Subacute Exposure Research Articles

Ascorbic Acid Mediated Amelioration of Bridelia micrantha Induced Alterations in Haematological, Histological and Proximate Composition of the Carcass of African Catfish, Clarias gariepinus (Burchell, 1822)

Acute and sub-acute exposure of piscicidal plant Bridelia micrantha (BM) during fishing of Sharptooth Catfish Clarias gariepinus juvenile causes alterations in haematological, histological and the carcass analysis. The result of water quality shows the normal value for fish culture in the tropics, the DO2 level of the water varies slightly such that the T1 , T2 , T3, T5and T0 were in the normal range, conductivity followed by T2 whereas T1 had the least value for conductivity, which the mean differences were statistically not significant (p>0.05) among the individual treatments. There was severe alterations in haematology, of Clarias gariepinus exposed to Brandelia micrantha, at 0.00, 0.042, 0.084, 0.126, 0.168 and 0.21mg/l during 60days of exposure periods, blood analysis show a reduction in white blood cell (mg/l)), Haemoglobin, Red blood cell (mg/l) Haemoglobin (g/dl), Lymphocytes (mg/l), Mean cell volume (fl), Mean cell concentration, tissue analysis indicated an alterations in the gill, liver and kidney while tissue analysis reveals severe degeneration of the renal tissue with severe intra renal necrosis (TN) and inflammatory cell aggregate (IC) with tubular atrophy (TA) in some areas and carcass analysis show severe reduction in Moisture (M), Crude Protein (CP) (Mg/l), Crude Lipid (CL), Ash, Nitrogen Free Extract (NFE), and Energy (kcal/100g). The recovery of C. gariepinus from Bridelia micrantha (BM) was evaluated by exposing C. gariepinus to a 60-days depuration, on ascorbic acid (AA) supplemented diet at concentrations of 0.00, 25, 50, 75, 100, 125ml/l. After 60-days depuration some of the lesions in histological, haematological and proximate composition of the carcass attained different stages of recovery as compared to the control.

Gastrointestinal toxicity following sub-acute exposure of erythrosine in rats: biochemical, oxidative stress, DNA damage and histopathological studies.

Erythrosine, a synthetic food dye, has been controversial due to its potential health risks. This study examines the effect of erythrosine on activity of antioxidative enzymes, oxidative stress indices, DNA damage through comet assay, and histopathological changes on stomach, intestine, and colon over a period of 28 days in rats. Twenty-four rats were randomly divided into four groups (n = 6). The first is the control group and then one each for three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). The results revealed that with increasing dosages the activity of catalase decreased in stomach and intestine but in colon, the catalase activity increased. Superoxide dismutase and glutathione-S-transferase activity decreased in dose-dependent manner in all three tissues. While, in stomach and intestine, the acetylcholinesterase activity showed increment in ¼ ADI dose group and then declined in ½ ADI and ADI dose-administered rats. The oxidative stress indicators showed elevated levels of lipid peroxidation, hydrogen peroxide concentration, and lactate dehydrogenase activity suggesting heightened free radical activity and potential oxidative damage. The comet test was used to evaluate DNA damage, revealing substantial damage in the erythrosine administered groups. Histopathological examination showed inflammatory infiltration and other degenerative changes in gastrointestinal tract, highlighting the dye's adverse effects. The research underscores the need for a comprehensive reevaluation of the safety and toxicity of food dyes like erythrosine, especially considering the inconsistencies in existing studies regarding the dye's safety.

Gene expression changes in mouse lung induced by subacute inhalation of PM10-rich particulate matter

