Pesticide exposure is a growing public health concern, particularly in agricultural regions where workers and communities encounter multiple chemical compounds simultaneously. Although previous studies have investigated the reproductive toxicity of individual pesticides, the combined effects of commonly co-applied insecticide-fungicide mixtures remain poorly characterized. We hypothesized that the simultaneous administration of lambda-cyhalothrin, emamectin benzoate, and thiophanate-methyl, three pesticides routinely co-applied in eastern Algerian agriculture, would exert synergistic reproductive toxicity in male rats, exceeding the effects observed with each compound alone. Seventy-two adult male Wistar rats (n = 8 per group) were treated by oral gavage for 6 weeks with each pesticide at 1/20 LD50 (high dose) or 1/60 LD50 (low dose), or with a ternary mixture at the same dose levels; one group served as the control. Testicular and epididymal weights, plasma testosterone concentration, sperm parameters (concentration, motility, and speed), oxidative stress markers (GSH, GPx, and MDA), and tissue histopathology were evaluated. All three pesticides at the high dose significantly impaired reproductive parameters and induced oxidative stress; however, the mixture group (G8, 1/20 LD50) exhibited the most pronounced alterations, including a highly significant decrease in testicular weight, severe testosterone suppression, marked sperm parameter decline, and extensive histopathological damage consistent with synergistic toxicity. These findings provide the first evidence that the combination of lambda-cyhalothrin, emamectin benzoate, and thiophanate-methyl produces synergistic reproductive toxicity in male rats, underscoring the need for mixture-based risk assessment in agricultural pesticide regulation.
Aluminium phosphide (AlP) is a well-known toxic pesticide, but its dose-dependent toxicity and the distinction between safe and harmful exposure levels remain poorly established. Thus, the present study aimed to investigate the dose-dependent toxicity of AlP on biochemical biomarkers, antioxidant defense responses, and histological changes in rat liver and kidneys. Adult male Wistar rats were treated orally with increasing AlP doses (0.38, 0.58, and 1.15 mg/kg body weight, corresponding to LD50/30, LD50/20, and LD50/10, respectively) for 4 weeks. Results revealed a marked increase in body weight, serum levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), and PAL (alkaline phosphatase), and levels of urea, creatinine, and malondialdehyde (MDA) of treated rats as compared with controls. However, glutathione content and enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) in liver and kidney tissue were significantly decreased compared with controls. These biochemical changes following AlP treatment also mirrored hepatic and renal histopathological observations, showing dose-dependent tissue alterations, with a more pronounced effect in the higher AlP dose-treated rats. Conclusively, sub-acute AlP exposure caused dose-dependent liver and kidney toxicity, high doses induced pronounced damage, and low doses showed mild or minimal effects.
Formaldehyde (FA) is a widely used chemical with known carcinogenic properties, particularly for the upper respiratory tract. Concerns about probable FA-induced hematotoxicity and leukemia have sparked investigations into its health risks. This review scrutinized the quality of exposure evaluations in studies exploring the hematotoxicity of FA and assessed the association between FA exposure and blood dyscrasias. A total of 22 studies were included in the systematic review; among them, 10 provided sufficient data for meta-analysis. FA exposure was significantly associated with changes in blood parameters, including white blood cells (standardized mean difference [SMD] = -1.450 ± 0.636), T cytotoxic cells (SMD = 2.813 ± 1.013), and natural killer (NK) cells (SMD = 1.911 ± 0.775). None of the other blood parameters were significantly affected. However, because of inconsistencies and limitations in exposure assessment methods across the reviewed studies, a clear dose-response relationship could not be established. Overall, changes in some blood parameters were possibly a response to the sensory irritation of FA in the upper respiratory tract. Based on the available scientific evidence, inhaled FA is not distributed beyond portal-of-entry to distal tissues or organs. It is recommended that the exposure of workers to FA be evaluated in a more comprehensive way by following well-validated FA sampling and analysis methods in future studies to better elucidate the association between FA exposure and hematotoxicity. Also, biological monitoring is recommended to estimate overall worker exposure to formaldehyde and to assess the association between FA exposure and its probable hematotoxicity.
