Search Results (169)

In Italy, the law on road homicide (Law no. 41/2016) introduced specific provisions for drivers who cause severe injuries or death to a person due to the violation of the Highway Code. The use of alcohol or drugs while driving constitutes an aggravating circumstance of the offence and provides for a tightening of penalties. Our study aims to report on the analysis performed on blood samples collected between January 2018 and December 2024 from drivers convicted of road homicide and who tested positive for alcohol and/or drugs. The majority of the involved subjects were males belonging to the 18–30 and 41–50 age groups. Alcohol, cocaine and cannabinoids were the most detected substances and the most frequent polydrug combination was alcohol and cocaine. We also investigated other influencing factors in road traffic accidents as the day of the week and the time of the day in which fatal road traffic accident occurred, and the time elapsed between the road accident and the collection of biological samples. Our data, in line with the international scenario, strongly support that, in addition to the tightening of penalties, raising awareness plays a key role in preventing alcohol- and drug-related traffic accidents by increasing risk perception and encouraging safer driving behaviors. Full article

HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis. Full article

Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article

Background: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to oxidative stress, apoptosis, and inflammation. Nanocurcumin (NCR) is a nano-formulated edition of curcumin with a higher therapeutic potential. NCR has demonstrated antioxidant and anti-inflammatory properties. Methods: This study is designed to inspect the potential validity of NCR on DOX-induced testicular damage in male rats. We used thirty-two Wistar albino rats (150–200 g) and divided them into four groups. NCR (80 mg/kg/ dissolved in 1% CMC) was given orally by oral gavage for 14 days. A single dose of DOX (15 mg/kg) (i.p.) was injected on the 7th day of the experiment. Results: DOX treatment reduced the sperm viability and motility rate, cellular antioxidants, and gonadal hormones; it led to higher levels of inflammatory mediators, necrosis, and sloughing in seminiferous tubules. Conversely, NCR treatment significantly alleviated these side effects by improving sperm count/motility and reducing sperm abnormalities. The testicular function recovery was likely driven by stimulating the cytoprotective SIRT1/NF-κB pathway, depressing the testicular level of oxidative indicators such as MDA, TNF-α, iNOS, IL-1β, and NO, and increasing levels of antioxidants such as GSH and SOD. In addition, NCR contradicted the apoptotic changes by downregulating the pro-apoptotic signals Bax and caspase-3, while inducing Bcl-2 upregulation. Moreover, NCR increased levels of gonadal hormones, attenuated histological abnormalities, and preserved testicular structure when compared with the DOX group. Conclusions: NCR treatment can effectively ameliorate DOX-induced testicular toxicity. Full article

With the continuous development of research on natural medicines, quinone compounds have become increasingly important in the research field of chemical constituents of natural treatments. However, there is a lack of in-depth and systematic collation of their types, distribution, pharmacological activities, and potential toxicities. This article comprehensively reviews the structural types, biogenetic pathways, extraction and separation methods, structural identification techniques, pharmacological activities, and toxicities of quinone compounds. It is found that the main difficulties in the research of quinone compounds lie in the cumbersome traditional separation and structural identification processes, as well as the insufficient in-depth studies on the mechanisms of their activities and toxicities. This review aims to provide a reference for research on quinone compounds in natural products and offer ideas and suggestions for subsequent in-depth exploration of the pharmacological activities of quinone compounds, prevention and control of their toxicities, and the realization of rational drug use. Full article

Drug toxicity prediction plays a crucial role in the drug research and development process, ensuring clinical drug safety. However, traditional methods are hampered by high cost, low throughput, and uncertainty of cross-species extrapolation, which has become a key bottleneck restricting the efficiency of new drug research and development. The breakthrough development of Artificial Intelligence (AI) technology, especially the application of deep learning and multimodal data fusion strategy, is reshaping the scientific paradigm of drug toxicology assessment. In this review, we focus on the application of AI in the field of drug toxicity prediction and systematically summarize the relevant literature and development status globally in the past years. The application of various toxicity databases in the prediction was elaborated in detail, and the research results and methods for the prediction of different toxicity endpoints were analyzed in depth, including acute toxicity, carcinogenicity, organ-specific toxicity, etc. Furthermore, this paper discusses the application progress of AI technologies (e.g., machine learning and deep learning model) in drug toxicity prediction, analyzes their advantages and challenges, and outlines the future development direction. It aims to provide a comprehensive and in-depth theoretical framework and actionable technical strategies for toxicity prediction in drug development. Full article

