Subchronic Exposure Research Articles

Subchronic Chloroform Exposure Causes Intestinal Damage and Induces Gut Microbiota Disruption and Metabolic Dysregulation in Mice.

Chloroform is a prevalent toxic environmental pollutant in urban settings, posing risks to human health through exposure via various mediums such as air and tap water. The gut microbiota plays a pivotal role in maintaining host health. However, there is a paucity of research elucidating the impact of chloroform exposure on the gut microbiota. In this investigation, 18 SPF Kunming female mice were stratified into three groups (n = 6) and subjected to oral gavage with chloroform doses equivalent to 0, 50, and 150 mg/kg of body weight over 30 days. Our findings demonstrate that subchronic chloroform exposure significantly perturbs hematological parameters in mice and induces histopathological alterations in cecal tissues, consequently engendering marked disparities in the functional composition of cecal microbiota and metabolic equilibrium of cecal contents. Ultimately, our investigation revealed a statistically robust correlation, exhibiting a high degree of significance, between the intestinal microbiome composition and the metabolites that were differentially expressed consequent to chloroform exposure.

P24-01 Impact of perinatal and subchronic dietary glyphosate exposure on gut microbiota and liver metabolism in mice

P24-01 Impact of perinatal and subchronic dietary glyphosate exposure on gut microbiota and liver metabolism in mice

Co-exposure to multiple heavy metals and metalloid induces dose dependent modulation in antioxidative, inflammatory, DNA damage and apoptic pathways progressing to renal dysfunction in mice

Humans are exposed to a cocktail of heavy metal toxicants at the same time in the environment rather than single metal. The kidney is often a site of early damage due to high renal contact to these pollutants. This study was done to examine the cumulative toxic effect of multiple elements prevalent in the environment. To explore the effect of subchronic exposure to heavy metal mixture male and female Swiss albino mice were randomly divided into 14 groups and given varying doses [MPL (maximum permissible limit), 1X, 5X, 10X, 50X, or 100X] of the multiple metals and metalloid mixtures via drinking water for 8 weeks. It was determined that metal treatment caused increased metal load in renal tissue. The kidney function deteriorated in response to 10X, 50X, 100X concentration of the dosing mixture was found associated to oxidative stress, glomerular damage, necrosis, cell death and further exacerbation of the inflammation.

Effects of Head-Only Exposure to 900 MHz GSM Electromagnetic Fields in Rats: Changes in Neuronal Activity as Revealed by c-Fos Imaging without Concomitant Cognitive Impairments.

Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here.

Aggravated dyslipidemia in diabetic albino rats after subchronic oral aluminium chloride exposure

Aggravated dyslipidemia in diabetic albino rats after subchronic oral aluminium chloride exposure

Hepatic and metabolic outcomes induced by sub-chronic exposure to polystyrene microplastics in mice.

Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6weeks, received an oral administration of 0.3mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5µm (submicron) and 5µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity.

Matrine Suppresses Arsenic-Induced Malignant Transformation of SV-HUC-1 Cells via NOX2.

Arsenic (As) has been classified as a carcinogen for humans. There is abundant evidence indicating that arsenic increases the risk of bladder cancer among human populations. However, the underlying mechanisms have yet to be fully understood and elucidated. NADPH oxidases (NOXs) are the main enzymes for ROS production in the body. NADPH Oxidase 2 (NOX2), which is the most distinctive and ubiquitously expressed subunit of NOXs, can promote the formation and development of tumors. The utilization of NOX2 as a therapeutic target has been proposed to modulate diseases resulting from the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Matrine has been reported to exhibit various pharmacological effects, including anti-inflammatory, antifibrotic, antitumor, and analgesic properties. However, it has not been reported whether matrine can inhibit malignant transformation induced by arsenic in uroepithelial cells through NOX2. We have conducted a series of experiments using both a sub-chronic NaAsO2 exposure rat model and a long-term NaAsO2 exposure cell model. Our findings indicate that arsenic significantly increases cell proliferation, migration, and angiogenesis in vivo and in vitro. Arsenic exposure resulted in an upregulation of reactive oxygen species (ROS), NOX2, and NLRP3 inflammasome expression. Remarkably, both in vivo and in vitro, the administration of matrine demonstrated a significant improvement in the detrimental impact of arsenic on bladder epithelial cells. This was evidenced by the downregulation of proliferation, migration, and angiogenesis, as well as the expression of the NOX2 and NLRP3 inflammasomes. Collectively, these findings indicate that matrine possesses the ability to reduce NOX2 levels and inhibit the transformation of bladder epithelial cells.