Flurochloridone (FLC) was classified as "May cause harm to the unborn child" by the European Food Safety Authority (EFSA). Because of the potential for occupational exposure to FLC, and the lack of reported maternal and fetal data, we investigated the effects of FLC on sex hormones, toxicokinetics, and maternal well-being, as well as fetal development. Thirty-two pregnant Sprague-Dawley rats were divided into four groups: a vehicle control group and three FLC-treated groups (3, 10, and 30 mg/kg, respectively). FLC was administered to the dams via oral gavage from gestation day (GD) 0 to GD 20. Six dams in each group were used for toxicokinetic evaluations. Cesarean sections were performed on GD 21. Additionally, blood samples were collected for hormone analysis. We found that pregnancy decreased the clearance rate and increased the absorption of FLC in rats. In the 30-mg/kg group, FLC significantly reduced maternal heart weight and decreased testosterone and progesterone levels with no adverse effect on maternal fertility. FLC had no adverse effect on visceral development, but caused a significant increase in incomplete ossification of the fetal sternum in the 30-mg/kg group. In the present study, the no-observed-adverse-effect level (NOAEL) of FLC on embryo-fetal development was estimated to be 10 mg/kg/day.
Perfluorooctane sulfonate (PFOS) is a man-made chemical widely used in many products and acts as an endocrine-disrupting chemical (EDC). PFOS has spread to the environment through industrial manufacturing processes and disposal of PFOS-containing products. There is growing evidence that environmental pollutants may have promoting effects on cancer cell aggressiveness, rapid growth, and metastasis. Thyroid cancer is an endocrine-related cancer that can respond to EDCs. This study aimed to explore the effect of PFOS on the growth and metastatic potential (invasion capability) of FTC-133 human thyroid cancer cells. PFOS exposure for 72 h (1 pM to 10 µM) did not stimulate growth of FTC-133 cells. However, PFOS exposure at low concentration (1 nM) enhanced invasion capability of the cells, with no correlation to the expression level of estrogen receptors. FTC-133 cells exposed to 1 nM PFOS displayed increasing phosphorylation of multiple invasion-related signaling proteins, including Akt, ERK, and EphA2. Our study revealed that PFOS at low concentration may influence thyroid cancer progression by increasing the metastatic potential of cancer cells.
The potential of the neonicotinoid insecticide dinotefuran to induce oxidative DNA damage was evaluated in human peripheral blood lymphocyte cultures at three concentrations (0.05, 0.15, and 0.30 µg/mL) using the single-cell gel electrophoresis assay (COMET). Its ability to interact with DNA was further examined through molecular docking analysis. The comet assay results revealed statistically significant increases (p < 0.001) in both the genetic damage index (GDI) and the percentage of heavily damaged cells (DCP) at all tested concentrations compared with the negative control. DNA damage within individual cells caused by genotoxic agents can thus be effectively detected using the comet assay, as demonstrated in our study. Additionally, the optimized molecular structure, total energy, molecular orbital energies, molecular electrostatic potential (MEP) maps, and global reactivity parameters of dinotefuran were obtained using the DFT/B3LYP/6-311G(d,p) method. The fully optimized energy was predicted, and geometric parameters were compared with available single-crystal structure data. Computational studies employing density functional theory (DFT) and MEP analyses provided detailed insights into the geometric and electronic characteristics of dinotefuran, suggesting that the compound possesses significant chemical reactivity and potential for biological activity upon interaction with DNA. Molecular docking studies with the B-DNA dodecamer (PDB ID: 1BNA) yielded a minimum binding energy of -6.24 kcal/mol. Dinotefuran was found to form four conventional hydrogen bonds, two carbon-hydrogen bonds, and one π-donor hydrogen bond with DNA, primarily involving guanosine, cytosine, and thymidine bases. These interactions are consistent with the experimental evidence of genetic-oxidative DNA damage, indicating that dinotefuran can establish strong molecular interactions with DNA.