Metformin is the preferred first-line treatment for non-insulin-dependent diabetes mellitus, known for its benefits in cancer suppression, weight loss, and antiketogenic activity. It is a leading drug regarding mass distribution, and its high solubility in water leads to its significant accumulation in surface and groundwater. While some studies have explored its degradation products and toxicological consequences, none have specifically examined the impact of individual natural minerals and their mechanisms leading to these degraded compounds. Our investigation focuses on understanding the mineralogical effects of different photocatalysts and organic matter while assessing acute toxicity through cell viability tests on human cell lines. We utilized a custom-built reactor system containing metformin hydrochloride, photocatalysts, and organic matter under oxidizing conditions to explore the formation of new degraded compounds. We assessed the acute toxicity of both metformin hydrochloride and the resulting chemical mixture on kidney and liver cell lines using the colorimetric MTT cell viability assay. Despite the abundance of surface functional groups in organic humic acid, only solar energy-driven catalysts were found to effectively break down this widely used medication. Comparative analysis of metformin hydrochloride and its degraded residues indicates a toxic effect on liver cells. Our experiments contribute to understanding the environmental fate of metformin and pave the way for further biochemical investigations to identify toxicological mechanisms. Full article

Staphylococcus aureus is associated with human infections, being a resistant bacterium involved in serious infections, and its virulence and resistance are linked to oxidative stress. In this study, we review the role of oxidative stress in the pathogenesis of this bacterium and its influence on immune system evasion, antibiotic resistance, and pharmacological targeting. S. aureus infection generates an intense inflammatory response in the host, evidenced by the activation of pro-inflammatory pathways, the exacerbated production of reactive oxygen species (ROS), and cellular oxidative stress. However, the bacterium develops protective mechanisms against damage, including the production of endogenous antioxidants, the formation of biofilms, and the regulation of redox metabolism, favoring pathogenicity and drug resistance. Resistance seems to be related to alterations in redox metabolism, which influences the sensitization of the immune system. Modulation of the redox response has emerged as a promising approach for developing new antibiotics and formulating more effective combination therapies to combat resistant infections. Natural compounds, including flavonoids, terpenes, and quinones, have demonstrated antibacterial properties by inducing oxidative stress in S. aureus. In summary, the involvement of oxidative stress is complex, with an increase in ROS in the infection and a reduction in immune system evasion and resistance, which could be an interesting therapeutic target. Full article

Nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, has been associated with rare but potentially serious pulmonary toxicity, which can present in acute, subacute, or chronic forms. Acute toxicity typically manifests in the form of hypersensitivity pneumonitis, which is characterized by fever, dyspnea, and eosinophilia, often resolving rapidly after drug discontinuation. However, chronic toxicity can lead to interstitial lung disease with progressive fibrosis, causing significant and sometimes irreversible pulmonary impairment. The pathophysiology of nitrofurantoin-induced lung injury is thought to involve oxidative stress, immune-mediated mechanisms, and direct cytotoxic effects; however, the exact pathways remain incompletely understood. Clinical diagnosis is challenging due to nonspecific symptoms that often resemble other respiratory conditions, leading to delays in recognition and treatment. Radiographic findings vary, with acute cases showing diffuse ground-glass opacities, while chronic cases may demonstrate reticular interstitial changes and fibrosis. The discontinuation of nitrofurantoin is the primary intervention, but corticosteroids may be beneficial, particularly in chronic cases with persistent inflammation or fibrosis, though their efficacy remains uncertain. Given the risk of long-term respiratory complications, heightened awareness among healthcare providers is essential for early diagnosis and intervention. Future research is needed to better define risk factors, improve diagnostic criteria, and explore alternative treatment strategies that mitigate the potential for pulmonary toxicity while maintaining effective antimicrobial therapy. This review explores the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for nitrofurantoin-induced pulmonary toxicity. Full article