Introduction Particulate matter (PM) air pollution is associated with an increased incidence of lung diseases, but the underlying mechanisms have not been fully elucidated. In this study, a mouse model of subacute lung inflammation was employed to investigate the cellular responses and gene expression changes induced by exposure to natural ambient air pollution. Methods C57BL/6J mice were exposed to road dust (primarily PM10) at 150 µg/m³ for 21 days (8 h/day) through a nose-only inhalation exposure system. Lung tissues were analyzed for the expression of proinflammatory signaling, oxidative stress, and fibrosis markers. RNA-sequencing analysis was conducted to identify differentially expressed genes (DEGs). A gene ontology over-representation analysis was performed to identify the altered genetic pathways. Results Elevated levels of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and an increase in phosphorylated MAPK were determined in the road dust exposure group compared to the control group. Histopathological examinations revealed more severe lung inflammation and damage in the exposed mice, including fibrosis and bronchiolar hyperplasia. Gene expression profiling identified 108 DEGs, with decreases in most except genes such as Krt15 and Reg3g. The protein–protein interaction network analysis together with text-mining identified 18 key hub genes, associated with fatty acid oxidation, lipid metabolism, and peroxisomes. Conclusion This study identified key genes, signaling pathways, and cellular responses in mouse lung affected by road dust exposure. These findings contribute to a deeper understanding of the transcriptional and cellular responses induced by subacute exposure to the PM in road dust.

Sub-acute Inhalation Exposure to Aluminum Oxide Nanoparticles and its Effects on Wistar Rats as Opposed to the Micro-sized Chemical Analog.

Aluminum oxide nanoparticles (Al2O3 NPs) are widely used in various productions. Simultaneously, many research works report the toxic effects of this nanomaterial. Given that, there is a growing risk of negative effects produced by Al2O3 NPs on public health. This study aims to investigate the toxic effects of Al2O3 NPs as opposed to the micro-sized chemical analogue under sub-acute inhalation exposure. We identified the physical properties of Al2O3 NPs as opposed to the micro- sized chemical analogue, including size, specific surface area, and total pore volume. Inhalation exposure to Al2O3 NPs was simulated on Wistar rats in a chamber for whole-body. The animals were exposed for 4 hours each day for 28 days. NPs and MPs concentrations in the chamber were kept at ~ 1/4000 from LC50. Rats' behavior was examined prior to the exposure period and after it; after the last daily exposure, we examined biochemical and hematological blood indicators, NPs and MPs bioaccumulation, and pathomorphological changes in organ tissues. The tested Al2O3 sample is a nanomaterial according to its analyzed physical properties. Rats' behavior changed more apparently under exposure to NPs compared to MPs. Aluminum levels, which were 1.62-55.20 times higher than the control, were identified in the lungs, liver, brain, and blood under exposure to NPs. These levels were also 1.55-7.65 times higher than the control under exposure to MPs. Biochemical indicators of rats' blood also changed under exposure to NPs against the control. We identified more active ALT, AST, ALP, and LDH, elevated levels of GABA, MDA, and conjugated bilirubin, and a lower level of Glu. As opposed to exposure to MPs, ALT, AST, and ALP were more active; GABA and MDA levels were higher; Glu level was lower. Under exposure to NPs, the number of platelets grew, whereas no similar effect occurred under exposure to MPs. We established pathomorphological changes in tissues of the lungs, brain, heart, and liver under exposure to Al2O3 NPs; similar changes occurred only in the lungs under exposure to MPs. Exposure to NPs induced changes in tissue structures in a wider range of various organs, and these changes were more apparent than under exposure to MPs. Greater toxicity of Al2O3 NPs as opposed to MPs is evidenced by a wider range of organs where their bioaccumulation occurs, more apparent pathomorphological and pathological functional changes. Established peculiarities of toxic effects produced by the analyzed nanomaterial should be considered when developing hygienic recommendations aimed at preventing and mitigating adverse impacts of Al2O3 NPs on human health under inhalation exposure.