Environmental pollutants are an important cause of depression. Dibromoacetonitrile (DBAN) is a disinfection by-product, which is neurotoxic and induces oxidative stress. This study aimed to elucidate whether and how DBAN provoked depression-like behavior. Mitogen-activated protein kinase phosphatase-1 (MKP-1) and P38 mitogen-activated protein kinase (MAPK) are key factors in depression. In mice, 8-week gavage with 20 mg/kg DBAN caused depressive symptoms, serotonin (5-HT) loss, hippocampal neuronal damage, and elevated MKP-1/P38 MAPK signaling; 80 mg/kg proved lethal. DBAN disturbed the intestinal flora of mice. Depression-related bacteria Firmicutes increased. Bacteroidota showed a decreasing trend, and the relative abundance of Bifidobacterium also showed a decreasing trend. Co-treatment with antioxidant N-acetylcysteine (NAC, 150 mg/kg) prevented mortality, restored 5-HT and norepinephrine, normalized MKP-1/P38 phosphorylation, and alleviated behavioral deficits. 10 μM DBAN raised reactive oxygen species (ROS), upregulated MKP-1, increased the phosphorylation levels of P38 and c-Jun amino-terminal kinase (JNK), and decreased the phosphorylation levels of the extracellular signal-regulated kinase (ERK1/2) in HT22 cells. Following HT22 cell MKP-1 knockdown and DBAN exposure, HT22 cells exhibited decreased MKP-1 expression along with decreased P38 and JNK phosphorylation levels. Still, the levels of ERK1/2 phosphorylation were not significantly affected. NAC exerts a prophylactic protective effect against these adverse outcomes.
γ-Hexachlorocyclohexane (γ-HCH) is a persistent organochlorine pesticide widely used in agriculture and public health. While its neurotoxicity in humans and animals is well documented, its toxic effects on non-target organs, particularly the lungs, remain poorly understood. In the general population, diet is the primary route of γ-HCH exposure; however, the long-term effects of dietary exposure on pulmonary immunity remain poorly understood. This study employed a two-hit murine model to determine whether prolonged oral exposure of γ-HCH alters pulmonary immune responses to a secondary inflammatory challenge. Swiss albino male mice were administered γ-HCH orally (0.12 mg/kg body weight) for 60 or 90 days, followed by an acute intranasal lipopolysaccharide (LPS) challenge at the respective terminal time points. Systemic and local inflammatory responses were assessed by quantifying cytokine levels (IL-1β and TNFα) in serum and bronchoalveolar lavage fluid using ELISA. Lung tissues were assessed for TLR4 and TNFα expression by immunohistochemistry and examined ultrastructurally by transmission electron microscopy. Subchronic γ-HCH exposure led to a significant increase in IL-1β and TNFα levels, accompanied by robust expression of these markers in pneumocytes, alveolar epithelial cells, and vascular endothelium. Upon LPS challenge, γ-HCH-treated mice showed exacerbated pulmonary inflammation with histopathological changes. Interestingly, the inflammatory response in γ-HCH + LPS groups was not consistently greater than that in the LPS-only group; in some cases, cytokine levels were moderately reduced. These findings suggest that subchronic dietary γ-HCH exposure primes the immune system and alters pulmonary inflammatory responsiveness to a subsequent endotoxin challenge. This pattern is consistent with immune modulation rather than amplified protective immunity. While the observed responses are associated with activation of innate immune signaling pathways, including TLR4-linked mechanisms, further functional studies are required to establish causal relationships. Overall, this study underscores the importance of cumulative and sequential environmental exposures when assessing immunotoxic potential of persistent organic pollutants.
