioxide nanoparticles (TNPs) in their rutile (TNPs-R) and anatase (TNPs-A) crystalline forms, human hepatocytes L-02 and QGY-7703 were exposed to 25 nm TNPs-R or TNPs-A (80 μg/mL) with or without UVC irradiation for 20 or 40 min. Rates of cell division, necrosis, and apoptosis were analyzed via Giemsa staining. Additionally, C57BL/6 mice received an oral gavage of TNPs-A pre-irradiated with UVC for 1 h over 21 days; organ coefficients were assessed to evaluate systemic toxicity, and bone marrow polychromatic erythrocyte micronucleus (MN) rates were measured to evaluate genotoxicity. Results showed that both TNPs-R and TNPs-A significantly increased cell death and inhibited cell division in both cell lines (p <0 .05). UVC irradiation for 20 min exacerbated TNPs-R-induced necrosis and inhibition of cell division in both cell lines (p <0 .05). When the UVC exposure duration was extended to 40 min, TNPs-A induced significantly higher cell death rates (p <0 .01) and proliferation inhibition (p <0 .001) in both cell lines compared to TNPs-R. In mice administered UVC-TNPs-A, no significant changes in organ coefficients were observed; nevertheless, both the TNPs-A and UVC-TNPs-A groups showed elevated MN rates (p <0 .05), with the latter exhibiting the highest values. Our findings suggest that photocatalytic activation enhances the toxicity of TNPs both in vitro and in vivo. Furthermore, this toxicity is dependent on crystal form and UVC exposure duration: TNPs-R display stronger toxicity under short-duration UVC exposure, whereas TNPs-A exhibit greater toxicity following prolonged UVC irradiation.

Gentamicin-induced nephrotoxicity represents a major clinical limitation primarily mediated by oxidative stress, inflammation, and apoptotic pathways, prompting growing interest in protective natural antioxidants. Aronia melanocarpa L. berry extract is a rich source of bioactive polyphenols with potent cytoprotective properties. The aim of this study was to investigate the protective effects of Aronia melanocarpa L. berry extract against gentamicin-induced nephrotoxicity in rats by evaluating biochemical, oxidative stress, histopathological, and immunohistochemical parameters. Twenty-four male Wistar albino rats were divided into four groups: C (control, saline), GEN (100 mg/kg, IP), GEN + AME (100 mg/kg GEN + 200 mg/kg AME), and AME (200 mg/kg, orally). Following the 7-day experimental period, serum biochemical markers (BUN, urea, creatinine, uric acid), antioxidant enzyme levels (GPx, SOD, CAT), and systemic oxidant and oxidative stress status (MDA, TAS, TOS, OSI) were quantified. Additionally, renal tissues were evaluated for histopathological alterations and the immunohistochemical expression of TNF-α, HSP 27, and Caspase-3. HPLC-DAD analysis characterized AME as a rich source of phenolics (35.11 mg/g), primarily chlorogenic acid (16.86 mg/g) and rutin (7.73 mg/g). Gentamicin administration significantly impaired renal function (elevated BUN and creatinine, p < 0.05) and induced robust oxidative stress (increased MDA, TOS, and OSI, p < 0.0001; decreased GPx, p < 0.0001, and SOD, p = 0.0029). AME treatment significantly attenuated these biochemical alterations (p < 0.05), partially restored GPx levels (p = 0.0053), normalized CAT levels (p = 0.0003), and reduced gentamicin-induced elevations in MDA (p < 0.0001), TOS (p = 0.0013), and OSI (p < 0.0001). Standardized Aronia melanocarpa extract exhibits potent nephroprotective effects against gentamicin-induced nephrotoxicity. This protection is mediated through the modulation of oxidative stress, inflammation, and apoptosis (p < 0.05), likely due to the extract's high concentrations of chlorogenic acid and rutin.

Bisphenol A (BPA) is a prevalent endocrine disruptor, and bisphenol S (BPS), increasingly used as an alternative, is suspected of sharing similar biological activity. We investigated whether acute neonatal exposure to BPA and BPS affects sexual differentiation of the anteroventral periventricular nucleus (AVPV) and whether chronic developmental exposure impairs female reproductive physiology in Sprague-Dawley rats. For acute exposure, pups received four subcutaneous injections on postnatal days 1 and 2 (PND1-2) at 12-hour intervals. Experimental groups were vehicle (castor oil, 50 µL), estradiol (E2, 50 µg), BPA (250 µg), and BPS (250 µg). On PND19, the hypothalamus was isolated and analyzed for AVPV tyrosine hydroxylase (TH)-positive neurons and estrogen receptor alpha (ERα) expression. To assess chronic effects, female pups received daily subcutaneous injections from PND1 to 75 with vehicle, BPA (2 and 200 µg/kg), and BPS (2 and 200 µg/kg). Acute estradiol exposure significantly reduced TH-positive neurons, validating the model's sensitivity, whereas BPA and BPS did not significantly alter TH-neuronal density and estrogen receptor-α expression. However, chronic BPA and BPS exposure induced marked reproductive toxicity, including increased body weight, decreased ovarian and uterine weights, and a dose-dependent reduction in the gonadosomatic index. Folliculogenesis was disrupted, with fewer antral follicles and corpora lutea and greater follicular atresia, accompanied by reduced progesterone, elevated testosterone, and reduced myometrial thickness at higher doses. These findings indicate that despite the absence of measurable AVPV masculinization after acute neonatal exposure, chronic BPA and BPS exposure induced endocrine and reproductive toxicity. The comparable effects of BPS and BPA therefore call into question BPS as a safer substitute.