Ferroptosis involvement in the neurotoxicity of flunitrazepam in zebrafish

The occurrence of psychoactive drugs such as benzodiazepines (BZDs) has been frequently observed in water environments, however, there is still limited understanding regarding their potential impact on neurological health and underlying mechanisms. This study evaluates the neurotoxicity of the typical BZD drug flunitrazepam (FLZ, 0.2 and 5 μg/L) in zebrafish embryos and adults, and investigates the relationship between ferroptosis and FLZ-induced neurotoxicity. The results indicate that acute exposure to FLZ significantly inhibits zebrafish embryo hatching and promotes death, induces larval deformities, and leads to abnormal neurobehavioral responses in larvae, likely due to ferroptosis induction. Results from a 30-day subacute exposure to FLZ show that it decreases motor function and induces cognitive impairment in adult zebrafish. Immunofluorescence of brain tissues revealed a reduction in neurons in the telencephalon and an increase in microglia in the mesencephalon of the zebrafish exposed to FLZ. The ultrastructure of brain mitochondria showed serious damage. Besides, FLZ exposure increased iron levels, reduced GSH/GSSG and increased LPO in brain tissue, which is related to the abnormal expression of genes associated with ferroptosis. In the rescue experiments with co-exposure to deferoxamine (DFO), the motor-related parameters and biochemical indexes related to ferroptosis were restored, suggesting that FLZ can induce ferroptosis. The molecular docking results indicated that FLZ had a higher affinity with transferrin. This study elucidates the close relationship between ferroptosis and FLZ-induced neurotoxicity, which is significant for understanding the physiological damage caused by psychoactive substances and assessing environmental risks.

The Effect of Sub-Acute Inhalation Exposure to Polyethylene and Polyvinyl Chloride Micro-Nano Plastics on the Superoxide Dismutase (SOD) Level and Malondialdehyde (MDA) Level in Rat Ovary

Plastic is a synthetic or semi-synthetic organic polymer that is widely used in daily life and in industrial production. Microplastics are widespread contaminants and can enter the human body through the consumption of foods containing microplastics, inhalation of microplastics in the air, and skin contact with microplastic particles present in products. Microplastics can enter the ovaries as foreign bodies and can cause inflammation, oxidative stress, and even ovarian granulosa cell death. Polyethylene plastic shards generally have a higher ability to absorb environmental toxins than other types of plastic. Polyvinyl chloride (PVC) is one of the oldest thermoplastic polymers that is often used as water pipes. PVC has carcinogenic monomers and some harmful additives. This study aims to determine the effect of subacute exposure to micro-nanoplastics per inhalation on SOD and MDA levels in rat ovaries. The research method used is a true experimental design with a Randomize Post Test Only Group Design research design. This study used the ovarian organs of female white rats that had been exposed to PVC and PE for 28 days. The number of samples used in this study amounted to 18 female rats. Subacute exposure to micro-nanoplastics per inhalation can lower SOD levels and significantly increase MDA levels in rat ovaries. This study is expected to provide knowledge and an overview for future research on the mechanism of toxicity of micro-nanoplastic exposure that has an impact on female infertility through free radicals in the ovaries.

Lack of cell proliferation activity in gastrointestinal organs in a subacute oral exposure of known tumor promoters in rats

Lack of cell proliferation activity in gastrointestinal organs in a subacute oral exposure of known tumor promoters in rats

Hepatotoxicity induced by subacute exposure of Mancozeb and Arsenic in Wistar rats: Mitigating effect of quercetin and catechin

BackgroundWidespread use of Mancozeb (MZ) fungicide in endemic areas having high levels of arsenic (As+3) in the groundwater is likely to cause toxicosis in humans and animals. Therefore, the present study aimed to determine the hepatotoxic effect of MZ and As+3 interaction in Wistar rats and mitigating potential of quercetin and catechin on such toxicity. MethodsSixty adult rats were randomly divided into 10 groups of 6 animals each. Group I served as control and group II was exposed to MZ (800 mg kg-1, PO). Groups III, IV, and V were provided drinking water containing As+3 at the rate of 10, 50 and 100 µg L-1, respectively. Groups VI, VII, and VIII were given drinking water containing As+3 at 10, 50 and 100 µg L-1, respectively, along with MZ. Groups IX and X received drinking water contaminated with 100 µg L-1, As+3 and MZ along with quercetin or catechin (50 mg kg-1 each), respectively. ResultsSignificant (p <0.05) alterations in hepatic biomarkers in blood, liver antioxidant status and hepatic histoarchitecture were observed in animals treated with individual toxicants in a dose-dependent manner, however, such toxicity-induced changes were more severe in co-exposed rats. The administration of quercetin or catechin significantly mitigated the dual toxicant administration-driven changes in biochemical markers of hepatic damage, hepatic antioxidant profile and liver histomorphology. ConclusionsBoth quercetin and catechin proved beneficial in reducing toxicant-induced oxidation-mediated hepatic damage as demonstrated by alleviation in altered levels of determinants of hepatic biochemical and oxidative stress parameters in addition to restoration of toxicant-induced histological alterations of hepatic tissue.