Objective Mitochondrial dysfunction is the key factor in rotenone-induced neurotoxicity in dopaminergic neurons. This study aimed to investigate the role and potential mechanism of the mitochondrial DNA encoded peptide Humanin (HN) in alleviating rotenone-induced neurotoxicity.Methods Rotenone was added to the cultured PC12 cells to induce neurotoxicity. PC12 cells were preincubated with HN, which has a protective effect. Cell counting kit-8 (CCK-8) was used to evaluate PC12 cell viability. Flow cytometry to detect the content of reactive oxygen species (ROS) in PC12 cells. Western blot analysis was used to detect the expression of superoxide dismutase 2 (SOD2), acetylated SOD (Ac-SOD), sirtuin 3 (SIRT3), nuclear factor erythroid 2-related factor 2 (Nrf2), heme-oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The corresponding kits were used to measure the NAD+/NADH ratio and SOD content separately.Results HN pretreatment significantly increased PC12 cell survival, reduced ROS formation, and increased the NAD+/NADH ratio. It also increased the expression of SIRT3, Nrf2, HO-1, and NQO1 proteins and decreased the expression of Ac-SOD protein under rotenone exposure. At the same time, it also activated the Nrf2/HO-1 signaling pathway, which depends on HN-mediated SIRT3 activation.Conclusion These results suggest that HN plays a protective role in rotenone-induced neurotoxicity by suppressing oxidative stress and activating the antioxidant response via the Nrf2/HO-1 pathway, which is regulated by SIRT3 in PC12 cells.
Fine particulate matter (PM2.5) deposition in the lungs can induce pulmonary injury. Histone deacetylase 6 (HDAC6), a critical member of the histone deacetylase family, plays a key role in regulating lung diseases. In this study, we explored the mechanism of HDAC6 in PM2.5 (10 mg/kg)-induced pulmonary injury using an HDAC6 knockout (KO) mouse model, employing immunohistochemical, western blot, and transcriptome analyses. Results indicated that HDAC6 KO exacerbated PM2.5-induced epithelial barrier dysfunction by altering the expression of zonula occludens-1 (ZO-1) and zonula occludens-2 (ZO-2). Moreover, HDAC6 KO increased the susceptibility of lung tissue to PM2.5 by inhibiting E-cadherin expression and promoting N-cadherin expression. Transcriptome analysis of PM2.5-treated lungs in the HDAC6 KO group revealed significant alterations in the renin-angiotensin system (RAS). The expression levels of RAS components, including angiotensin-converting enzyme II (ACE2), angiotensin II (Ang II), renin, and Agtrl1b, were quantified. Notably, both PM2.5 and HDAC6 KO disrupted RAS balance. The PM2.5-treated HDAC6 KO group exhibited a pronounced reduction in ACE2 and elevation in Ang II, suggesting increased susceptibility to PM2.5. These results indicate that HDAC6 KO exacerbates PM2.5-induced pulmonary injury by affecting RAS balance. This study provides a theoretical foundation for understanding the role of HDAC6 in PM2.5-induced pulmonary injury.
Paraquat (PQ), a widely used herbicide, induces severe pulmonary fibrosis through complex mechanisms that are not fully understood. This study employed an integrated computational approach combining network toxicology, molecular docking, dynamics simulations, and AlphaFold2-based protein design to systematically investigate PQ-induced pulmonary fibrotic processes. We identified 111 common targets from pulmonary fibrosis and PQ toxicity databases, among which AKT1, IL6, TP53, and CASP3 were recognized as core targets. Functional enrichment analyses revealed significant involvement of oxidative stress, inflammatory response, and apoptotic pathways. Molecular docking demonstrated strong binding affinity between PQ and key targets (docking scores < -5 kcal/mol), while molecular dynamics simulations confirmed stable interactions with favorable binding energies (< -12 kcal/mol). Furthermore, AlphaFold2 predicted three novel proteins exhibiting even higher binding affinity to PQ than natural targets. These findings reveal that PQ might promote pulmonary fibrosis by stably binding to core proteins and activating critical pathological pathways, providing valuable insights for developing targeted biomarkers and therapeutic strategies against PQ-induced lung injury.