Smoking causes pigmentation changes and skin aging, according to epidemiological research. Nicotine affected melanogenesis and increased oxidative stress in primary human melanocytes from darkly pigmented (DP) and lightly pigmented (LP) skin. However, research on the effects of cigarette smoke condensate (CSC) on primary human melanocytes from light and dark pigmentations in an in vitro culture over long-term durations is lacking. Herein, CSC was tested on LP and DP melanocytes for 6 days. CSC suppressed tyrosinase activity and lightened LP and DP pellets, indicating melanin production suppression. However, CSC increased melanocyte dendricity in LP cells at 25, 50, and 100 µg/mL doses, indicating melanin export. In DP cells, CSC biphasically increased dendricity at 25 µg/mL and decreased it at 50 µg/mL. In CSC-free cultures, LP cells exhibit complete dendricity recovery at 25 µg/mL, partial recovery at 50 µg/mL, and further augmentation at 100 µg/mL. Dendricity in DP cells were recovered only at 25 µg/mL, not at 50 µg/mL. In LP cells, CSC increased ROS production and SA-β-gal staining, but in DP cells, ROS decreased and no senescence was seen. The data show that CSC concentration and melanocyte pigmentation affect melanocyte damage, oxidative stress, and senescence. Melanocytes from LP skin are more susceptible to CSC damage than DP skin.

Ochratoxin A (OTA) is a potent nephrotoxin commonly found in foods and feeds, with the kidney as its primary target organ. Apigenin (APG), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, may counteract OTA-induced renal damage. This study evaluated the preventive and post-exposure recovery effects of APG against OTA-induced nephrotoxicity in rats. Sixty adult male Sprague-Dawley rats were assigned to five groups (n = 12): control; APG (20 mg/kg bw/day); OTA-contaminated diet (10 mg OTA/kg diet); APG + OTA preventive group; and OTA + APG post-exposure recovery group. Serum kidney function biomarkers, electrolytes, inflammatory and apoptotic markers, malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), and superoxide dismutase (SOD) activity were measured. OTA induced nephrotoxicity, evidenced by elevated serum electrolytes, kidney function biomarkers, inflammatory and apoptotic markers, increased MDA and NO, decreased GSH and SOD activity, and renal tubular injury. APG treatment in both preventive and post-exposure recovery groups significantly reduced electrolytes, kidney injury, inflammatory and apoptotic markers, MDA, and NO, while increasing GSH and SOD activity compared with the OTA group; renal tubular lesions were also less apparent. In conclusion, APG attenuated OTA-induced nephrotoxicity, improving renal biomarkers, oxidative/nitrosative stress indices, inflammatory and apoptosis-related biomarkers, and renal histopathology. The preventive regimen showed greater overall improvement than post-exposure recovery; however, interpretation of the latter is limited by the absence of an OTA-recovery control group.

Triphenyltin hydroxide (TPTH) is a widely used agricultural fungicide and environmental pollutant well known for its potent toxicological potential. Despite this, its embryotoxic effects remain unexplored in avian models. This study presents a novel evaluation of TPTH's acute toxicity, genotoxicity, cytotoxicity, teratogenic potential, and enzymatic and tissue architectural potential using the in ovo chick embryo model. Fertilized chicken eggs were exposed to varying TPTH concentrations that further revealed a time-dependent median lethal dose (LD50) decline from 547.37 µg/egg at 24 h to 395.74 µg/egg at 96 h. Later, evaluations using 1%, 5%, and 10% of the 96 h LD50 demonstrated profound subcellular damage. The Hen's egg test for micronucleus (HET-MN) assay showed a significant dose-dependent induction of micronuclei, confirming genomic instability. Additionally, a reduced polychromatic to normochromatic erythrocyte (PCE/NCE) ratio indicated severe cytotoxicity and suppressed erythropoiesis. Morphometric assessments revealed teratogenic alterations, including heart tube failure, microcephaly, cranial edema, microphthalmia, localized hemorrhaging, and concentration-dependent growth retardation in body length, eye diameter, and limb elongation. Biochemical assessments revealed that TPTH triggers severe oxidative stress. This was supported by significant dose-dependent reductions in superoxide dismutase, catalase, and glutathione across major organs, alongside increased lipid peroxidation in the brain. Histopathological analysis also revealed severe toxicity. These findings validated that TPTH induces potent developmental toxicity through a cascade of genotoxic, cellular, enzymatic damage, and structural alterations, highlighting its extreme embryotoxic risks to avian populations and associated ecosystems.