Impacts of tolylfluanid on implantation and placental development: Disruption of mitochondrial function and implantation-related gene expression in vitro and in vivo

Tolylfluanid is a widely used pesticide and antifouling agent in agricultural and marine industries and is recognized as a potential endocrine disruptor. However, the toxicological effects of tolylfluanid on the placenta development was not elucidated. This study used trophoblastic cell (HTR-8/SVneo cell) and endometrial cell (T HESCs) lines as in vitro model and mouse models as in vivo model to investigate the toxic effects of tolylfluanid on implantation-associated cell and placenta development during early pregnancy. Experimental results indicated that both cell lines exhibited reduced viability upon tolylfluanid exposure. Various in vitro experiments were conducted at <1 mg/L concentration. The results indicate that tolylfluanid can arrest cell cycle and induce apoptosis in endometrial and trophoblastic cells, abnormally regulate Ca2+ homeostasis and MAPK signaling pathways, and disrupt mitochondrial function. In vivo experiments, subchronic tolylfluanid exposure to mouse during puberty and pregnancy period impaired placenta development, resulting in reduced fetal and placental weight, abnormal placental structures, and altered gene expression. Specifically, a decrease in the ratio of labyrinth/junctional zones and changes in placenta gene expression patterns after tolylfluanid exposure were similar to characters of adverse pregnancy outcomes such as preeclampsia and fetal growth restriction (FGR). This study suggests that tolylfluanid exposure may have negative outcomes on female reproduction, and highlights the need for stricter regulation and monitoring of tolylfluanid use to protect women's reproductive health. This is the first study indicating the adverse effects of tolylfluanid on implantation and placental development during pregnancy.

Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized CHRNA6 3'-UTR SNP (rs2304297) adolescent rats.

Introduction: The rewarding effects of drugs of abuse are associated with the dopaminergic system in the limbic circuitry. Nicotine exposure during adolescence is linked to increased use of drugs of abuse with nicotine and methamphetamine (METH) commonly used together. Nicotine acts on neuronal nicotinic acetylcholine receptor (nAChR) systems, critical for reward processing and drug reinforcement, while METH leads to a higher dopamine (DA) efflux in brain reward regions. A human single nucleotide polymorphism (SNP) in the 3'-untranslated region (UTR) of the α6 nicotinic receptor subunit gene (CHRNA6, rs2304297), has been linked with tobacco/nicotine and general substance use during adolescence. Using CRISPR-Cas9 genomic engineering, our lab recapitulated the CHRNA6 3'UTRC123G SNP, generating α6CC and α6GG allele carriers in Sprague Dawley rats. We hypothesized the CHRNA6 3'UTRC123G SNP would sex- and genotype-dependently enhance nicotine-induced METH self-administration as well as nicotine-induced DA overflow in the nucleus accumbens shell of adolescent α6GG and α6CC carriers. Methods: Adolescent male and female rats underwent a 4-day sub-chronic, low-dose (0.03mg/kg/0.1mL, x2) nicotine pretreatment paradigm to assess intravenous METH (0.02mg/kg/0.1mL) self-administration as well as nicotine- and METH (0.02mg/kg/0.1mL)-induced DA overflow in the nucleus accumbens shell (NAcS) using in vivo microdialysis coupled with high-performance liquid-chromatography-electrochemical detection (HPLC-ECD). Results: Nicotine pretreatment sex- and genotype-dependently enhanced subsequent METH self-administration in adolescent CHRNA6 3'UTRC123G SNP rats. Further nicotine and METH-induced DA overflow is observed in α6CC females as compared to α6GG females, with METH-induced DA overflow enhanced in α6GG males when compared to α6CC males. Conclusion: These findings demonstrate that the CHRNA6 3'-UTRC123G SNP can sex- and genotype-dependently impact adolescent nicotine-induced effects on METH self-administration and stimulant-induced DA overflow in reward regions of the brain.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6J male mice were subjected to a diet containing ATHC for 12weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

Curcumin Treatment Ameliorates Hepatic Insulin Resistance Induced by Sub-chronic Oral Exposure to Cadmium LOAEL Dose via NF-κB and Nrf2 Pathways.