Endocrine-disrupting chemicals (EDCs), including heavy metals such as lead (Pb), interfere with hormonal homeostasis, particularly in the hypothalamic-pituitary-gonadal (HPG) axis. Occupational lead exposure is linked to male reproductive dysfunction and cardiovascular risk via oxidative stress and endothelial impairment. This study investigated the effects of chronic lead exposure on testosterone levels and the L-arginine-nitric oxide (NO) pathway, a key regulator of endothelial function. This case-control study compared 120 male workers with occupational lead exposure (in battery manufacturing and foundries) to 120 unexposed controls. Blood lead levels (BLLs) were quantified via inductively coupled plasma mass spectrometry (ICP-MS), while testosterone (total/free) and methylated arginine metabolites; asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and citrulline were analyzed using LC-MS/MS. Statistical analyses included t-tests and Pearson correlations to assess associations. Lead-exposed workers had significantly higher BLLs (31.76 ± 13.31 vs 1.72 ± 0.87 μg/dL), lower total testosterone (388.23 ± 71.78 vs 477.36 ± 104.21 ng/dL), and reduced arginine/ADMA ratios (432.48 ± 191.27 vs 544.33 ± 187.19), indicating endothelial dysfunction. Strong inverse correlations were observed between exposure duration, classified as 6 months to 1 year, 1 to 5 years, and >5 years, to evaluate its association with BLL, testosterone levels, and arginine metabolism markers. This study demonstrated that chronic occupational lead exposure significantly disrupted testosterone secretion and impaired the L-arginine-NO pathway, highlighting its dual threat to reproductive and cardiovascular health. The robust inverse correlations between BLL, testosterone, and arginine/ADMA ratios underscore the endocrine-disrupting and endothelial-damaging effects of lead. These findings support the routine biomonitoring of BLL, testosterone, and methylated arginine metabolites in high-risk occupations to enable early intervention and mitigate long-term health risks.
4-Nonylphenol (4-NP), an endocrine disruptor, is known to induce mutagenic, toxic, or carcinogenic effects, including testicular toxicity via inducing oxidative stress and apoptosis. The objective of this work was to determine the capacity of lycopene (LC) and gallic acid (GA) to protect testicular histological structure, biochemical responses, and semen parameters in rats exposed to 4-NP. In this 28-day dietary trial, six groups (n= 6 per group) received treatment via oral gavage: a control (corn oil, 2 mL/kg/day), LC (10 mg/kg body weight (BW)/day), GA (50 mg/kg BW/day), 4-NP (125 mg/kg BW/day), LC + 4-NP (LC followed by 4-NP), and GA + 4-NP (GA followed by 4-NP) groups. The results indicated that 4-NP administration adversely affects the final body weight, testicular histology, seminiferous epithelium heights (SEHs) (4-NP: 57.95 ± 0.49, p: 0.000), follicle-stimulating hormone (FSH) level, testis antioxidant capacity, testis malondialdehyde (MDA) level, and sperm viability and morphology. LC and GA supplementation significantly improved SEHs, activities of testis superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and sperm viability compared to the 4-NP group. Moreover, LC and GA exposures decreased histopathological lesions, including germinal epithelial degeneration, vacuolization, immature germ cells in the tubular lumen, and congestion in the interstitial area. Furthermore, they lowered TUNEL-positive cell counts and tubule percentages, testicular MDA levels, and abnormal sperm percentages. To our knowledge, this study provides one of the first systematic comparisons of lycopene and gallic acid in protecting against 4-NP-induced testicular toxicity under identical experimental conditions. The findings suggest that both compounds preserve testicular structure and function through their antioxidant and anti-apoptotic properties.