Sub-acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice.

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.

Pulmonary Protective Effects of Vitamin D and N-Acetylcysteine on Paraquat-Induced Lung Toxicity in Rats: Modulation of Oxidant / Antioxidant Balance

Background: Paraquat (PQ) is one of the most common herbicides used in agriculture that can lead to very acute toxicity in mammals. It has been reported that PQ has destructive effects on the lungs. Objective: We aimed to investigate the effect of N-acetyl Cysteine (NAC) and Vitamin D (Vit D) on the oxidative toxicity of the lung in subacute paraquat exposure. 36 male albino Wistar rats at 8 weeks were randomly divided into 6 groups (n=6). A control group, a PQ-intoxicated group (5 mg/kg body weight), a Vit D-treated group (2 μg/kg), an NAC-treated group, a PQ (6.25 mg/kg) + Vit D group, and finally a PQ + NAC group, each was treated for 7 days. Methods: In this experimental study, Lipid Peroxidation (LPO), Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), Total Thiol Groups (TTG), and Hydroxyproline (Hyp) levels in lung tissue were evaluated. Results: PQ exposure resulted in a substantial elevation of LPO, TOS, and Hyp levels. Conversely, TAC and TTG content demonstrably declined. Administration of either PQ+Vit D or PQ+NAC significantly reduced LPO, TOS, and Hyp levels in the PQ-exposed rats compared to the PQ group alone. Conversely, TAC and TTG content significantly increased in these groups. These findings suggest that both vitamin D and NAC may function as free radical scavengers and potential antioxidant agents, potentially alleviating the detrimental effects of PQ poisoning on the lungs. Conclusion: The present study has demonstrated the administration of Vit D and NAC to significantly mitigate PQ-induced lung injury in rats. This protective effect can be likely attributed to their modulation of the oxidant/antioxidant balance, as evidenced by reductions in LPO, TOS, and Hyp levels, alongside increases in TAC and TTG content. These findings suggest that vitamin D and NAC may function as free radical scavengers and antioxidant enhancers, offering protection against PQ-induced oxidative stress and subsequent lung tissue damage.

Spatial regulation of NMN supplementation on brain lipid metabolism upon subacute and sub-chronic PM exposure in C57BL/6 mice

BackgroundAtmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed.ResultsIn this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis.ConclusionsThis study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Integrated Biomarker Response Emphasizing Neuronal Oxidative Stress and Genotoxicity Induced by Oxamyl in Sprague Dawley Rats: Ameliorative Effect of Ginseng as a Neuroprotective Agent.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

P25-22 Insight into the cardiotoxicity in Wistar rats after subacute exposure to a mixture of lead and polychlorinated-biphenyls

P25-22 Insight into the cardiotoxicity in Wistar rats after subacute exposure to a mixture of lead and polychlorinated-biphenyls

Immunomodulation Induced in BALB/c Mice after Subacute Exposure to Hydroalcoholic Extract of Artimisia Dracunculus.

Tarragon, with the scientific name of Artemisia dracunculus, is a perennial herbaceous plant with a wide spectrum of pharmacologic properties. In the current investigation, BALB/c mice were used to examine the immunomodulatory effects of hydroalcoholic extract of tarragon (HET). Mice were treated with hydroalcoholic extract of Artimisia dracunculus (HET) at two doses (250 and 500 mg/kg) for 14 days. The host hematological parameters, spleen cellularity histopathology, hemagglutination titer assay (HA), delayed-type hypersensitivity (DTH) responses, IFN-γ and IL-4 levels produced by spelenocytes, and the proliferation of lymphocytes were assayed. HET at a high dose significantly could increase the number of white blood cells and lymphocytes compared to the control group. The lymphocyte proliferation in exposure to PHA significantly increased in the HET group at both doses compared to the control group, whilst this index in the presence of LPS increased significantly for the 500 mg/kg-HET group only. Moreover, in the HA and DTH tests, HET significantly increased the proliferation of lymphocytes as compared with the control group. Furthermore, HET significantly increased the amount of IFN-γ parallel to a decrease in the level of IL-4 in compared to the control group. Based on our findings, HET has potent immunostimulant characteristics. More investigation into tarragon's potential to be used in the treatment of disorders caused by a weakened immune response should be conducted.