Cadmium (Cd) is a global pollutant, and its accumulation in the liver causes oxidative stress, inflammation, insulin resistance (IR), and metabolic complications. This study investigated whether curcumin treatment could alleviate hepatic IR in Wistar rats exposed to sub-chronic cadmium and explored the underlying molecular pathways. Male Wistar rats were divided into a control group (standard normocaloric diet + cadmium-free water) and a cadmium group (standard normocaloric diet + drinking water with 32.5ppm CdCl2) for 30days. Oral glucose tolerance, insulin response, and IR were assessed using mathematical models. Liver tissue was analyzed for markers of oxidative stress, inflammation, and key regulatory pathways, including NF-κB, Nrf2, MAPKs (JNK and p38), and the IRS1-Akt pathway. We established an effective curcumin dose of 250mg/kg for 5days orally. Results demonstrated that after 30days of exposure, cadmium accumulated in the liver, inducing an oxidative and inflammatory state. This was characterized by increased expression of NF-κB, JNK, and p38, along with diminished Nrf2 expression, hepatic IR, hyperglycemia, and hyperinsulinemia. Curcumin treatment effectively alleviated these metabolic disorders by restoring the balance between NF-κB and Nrf2 in the liver, modulating the MAPK pathway, and, consequently, improving oxidative and inflammatory balance. In conclusion, this study suggests that cadmium induces hepatic IR through an imbalance between NF-κB and Nrf2 signaling pathways. Curcumin treatment appears to improve these pathways, thereby ameliorating hepatic IR.

Early exposure to glyphosate during larval development induces late behavioural effects on adult honey bees

As the most abundant pollinator insect in crops, Apis mellifera is a sentinel species of the pollinator communities. In these ecosystems, honey bees of different ages and developmental stages are exposed to diverse agrochemicals. However, most toxicological studies analyse the immediate effects during exposure. Late effects during adulthood after early exposure to pollutants during larval development are poorly studied in bees. The herbicide glyphosate (GLY) is the most applied pesticide worldwide. GLY has been detected in honey and beebread from hives near treated crops. Alterations in growth, morphogenesis or organogenesis during pre-imaginal development could induce late adverse effects after the emergence. Previous studies have demonstrated that GLY alters honey bee development, immediately affecting survival, growth and metabolism, followed by late teratogenic effects. The present study aims to determine the late impact on the behaviour and physiology of adult bees after pre-imaginal exposure to GLY. For that, we reared brood in vitro or in the hive with sub-chronic exposure to the herbicide with the average detected concentration in hives. Then, all newly emerged bees were reared in an incubator until maturity and tested when they became nurse-aged bees. Three behavioural responses were assessed as markers of cognitive and physiological impairment. Our results show i) decreased sensitivity to sucrose regardless of the rearing procedure, ii) increased choice latency and locomotor alterations during chemotaxis and iii) impaired associative learning. These late toxicity signs could indicate adverse effects on task performance and colony efficiency.