Tetrabromobisphenol-A (TBBPA) is found in high concentrations in textiles, plastic polymers, flame retardants, and various industrial products. In this maternofetal study, we aimed to evaluate the potential effects of TBBPA on the mother, fetus, and placenta in pregnant rats. In the experimental design, three different gestational days (GD10, GD15, and GD20) were selected for evaluation in pregnant rats. For each gestational period, one control group (corn oil) and three TBBPA dose groups (20, 200, and 400 mg/kg) were established, resulting in a total of 12 experimental groups. Each group included six pregnant rats. We hypothesized that TBBPA exposure would lead to alterations in maternal and fetal hormonal and placental parameters when evaluated across different doses and gestational days. Placenta, kidney, liver, and ovary tissues were examined histopathologically. Levels of follicle-stimulating hormone (FSH), progesterone, luteinizing hormone (LH), and estrogen were analyzed. Estrogen from ovarian homogenates and testosterone from testicular homogenates of GD20 fetuses were also measured. We detected statistically significant differences in placental and fetal data. However, no severe effects were observed. Serum FSH levels were elevated in the GD20 group receiving 400 mg/kg, whereas LH levels increased in the GD15 group at both 200 and 400 mg/kg compared to controls. In GD20 female fetuses, estrogen levels decreased at 20 mg/kg but increased at 200 mg/kg relative to the control group. Histopathological examination of placental tissue revealed congestion, degeneration in the labyrinth region, cytoplasmic dissolution and pyknosis in giant cells, and degeneration in spongiotrophoblasts. No severe systemic toxicity was observed in our study. However, the mild to moderate level changes detected highlight the need for further investigation of TBBPA, especially considering the uncertainties regarding its effects during pregnancy.
Bisphenol analogues are commonly found in various consumer products such as food and beverage containers, electronic devices, toys, paper products, water pipes, and medical equipment. These compounds have been shown to disrupt endocrine function and exert harmful effects on multiple body organs. To investigate the tissue- and DNA-damaging effects of varying oral doses of Bisphenol Z (BPZ), a study was conducted on Wistar rats over a 4-week period. After 28 days, the rats were dissected, and tissue samples were collected. Tissue histology, Comet assay, and real-time PCR were performed to assess the effects of BPZ at the tissue and genomic levels. Sperm count and motility were significantly reduced in groups exposed to higher doses of BPZ (mean ± SD: 27.00 ± 7.94 and 4.33 ± 0.43, respectively). Morphologically abnormal sperm, including deformed heads and curly tails, were observed. The Comet assay on testicular tissues from rats treated with higher BPZ doses showed clear signs of DNA fragmentation. Histopathological analysis revealed narrowing of the interstitial spaces and constriction of the epididymal lumen. Additionally, down regulation of the Protamine1 gene was observed in rats receiving higher doses of BPZ, significantly associated with spermatogenesis. Our findings not only highlight the severity of BPZ's toxic effects but also emphasize that these chemicals are unsafe in any analogue form.
This study investigated the protective effects of taurine against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cardiotoxic damage in rats. Adult male Wistar rats (250-300 g) were randomly assigned to four groups (n = 8 per group): Control, TCDD, TAU, and TCDD + TAU. TCDD (2 μg/kg/week) and/or taurine (200 mg/kg/day) were administered via gavage for 30 days. Following the experimental period, heart tissue samples were collected for analysis. Oxidative stress parameters, including thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) activity, and glutathione (GSH) levels, were assessed using biochemical methods. Histopathological and immunohistochemical evaluations of cardiac tissue were also performed. The TCDD group showed significantly increased TBARS levels (p < 0.05) and decreased SOD activity and GSH levels (p < 0.001) compared with the Control group. In contrast, taurine co-administration significantly increased SOD activity and GSH levels while reducing TBARS levels relative to the TCDD group. Moreover, TCDD exposure induced marked histopathological alterations in heart tissue, whereas taurine co-administration attenuated these structural alterations. Immunohistochemical findings indicated that taurine attenuated TCDD-induced apoptosis by reducing caspase-3 activation. Overall, taurine effectively mitigated TCDD-induced oxidative stress, histopathological damage, and apoptotic signaling in cardiac tissue, suggesting that taurine co-administration may exert protective effects against TCDD-induced cardiotoxicity.