Ethinylestradiol (EE2) and levonorgestrel (LNG) are synthetic hormones widely used in contraceptives and increasingly recognized as endocrine-disrupting contaminants. Although their individual reproductive effects are documented, their combined toxicity remains poorly understood. This study evaluated the sub-chronic reproductive toxicity of EE2 and LNG, administered alone or in combination, in male Wistar rats, with emphasis on potential non-additive endocrine-disrupting interactions. Animals were orally treated with EE2 (1 µg/kg bw), LNG (5 µg/kg bw), or both for four weeks. Individual exposures caused significant alterations in testicular weight, hormone levels, oxidative stress markers, and sperm quality, whereas epididymal weight was not significantly affected. In contrast, combined exposure markedly intensified these effects, causing severe spermatogenic impairment, near-complete sperm depletion, and major histological damage in testicular tissue. This enhanced toxicity was associated with increased lipid peroxidation, reduced antioxidant defenses, and marked suppression of testosterone, FSH, and LH levels, indicating disruption of the hypothalamic-pituitary-gonadal axis. Two-way factorial analysis confirmed statistically significant EE2 x LNG interactions for testicular weight, sperm concentration, sperm motility, LH and testosterone; in each case the observed combined effect was smaller than predicted by effect addition, indicating an infra-additive rather than synergistic interaction, consistent with a floor effect at these already substantial individual effect sizes. These findings highlight the importance of assessing combined endocrine disruptor exposures, as mixture effects modify reproductive toxicity in ways not predictable from single-compound data alone.

Methylene blue (MB) is a clinically important agent used for acquired methemoglobinemia and selected critical care indications, yet its effects during early embryogenesis remain poorly defined. This study evaluated developmental toxicity following in ovo MB exposure, characterized dose-dependent embryolethality, estimated the median lethal dose (LD50), and assessed developmental outcomes across a lower-dose range.An initial analytical cohort of 360 fertilized chicken eggs was allocated to two experimental phases. In the lethal-dose phase, MB was administered into the air chamber at doses 1, 2, 4, or 8 mg/kg. In the low-dose phase, MB was administered at doses of 0.067, 0.125, 0.250, or 0.500 mg/kg. Each phase included a sham-control group and a saline vehicle-control group. Embryonic mortality, developmental progression, relative embryo weight, crown-rump length, and hatch-related outcomes were recorded during incubation. Mortality data were analyzed using control-corrected probit regression. In the lethal-dose phase, mortality increased dose-dependently, reaching 23.3%, 43.3%, 90.0%, and 100.0% at 1, 2, 4, and 8 mg/kg, respectively. The estimated LD50 was 2.01 mg/kg, with a 95% confidence interval of 1.68-2.40 mg/kg. In the low-dose phase, MB concentrations from 0.067 to 0.500 mg/kg did not significantly affect mortality, relative embryo weight, or crown-rump length compared with controls. These findings indicate a steep lethal response to MB in this model, while 0.500 mg/kg may be regarded as a provisional no-observed-adverse-effect level (NOAEL) candidate under the present experimental conditions. Direct clinical extrapolation is limited because the in ovo model lacks maternal metabolism, placental transfer, and fetal clearance.

Bisphenol A (BPA) is a widely utilized endocrine-disrupting chemical that has been associated with metabolic dysregulation in various tissues. Nevertheless, its impact on ocular metabolism remains insufficiently understood. This study aims to investigate the metabolic effects of BPA exposure in ARPE-19 retinal pigment epithelial cells using untargeted metabolomics. ARPE-19 cells were exposed to 100 µM BPA for 24 hours, and cytotoxicity, intracellular reactive oxygen species (ROS) levels and glutathione metabolism parameters were identified. Metabolic alterations were analyzed utilizing liquid chromatography-quadrupole time-of-flight mass spectrometry (Q-TOF LC/MS). Principal component analysis (PCA), volcano plots, heatmaps, and pathway enrichment analysis were conducted to identify significantly altered metabolites and pathways. BPA exposure led to notable metabolic changes, including alterations in the tricarboxylic acid (TCA) cycle, β-oxidation, nucleoside metabolism, and amino acid metabolism. Key metabolite changes included increased levels of glutamine, pyroglutamic acid, anserine, and adenosine 2',3'-cyclic phosphate, suggesting oxidative stress and metabolic adjustment. Pathway analysis identified significant changes in arachidonic acid metabolism and pyrimidine metabolism, indicating oxidative stress and metabolic compensation due to BPA exposure. The findings underscore the metabolic risks of BPA exposure to retinal health and necessitate further validation through targeted metabolomics and in vivo studies.