Sub-chronically exposing zebrafish to environmental levels of methomyl induces dysbiosis and dysfunction of the gut microbiota

The widespread use of carbamate pesticides has led to numerous environmental and health concerns, including water contamination and perturbation of endocrine homeostasis among organisms. However, there remains a paucity of research elucidating the specific effects of methomyl on gut microbial composition and physiological functions. This study aimed to investigate the intricate relationship between changes in zebrafish bacterial communities and intestinal function after 56 days of sub-chronic methomyl exposure at environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings reveal significant methomyl-induced morphological changes in zebrafish intestines, characterized by villi shortening and breakage. Notably, methomyl exposure down-regulated nutrient and energy metabolism, and drug metabolism at 0.05−0.10 mg/L, while up-regulating cortisol, inflammation-related genes, and apoptotic markers at 0.20 mg/L. These manifestations indicate physiological stress imposition and disruption of gut microbiota equilibrium, impacting metabolic processes and instigating low-grade inflammatory responses and apoptotic cascades. Importantly, changes in intestinal function significantly correlated with shifts in specific bacterial taxa abundance, including Shewanella, Rubrobacter, Acinetobacter, Bacillus, Luteolibacter, Nocardia, Defluviimonas, and Bacteroides genus. In summary, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms, emphasizing the necessity for further research to mitigate its repercussions on environmental health and ecosystem stability.

Sub-Chronic Methomyl Exposure Induces Oxidative Stress and Inflammatory Responses in Zebrafish with Higher Female Susceptibility.

The widespread use of carbamate pesticides has raised significant environmental and health concerns, particularly regarding water contamination and the disruption of defense systems in organisms. Despite these concerns, research on the differential impacts of pesticides on male and female organisms remains limited. This study focused on methomyl, investigating sex-specific differences in liver antioxidant defenses and inflammatory response indices in male and female zebrafish after 56 days of exposure to environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings indicate that methomyl exposure significantly increased ROS content in zebrafish livers, inducing oxidative stress and activating enzymatic antioxidant defenses such as SOD, CAT, and GSH-Px activities. Sub-chronic exposure altered the expression of apoptosis-related genes (Bax/Bcl2a and Caspases3a), resulting in liver cell apoptosis in a concentration-dependent manner, with the 0.20 mg/L concentration causing the most severe damage. Additionally, methomyl exposure at environmentally relevant concentrations triggered persistent inflammatory responses in liver tissues, evidenced by increased transcription levels of inflammatory factor genes and the activation of toll-like receptors, heightening susceptibility to exogenous allergens. It is noteworthy that oxidative damage indicators (AST, ROS, MDA) and inflammatory gene expressions (IL-1β, TNF-α) were significantly higher in female livers compared to male livers at 0.10-0.20 mg/L methomyl exposure. Consequently, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms and highlights the need for heightened consideration of the risks posed by environmental endocrine disruptors to female health and safety.

A 90-day subchronic exposure to heated tobacco product aerosol caused differences in intestinal inflammation and microbiome dysregulation in rats.

Smoking is one of the most important predisposing factors of intestinal inflammatory diseases. Heated tobacco product (HTP) is a novel tobacco category that is claimed to deliver reduced chemicals to human those reported in combustible cigarette smoke (CS). However, the effect of HTP on intestine is still unknown. In the framework of Organization for Economic Co-operation and Development guidelines 413 guidelines, Sprague-Dawley rats were exposed to HTP aerosol and CS for 13 weeks. The atmosphere was characterized and oxidative stress and inflammation of intestine were investigated after exposure. Furthermore, the faeces we performed with 16S sequencing and metabolomics analysis. HTP aerosol and CS led to obvious intestinal damage evidenced by increased intestinal pro-inflammatory cytokines and oxidative stress in male and female rats After HTP and CS exposure, the abundance that obviously changed were Lactobacillus and Turiciacter in male rats and Lactobacillus and Prevotella in female rats. HTP mainly induced the metabolism of amino acids and fatty acyls such as short-chain fatty acids and tryptophan, while CS involved into the main metabolism of bile acids, especially indole and derivatives. Although different metabolic pathways in the gut mediated by HTP and CS, both to inflammation and oxidative stress were ultimately induced. HTP aerosol and CS induced intestinal damage mediated by different gut microbiota and metabolites, while both lead to inflammation and oxidative stress. The concentration of various harmful components in heated tobacco product aerosol is reported lower than that of traditional cigarette smoke, however, its health risk impact on consumers remains to be studied. Our research findings indicate that heated tobacco product and cigarette smoke inhalation induced intestinal damage through different metabolic pathways mediated by gut microbiome, indicating the health risk of heated tobacco product in intestine.