Biotransformation, Bioaccumulation, and Bioelimination of Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate In Vivo.

Aryl phosphorus flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), are widely used worldwide. Understanding the fates of aryl-PFRs in vivo is crucial to assessing their toxicity and the risks they pose. Seven TPHP metabolites, including Phase I hydrolysis and hydroxylation and Phase II glucuronidation products, were identified in C57BL/6J male mice following subacute dietary exposure to aryl-PFRs (70 μg/kg body weight (bw)/day) for 7 days. TPHP was almost completely metabolized by mice (∼97%), with DPHP the major metabolite formed (34%-58%). In addition, mice were exposed to aryl-PFRs (7 μg/kg bw/day) for 12 weeks. Both TPHP and DPHP occurred at higher concentrations in the digestive tract (intestine and stomach), liver and heart. The total concentration of DPHP in all organs was 3.55-fold greater than that of TPHP. Recovery analysis showed that the rate of TPHP elimination from mouse organs reached 38%, while only 3%-5% of DPHP was removed, suggesting that the rates of degradation and elimination of DPHP were slower than TPHP and its bioaccumulation potential was higher. These results highlight the critical role of DPHP in the biotransformation, bioaccumulation, and bioelimination of TPHP, providing valuable insights into the fate of aryl-PFRs in vivo.

Correlation between Exposure to UFP and ACE/ACE2 Pathway: Looking for Possible Involvement in COVID-19 Pandemic.

The overlap between the geographic distribution of COVID-19 outbreaks and pollution levels confirmed a correlation between exposure to atmospheric particulate matter (PM) and the SARS-CoV-2 pandemic. The RAS system is essential in the pathogenesis of inflammatory diseases caused by pollution: the ACE/AngII/AT1 axis activates a pro-inflammatory pathway, which is counteracted by the ACE2/Ang(1-7)/MAS axis, which activates an anti-inflammatory and protective pathway. However, ACE2 is also known to act as a receptor through which SARS-CoV-2 enters host cells to replicate. Furthermore, in vivo systems have demonstrated that exposure to PM increases ACE2 expression. In this study, the effects of acute and sub-acute exposure to ultrafine particles (UFP), originating from different anthropogenic sources (DEP and BB), on the levels of ACE2, ACE, COX-2, HO-1, and iNOS in the lungs and other organs implicated in the pathogenesis of COVID-19 were analyzed in the in vivo BALB/c male mice model. Exposure to UFP alters the levels of ACE2 and/or ACE in all examined organs, and exposure to sub-acute DEP also results in the release of s-ACE2. Furthermore, as evidenced in this and our previous works, COX-2, HO-1, and iNOS levels also demonstrated organ-specific alterations. These proteins play a pivotal role in the UFP-induced inflammatory and oxidative stress responses, and their dysregulation is linked to the development of severe symptoms in individuals infected with SARS-CoV-2, suggesting a heightened vulnerability or a more severe clinical course of the disease. UFP and SARS-CoV-2 share common pathways; therefore, in a "risk stratification" concept, daily exposure to air pollution may significantly increase the likelihood of developing a severe form of COVID-19, explaining, at least in part, the greater lethality of the virus observed in highly polluted areas.

