Toxicology Research最新文献

Background: Aflatoxin B1 (AFB1) food contamination is a global health hazard that has detrimental effects on both human and animal health. The objective of the current study is to assess the protective impact of carnosic acid against AFB1-induced toxicities in the liver, kidneys, and heart.

Methods: Forty male Wistar Albino rats (weighting 180 ~ 200 g) were allocated into 5 groups (8 rats each); the 1^st group received saline as served as a control, the 2^nd group received carnosic acid (CA100) at a dose of 100 mg/kg bw/day by gavage for 14 days, the 3^rd group received AFB1 at a dose of 2.5 mg/kg bw, orally twice on days 12 and 14, the 4^th group (AFB1-CA50) received AFB1 as in the 3^rd group and CA at a dose of 50 mg/kg bw/day, and the 5^th group (AFB1-CA100) received AFB1 as in the 3^rd group and CA as in the 2^nd group.

Results: CA significantly decreased the liver enzymes (ALT, AST. ALP), renal function products (LDH, BUN, creatinine), and cardiac enzymes (CK and CK-MB) to control levels after the high increment by AFB1 exposure. Moreover, CA significantly decreased the oxidative stress (MDA, NO, 8-OHdG) and increased the antioxidant enzyme activities (CAT, GSH, GSH-Px, and SOD) after severe disruption of oxidant/antioxidant balance by AFB1 exposure. Interestingly, CA significantly decreased the proinflammatory mediators (IL-6, IL-1β, and TNF-α) to the control levels after severe inflammation induced by AFB1 exposure.

Conclusions: Conclusively, CA had antioxidant, anti-inflammatory, and anti-DNA damage effects against hepatic, renal, and cardiac AFB1-induced toxicities.

Several anabolic androgenic steroids (ASSs) are a group of synthetic molecules derived from testosterone and developed mainly for veterinary use that classed as a Schedule III and sometimes utilized by athletes to enlarge their muscles. Abuse of anabolic androgenic steroids can result in severe organ damage that cannot be repaired. Therefore; the objective of the current investigation was to examine the therapeutic effects of vitamin B17 (VitB17) on the testicular toxicity caused by the anabolic steroid Trenorol in male rats. Rats were randomly assigned into control, VitB17 (50 mg/kg b.wt./day, orally), Trenorol (received 10 mg/kg b.wt./week, IM) and Trenorol + VitB17 treated groups. At the end of experiment, hormonal assay, semen evaluation, testicular enzymes, and DNA damage were assessed. Besides, the histopathological and immunohistochemical investigations of the P53 expression were performed. Current results revealed that; Trenorol induced significant depletion in relative weights of testis (RWT), total testosterone follicle stimulating hormone (FSH), and luteinizing hormone (LH), sperm count, morphology index, viability, progressive motility, and testicular injury and a significant increase sperm abnormalities, testicular DNA damage and P53 experssions. Treatment of rats with Trenorol + VitB17 decreased the testicular toxicity, sperm parameters, DNA damage and apoptosis. We can conclude that; Trenorol induced toxicity, DNA damage and apoptosis in rat testis and treatments with VitB1 improved these parameters.

Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored.

Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators.

Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro.

Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.