Neurotoxicity of hexaconazole on rat brain: The aspect of biological rhythm

Hexaconazole is a widely used and frequently detected fungicide which is also reported to be persistent in environment. The toxicity of Hex to non-organisms such as reproductive toxicity, endocrine disrupting toxicity, and carcinogenic toxicity had been reported. However, study on the Hex-induced neurotoxicity is rare and the mechanism is still unclear. Therefore, in this study, environmental related concentrations of Hex were chosen to investigate the effects of Hex on nervous system from the aspect of biological rhythm under 90 d sub-chronic exposure. The results showed that Hex significantly affected the cognitive function of rats resulting in the deterioration of learning and memory ability and induced oxidative stress in rat brain. Moreover, the notable changes of neurotransmitters in rat brain suggested the disorder of nerve signaling conduction induced by Hex. The influence of Hex on biological rhythm was further detected which showed that levels of rhythm regulatory genes and proteins significantly disturbed at four monitored time periods. Based on these results, it was supposed that the underlying mechanism of Hex-induced cognitive dysfunction might through oxidative stress pathway. Our findings could systematically and comprehensively clarify the effects of Hex on nervous system and were helpful for prevention neurological diseases induced by triazole pesticides.

Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Effect of fluoride-induced testicular alteration in rats fed a high-fat diet.

Previous research on the well-known environmental pollutant fluoride has demonstrated that fluoride exposure can lead to oxidative stress-related male infertility. Obesity is another public health issue that has a detrimental impact on male fertility. Previously, findings on fluoride toxicity in high-fat diet (HFD) conditions associated with oxidative stress have been evidenced. This study aimed to evaluate the impact of subchronic fluoride exposure (5 mg/kg) plus a HFD on testicular alteration in Wistar rats. Animals were divided into four groups (control, HFD, fluoride, and fluoride 5 mg/kg plus HFD). The HFD contained a 50% kcal increase in fat (saturated fat), after 90 days of co-exposure to fluoride plus HFD, the animals showed a significant decrease in the adiposity index. The co-exposed group showed oxidative damage assessed through decreased glutathione (GSH) concentration (p < 0.0001), increased concentrations of malondialdehyde (MDA) (p < 0.0001), and the oxidation of proteins (p < 0.0001) vs the control group. Finally, testicular histology exhibited a reduction in spermatogonia and spermatocytes. The results of the study indicate that under these conditions, subchronic co-exposure to fluoride under HFD conditions could protect against the accumulation of epididymal fat, however, oxidative alteration at the testicular level is maintained.

Subchronic particulate matter exposure underlying polyhexamethylene guanidine phosphate–induced lung injury: Quantitative and qualitative evaluation with chest computed tomography

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Impact of sub chronic administration of deltamethrin on autoimmune activity in rat

Deltamethrin (DLM) is a newer kind of insecticide that is used on pets, livestock, and crops, as well as to combat malaria vectors and household pests. It belongs to the synthetic pyrethroid group and is being promoted as an alternative to organophosphate chemicals due to its persistent and destructive effects. The current study aimed to evaluate the impact of sub-chronic oral exposure to DLM on autoimmune activity in rats. Three groups of male albino rats (15 rats/group) including the control group, the ethanol-treated group (1 ml/rat), and the DLM-treated group (5 mg/kg b.w). Samples of blood were taken from all groups at 4-, 8- and 12-week intervals for the determination of hematological, cytokines, and immunological parameters. T lymphocyte subsets and Treg lymphocytes were determined in serum using flow cytometric acquisition. The results revealed that DLM significantly increased TNF-α, IL-33, IL-6, IL-17, IgG, IgM, WBCs, differential count, and platelets while decreasing Hb concentration and RBCs. Additionally, DLM decreased the number of T-cell subsets (CD3, CD4, CD5, and CD8) and Treg lymphocytes. All of these impacts became more severe over time. It is possible to conclude that the sub-chronic oral exposure to DLM disturbed autoimmune activity through the disturbances in immunological indices, CDs subset Treg lymphocytes.