E-waste contains over a thousand different substances, most of which are toxic and hazardous to human health. This study aimed to determine the blood levels of cadmium (Cd) and lead (Pb) among e-waste workers, and the possible health symptoms associated with chronic low dose occupational exposure to e-wastes. This was a cross-sectional study carried out among 80 individuals aged 25 years and above. Forty-two of the participants were e-waste workers and 38 were non-e-waste workers. Demographic characteristics and anthropometric data were obtained from each participant. Blood lead levels (BLLs) and blood cadmium levels (BCLs) were measured in all the participants using atomic absorption spectrometry (AAS). The mean BLL and BCL were significantly higher in the e-waste workers than in the non-e-waste workers. Most of the e-waste workers (76.2%) performed phone and laptop repairs. They reported chest pain (19.0%), abdominal pain (9.5%), throat irritation (2.4%), and cough (9.5%) as common symptoms experienced at work. Many of the e-waste cohort (73.8%) worked in poorly ventilated rooms and many (95.2%) were also involved in crude and unregulated e-waste recycling processes. In conclusion, the results from our study suggested that elevated BLL and BCL in the e-waste workers were from occupational exposure associated with crude e-waste recycling processes, and these elevated levels were probably associated with the adverse health effects in this group of workers. Continuous training and awareness of safe occupational practices is highly recommended among the e-waste workers.
This study aimed to investigate the effects of high-frequency (6 GHz) radiofrequency electromagnetic radiation (RF-EMR) exposure on oxidative stress markers and kidney morphology. Our study was designed with 3 groups, each containing 10 animals. These groups were: control, sham, and RF-EMR exposed group. No treatment was applied to the control group; the sham group was housed in the same room under the same conditions and for equal periods of time, except that the generator was turned off. The RF-EMR exposed group was exposed to 6 GHz RF-EMR emitted from the signal generator for 4 hours per day for 6 weeks. At the end of the experimental period, intracardiac blood was collected from animals and plasma oxidant (MDA), antioxidant (SOD, CAT and GSH) and cortisol markers were analyzed. After, the rats in all groups were sacrificed and kidney tissues were removed. Hematoxylin and eosin staining methods were applied histopathologically. Blood-plasma GSH, CAT, SOD and MDA levels (excluding cortisol) were lower in the RF-EMR exposed group compared to the control and sham groups (p < .001). No significant difference was observed in plasma levels GSH, CAT, SOD, MDA and cortisol activities between control and sham groups. In addition, we reported that the histological characteristics of kidney tissue were affected by RF-EMR. The results of our study indicated that 6 GHz RF-EMR can function as an environmental stress factor and can modulate oxidative stress in blood plasma and cause morphological changes in kidney tissue.
Human exposure to triazole fungicides such as flutriafol (FFL) is raising concerns regarding their potential toxic effects. FFL has been reported to induce oxidative stress and systemic toxicity, yet its subacute effects remain incompletely characterized. This study investigated the subacute oral toxicity of FFL in adult male mice, with a particular focus on behavioral, biochemical, hematological, and histological alterations. Behavioral assessment and median lethal dose (LD50) determination were performed initially. Mice were then administered FFL by oral gavage at doses of 25, 50, 75, or 100 mg/kg body weight for 15 consecutive days. Hematological indices and biochemical parameters reflecting hepatic, renal, cardiac, and lipid metabolic function were evaluated. Oxidative stress markers, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and thiobarbituric acid-reactive substances (TBARS), were measured in multiple organs, including the liver, intestine, brain, kidney, testis, lungs, pancreas, and heart. Histological examinations were conducted to assess tissue-level alterations. FFL exposure resulted in dose-dependent behavioral changes, hematological disturbances, and significant alterations in serum biochemical parameters. Antioxidant enzyme activities were reduced, while lipid peroxidation was increased across several organs, indicating enhanced oxidative stress. These findings were supported by histopathological changes consistent with organ injury. In conclusion, subacute oral exposure to FFL induced behavioral and multisystem toxicity in mice, largely mediated by oxidative stress mechanisms. These results highlight potential health risks associated with repeated FFL exposure and underscore the need for further toxicological evaluation.