Subacute exposure to a mixture of tributyltin plus mercury impairs reproductive axis function, exacerbating premature ovarian insufficiency features and reducing fertility in female rats

Tributyltin (TBT) and mercury (Hg) are endocrine-disrupting chemicals that individually cause reproductive complications. However, the reproductive consequences of exposure to a mixture of TBT plus Hg are not well known. We hypothesized that exposure to a mixture of TBT plus Hg would alter hypothalamic-pituitary-gonadal (HPG) axis function. Female rats were exposed to this mixture daily for 15 days, after which chemical accumulation in the tissues, morphology, hormone levels, inflammation, fibrosis, and protein expression in the reproductive organs were assessed. Increases in tin (Sn) and Hg levels were detected in the serum, HPG axis, and uterus of TBT-Hg rats. TBT-Hg rats exhibited irregular estrous cycles. TBT-Hg rats showed an increase in gonadotropin-releasing hormone (GnRH) protein expression and follicle-stimulating hormone (FSH) levels and a reduction in luteinizing hormone (LH) levels. Reduced ovarian reserve, antral follicles, corpora lutea (CL) number, and estrogen levels and increased atretic and cystic follicles were found, suggesting that TBT-Hg exposure exacerbated premature ovarian insufficiency (POI) features. Furthermore, TBT-Hg rats exhibited increased ovarian mast cell numbers, expression of the inflammatory markers IL-6 and collagen deposition. Apoptosis and reduced gland number were observed in the uteri of TBT-Hg rats. A reduction in the number of pups/litter for 90 days was found in TBT-Hg rats, suggesting impaired fertility. Strong negative correlations were found between serum and ovarian Sn levels and ovarian Hg levels and ovarian reserve and CL number. Collectively, these data suggest that TBT plus Hg exposure leads to abnormalities in the HPG axis, exacerbating POI features and reducing fertility in female rats.

Effect of sub-acute exposure of metal-organic framework-199 on cognitive function and oxidative stress level of brain tissue in rat

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators’ expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1β were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.

Toxicological Assessment of Pesticide Exposure in Wistar Rats: An Acute and Sub-Acute Inhalation Study

Background: Pesticide ubiquity and extensive applications have attendant public health implications. This study examines the immediate and prolonged inhalation toxicity of various commonly used insecticides in male Wistar rats. Methods: 192 male Wistar rats were utilized and kept in regular housing. The study was carried out in three stages: a preliminary test, an acute test, and a sub-acute. Wistar rats, housed in an improvised chamber, were exposed to varying doses of insecticides in each phase to assess their toxicities to insecticides. For comparativeness, we withdrew 57 of the rats from exposure to ascertain possible recovery. The study included monitoring behavioral changes, recording mortality rates, and conducting necropsies to evaluate organ pathology. Dose-response relationships were analyzed to determine lethal doses (LD50) and potential sublethal effects. Results: Overall, we found a dose-related increase in the severity of the response, which potentially indicates an alteration of a specific biochemical process. The range-finding test assessed the effects of DD Force, Sniper, Industrial Camphor, Edible Camphor, Kerosene, and combined pesticides. It revealed significant physiological impacts followed by mortalities at specific dosage levels. Subsequent acute toxicity testing determined LC50 values for each insecticide. Rats showed a dose-dependent health deterioration following sub-acute exposure, particularly in the combined pesticide group, indicating synergistic toxicity. Conclusion: Exposure to the combined pesticide at high doses was associated with severe toxicities in the tested rats. This evidence suggests that commonly used pesticides could potentiate adverse health outcomes when results are extrapolated in humans.

Multi-omics integration identifies ferroptosis involved in black phosphorus quantum dots-induced renal injury

Black phosphorus quantum dots (BPQDs) have recently emerged as a highly promising contender in biomedical applications ranging from drug delivery systems to cancer therapy modalities. Nevertheless, the potential toxicity and its effects on human health need to be thoroughly investigated. In this study, we utilized multi-omics integrated approaches to explore the complex mechanisms of BPQDs-induced kidney injury. First, histological examination showed severe kidney injury in male mice after subacute exposure to 1 mg/kg BPQDs for 28 days. Subsequently, transcriptomic and metabolomic analyses of kidney tissues exposed to BPQDs identified differentially expressed genes and metabolites associated with ferroptosis, an emerging facet of regulated cell death. Our findings highlight the utility of the multi-omics integrated approach in predicting and elucidating potential toxicological outcomes of nanomaterials. Furthermore, our study provides a comprehensive understanding of the mechanisms driving BPQDs-induced kidney injury, underscoring the importance of recognizing ferroptosis as a potential toxic mechanism associated with BPQDs.