Cisplatin, a widely used chemotherapeutic agent, is known to induce premature ovarian insufficiency (POI) and infertility in women of reproductive age. Among the contributing factors, cisplatin-induced apoptosis of ovarian granulosa cells is considered a primary driver of ovarian dysfunction; however, the underlying mechanisms remain incompletely understood. In this study, we investigated the cytotoxicity of cisplatin on the granulosa cell line KGN in vitro and explored the associated mechanisms. Our results demonstrate that cisplatin induces KGN cell apoptosis in a dose-dependent manner and impairs mitochondrial function, as evidenced by excessive ROS production, membrane potential collapse, and reduced ATP synthesis. Mitophagy, a key cellular self-protection mechanism that selectively removes damaged mitochondria, was activated following cisplatin treatment, mitigating its detrimental effects on KGN cells. Activation of mitophagy with urolithin A (UA) ameliorated cisplatin-induced mitochondrial dysfunction and apoptosis, whereas inhibition of mitophagy with cyclosporine A (CsA) exacerbated these effects. Furthermore, pretreatment with the clinical drug melatonin significantly enhanced mitophagy, effectively attenuating cisplatin-induced apoptosis in KGN cells. This study proposes a novel therapeutic strategy for patients undergoing tumor chemotherapy, aiming to preserve treatment efficacy while reducing the adverse effects of chemotherapeutic agents on ovarian function, thereby improving patients’ quality of life. Full article

This study established a dual analytical workflow integrating thermal desorption–electrospray ionization–tandem mass spectrometry (TD-ESI-MS/MS) for rapid qualitative screening and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) for confirmatory quantification of 17 psychoactive substances and metabolites across six classes (opioids, amphetamine-type stimulants, cocaine, ketamine-type drugs, cannabinoids, and etomidate analogs) in hair matrices. Validation of the TD-ESI-MS/MS method demonstrated its sensitivity (limits of detection: 0.1–0.2 ng/mg) and precision (<19.3%), with matrix effects controlled to <19.6%. The TD-ESI-MS/MS method achieved an analysis time of 1 min per sample, enabling high-throughput screening with a sensitivity >85.7% and a specificity >89.7% for the 17 analytes. UPLC-MS/MS confirmation validated the screening results with accuracy rates of 89.7–99.8%. An analysis of specimens confirmed positive identified etomidate analogs as the predominant psychoactive substances (73.6%), with a lower prevalence of amphetamine-type stimulants (12.5%), ketamine-type drugs (9.0%), and opioids (2.8%). The polydrug use patterns identified concurrent etomidate–amphetamine consumption (n = 5) and complex analog combinations (etomidate–isopropoxate–metomidate, n = 13), suggesting evolving abuse trends. Despite limitations in the temporal resolution and representativeness of the cohort, this study demonstrated the viability of TD-ESI-MS/MS for bridging forensic and public health priorities. Future work should focus on optimizing the durability of the ion source for TD-ESI and validating this method across diverse populations to enhance its generalizability. Full article