Ethion insecticide is known for its neurotoxicity and due to its extensive usage, non- target species may suffer along with the targeted ones. Thus, its detrimental effects on non-target species need to be explored in depth. The present study aims to assess the ethion toxicity in non-target model Drosophila melanogaster using classical and molecular approaches. The two sublethal concentrations 1.25 and 1.88 ppm were selected based on the LC50 value and were used throughout the experiments. The detrimental effect of ethion on various life history traits increased with higher concentration. The phenotypic observations s evidenced deformities in egg, larvae and adult. The histological analysis revealed larval brain degeneration, loss of eye- imaginal disk nuclear features and extensive tissue damage in gut and Malpighian tubules. The preliminary RNAseq data analysis revealed that the upregulated differentially expressed genes (DEGs) in response to ethion were mostly associated with growth and development (TwdlM, TwdlL and Eip78C etc.), neurological behavior (ap, inaD, Galphaq, Rim, ple, ddc etc.), reproduction (Cp15, Cp16, Cp7Fa, Cp7Fb, dec, CG1077 etc.). Moreover, the downregulated DEGs are belong to the class of Mitochondrial Ribosomal Protein (MRP) gene family which regulate growth through mitochondrial translation and transcription. The top 25 hub genes among DEGs were found to have human orthologues, which are used as candidate genes in studying various human diseases. Thus, the study highlights attention to the concerning ecotoxicity and possible health hazards associated with insecticide usage especially to non-targets including humans.

As aquaculture intensifies, Nile tilapia Oreochromis niloticus is increasingly susceptible to parasitic infections. This study evaluated the safety and physiological effects of praziquantel (PQ) in tilapia. PQ was administered orally at 50 mg/kg (recommended dose) and 125 mg/kg biomass/day (supratherapeutic dose) for 3 days, and the effects were compared with a control group. Mortality in PQ-treated groups ranged from 0.67% to 4%. Plasma glucose increased dose-dependently on day 3 and returned to baseline in the recommended dose group by day 28 post-treatment. Calcium, chloride, and acetylcholinesterase levels decreased during dosing, with partial recovery observed subsequently. On day 3, reductions in erythrocyte, hemoglobin, and hematocrit levels were accompanied by increases in leucocyte and thrombocyte counts. The supratherapeutic dose group exhibited more pronounced cellular and nuclear alterations in erythrocytes. Oxidative stress biomarkers in liver and kidney tissues indicated organ-specific stress. Integrated Biomarker Response analysis revealed that a supratherapeutic dose induced greater biological disturbances. At the recommended dose, PQ residues in muscle and skin reached below detectable levels within 2 days, supporting a 2-day withdrawal period for consumer safety. However, some biological instabilities persisted beyond this period, suggesting incomplete physiological recovery and therefore, residue clearance alone does not confirm complete biological safety.

Dermal and mucosal surface exposure to mineral oils occurs in the occupational setting. To evaluate exposure levels at which toxicity occurs, we collected data on non-cancer toxicity of crude oil, refinery streams and refined mineral oils. This included extraction of no-observed-adverse-effect levels (NOAELs) and lowest-observed-adverse-effect levels (LOAELs). Concerning biokinetics, whole oils appear to have low skin penetration, while polycyclic aromatic hydrocarbon (PAH) fractions penetrate to a considerable extent. Concerning toxicity of crude oil, reported local effects in humans include skin rash and eczema. In animals, a LOAELSkin irritation was 0.4 mg/cm[2]. Systemic effects of crude oils include a LOAELDevelopmental effects of 30 mg/kg body weight (bw). Concerning refinery streams, local effects of syntower bottoms showed a LOAELSkin histopathology of 0.1 mg/cm[2]. Catalytically-cracked clarified oil had a LOAELIrritation of 3 mg/cm[2]; a systemic LOAEL on maternal body weight and developmental toxicity of clarified slurry oil was 1 mg/kg bw (NOAEL: 0.05 mg/kg bw). Systemic effects of refinery streams correlated with PAH content (mainly driven by one study). Concerning refined mineral oils, local effects reported in mechanics and metal workers include contact dermatitis, oil acne and nose and throat irritation (exposure involved used oils and other chemicals). A human LOAELskin occlusion of refined oil was 2 mg/cm[2]; in animals, skin irritation had LOAELs as low as 15 mg/cm[2] (NOAEL: 7.6 mg/cm[2]). Systemic effects of refined oils in rats included a LOAELDepressed body weight of 160 mg/kg bw. In conclusion, both local and systemic effects are observed after dermal exposure to mineral oils.