One hazardous material that occurs naturally in the environment and induces oxidative stress is cadmium (Cd). Epidemiological data revealed that exposure to cadmium in the workplace and environment might be linked to many illnesses and serious testicular injuries. Aims: It is taught that antioxidants can protect different organs against environmental toxic compounds. Therefore, the current investigation aims to show the role of antioxidants (gallic acid and selenium) in the protection against cadmium toxicity, including the architecture of the testes, semen properties, steroid hormones, protein expression of cytochrome P450 [CYP 19 and 11A1] contributing to the production of steroid hormones, and antioxidant enzyme activities, in male rabbits. Methods: Male rabbits were given cadmium orally three times/week [1 mg/kg BW] for twelve weeks. In addition, gallic acid (20 mg/kg) or selenium (1 mg/kg BW) was administered two hours before cadmium treatment. This investigation included a spectrophotometer, histopathology, and Western immunoblotting techniques. Results: Cadmium treatment significantly reduced sperm counts, testosterone, and estrogen levels after four, eight, and twelve weeks of treatment. In addition, after a 12-week treatment of rabbits with cadmium, the activity of 17β-hydroxysteroid dehydrogenase and antioxidant enzymes, including catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, as well as the glutathione levels, were inhibited in the testes tissue. On the other hand, following cadmium treatment, rabbit’s testes showed a discernible increase in free radical levels. Interestingly, the activity of antioxidant enzymes and level of free radicals were recovered in rabbits treated with gallic acid or selenium before cadmium treatment. In addition, after 12 weeks of cadmium treatment, the steroidogenic protein expressions of CYP 11A1 and CYP 19 were upregulated and downregulated in the testes, respectively. Interestingly, after pretreatment of rabbits with either gallic acid or selenium for two hours before cadmium administration, the downregulated CYP11A1 was restored to normal levels. In the histopathological investigation, immature spermatozoids and sloughed spermatogonium cells were observed in cadmium-treated rabbits’ testes. On the other hand, pretreatments of rabbits with gallic acid or selenium mitigated and alleviated the adverse effects of cadmium on testes architecture and increased the production of healthy sperm. Conclusions: The lower levels of steroid hormones could be due to the downregulation of CYP11A1, inhibition of 17β-hydroxysteroid dehydrogenase, antioxidant enzyme activities, and the induction of free radical levels. Furthermore, the pretreatment of rabbits with gallic acid or selenium mitigated the adverse effects of cadmium on the tissue architecture of testes and steroid hormone levels. Full article

Lead is a harmful heavy metal known to alter the environment and affect human health. Several industries have contributed to the increase in lead contamination, making it a major global concern. Thus, remediation strategies are necessary to prevent lead bioaccumulation and deleterious health effects. The aim of this study was to determine the capacity of the green microalga Chlorella vulgaris (C. vulgaris or CV) to remove lead in an animal model and prevent the accumulation of this heavy metal in the principal organs (brain, liver, and kidney) and blood. Forty male Wistar rats were randomly assigned to four groups (n = 10): control group (CT); C. vulgaris supplementation group, 5% of the diet (CV); lead acetate administration group, 500 ppm (Pb); and C. vulgaris supplementation group, 5% of the diet plus lead acetate administration group, 500 ppm (CV–Pb). After 4 weeks of exposure, we measured lead accumulation, memory function, oxidative stress, and antioxidant activity (SOD and GSH). Lead exposure altered memory function, increased oxidative stress in the brain and kidney, and increased SOD activity in the brain. Supplementation with C. vulgaris restored memory function to control levels; reduced oxidative stress in the brain and kidney; and decreased the accumulation of lead in the liver, kidney, and blood of rats exposed to lead. Based on our results, C. vulgaris is a lead chelating and antioxidant agent in animal models. Full article

Doxorubicin (DOX) is used for the treatment of various malignancies, including leukemias, lymphomas, sarcomas, and bladder, breast, and gynecological cancers in adults, adolescents, and children. However, DOX causes severe side effects in patients, such as cardiotoxicity, which encompasses heart failure, arrhythmia, and myocardial infarction. DOX-induced cardiotoxicity (DIC) is based on the combination of nuclear-mediated cardiomyocyte death and mitochondrial-mediated death. Oxidative stress, altered autophagy, inflammation, and apoptosis/ferroptosis represent the main pathogenetic mechanisms responsible for DIC. In addition, in vitro and in vivo models of DIC sirtuins (SIRT), and especially, SIRT 1 are reduced, and this event contributes to cardiac damage. In fact, SIRT 1 inhibits reactive oxygen species and NF-kB activation, thus improving myocardial oxidative stress and cardiac remodeling. Therefore, the recovery of SIRT 1 during DIC may represent a therapeutic strategy to limit DIC progression. Natural products, i.e., polyphenols, as well as nano formulations of DOX and iron chelators, are other potential compounds experimented with in models of DIC. At present, few clinical trials are available to confirm the efficacy of these products in DIC. The aim of this review is the description of the pathophysiology of DIC as well as potential drug targets to alleviate DIC. Full article