Because of their beneficial properties, natural products, especially medicinal plants, are becoming increasingly popular worldwide and play a significant role in research. This study was aimed to evaluate the nephroprotective effect of sinapic acid against mercuric chloride-induced renal toxicity in mice. The mice were allocated to four groups named a normal group (G1), model group (G2; received HgCl₂, 1 mg/kg bw), treatments groups (G3 and G4: received 50 and 100 mg/kg bw of sinapic acid together with HgCl2). Mice received HgCl₂ remarkably showed alteration in all examined biochemical biomarkers (urea, creatinine, and bilirubin), and induced alteration in blood cell picture and anemia. HgCl₂ intoxication decreased both systemic and renal antioxidant activity and induced over all oxidative stress as indicated by alteration in inflammation and oxidative stress associated markers. HgCl₂ affected renal histology with leukocytic and inflammatory cell infiltration, fibrosis and tubular necrosis. Administration of sinapic acid (50 and 100 mg/kg bw) markedly restored the HgCl_2-induced oxidative stress (serum and renal: MDA, GSH, CAT, SOD, and T-AOC), proinflammatory cytokines (serum and renal: TNF-α, IL-6, IL-1β, and PGE2) and restored the changes on biochemical markers, and hematological parameters (hemoglobin, erythrocytes, platelets, and leukocytes). Taken together, the results of the present study disclose that sinapic acid has the potential to attenuate HgCl₂-induced renal toxicity and may be an ideal choice against mercury poisoning.

Oxidative injury is concerned with the pathogenesis of several liver injuries, including those from acute liver failure to cirrhosis. This study was designed to explore the antioxidant activity of Bacopa monnieri (BM) on Aflatoxin B1 (AFB1) induced oxidative damage in Wistar albino rats. Aflatoxin B1 treatment (200 μg/kg/day, p.o.) for 28 days induced oxidative injury by a significant alteration in serum liver function test marker enzymes (AST, ALT, ALP, LDH, albumin and bilirubin), inflammatory cytokines (IL-6, IL-10 and TNF-α), thiobarbituric acid reactive substances (TBARS) along with reduction of antioxidant enzymes (GSH, SOD, CAT), GSH cycle enzymes and drug-metabolizing enzymes (AH and AND). Treatment of rats with B. monnieri (20, 30 and 40 mg/kg for 5 days, p.o.) after 28 days of AFB1 intoxication significantly restored these parameters near control in a dose-dependent way. Histopathological examination disclosed extensive hepatic injuries, characterized by cellular necrosis, infiltration, congestion and sinusoidal dilatation in the AFB1-treated group. Treatment with B. monnieri significantly reduced these toxic effects resulting from AFB1. B. monnieriper se group (40 mg/kg) did not show any significant change and proved safe. The cytotoxic activity of B. monnieri was also evaluated on HepG2 cells and showed a good percentage of cytotoxic activity. This finding suggests that B. monnieri protects the liver against oxidative damage caused by AFB1, which aids in the evaluation of the traditional usage of this medicinal plant.

The modified phytochemical derivative, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12), has been identified as a potential therapeutic platform based on its capacity to improve disease outcomes in models of neurodegeneration and cancer. However, comprehensive safety studies investigating pathology and off-target binding have not been conducted. To address this, we administered C-DIM12 orogastrically to outbred male CD-1 mice for 7 days (50 mg/kg/day, 200 mg/kg/day, and 300 mg/kg/day) and investigated changes in hematology, clinical chemistry, and whole-body tissue pathology. We also delivered a single dose of C-DIM12 (1 mg/kg, 5 mg/kg, 25 mg/kg, 100 mg/kg, 300 mg/kg, 1,000 mg/kg) orogastrically to male and female beagle dogs and investigated hematology and clinical chemistry, as well as plasma pharmacokinetics over 48-h. Consecutive in-vitro off-target binding through inhibition was performed with 10 μM C-DIM12 against 68 targets in tandem with predictive off-target structural binding capacity. These data show that the highest dose C-DIM12 administered in each species caused modest liver pathology in mouse and dog, whereas lower doses were unremarkable. Off-target screening and predictive modeling of C-DIM12 show inhibition of serine/threonine kinases, calcium signaling, G-protein coupled receptors, extracellular matrix degradation, and vascular and transcriptional regulation pathways. Collectively, these data demonstrate that low doses of C-DIM12 do not induce pathology and are capable of modulating targets relevant to neurodegeneration and cancer.

This investigation explores the various impacts that polystyrene microplastics (PS-MPs) have on human health. As most of the plastic materials affect human health when they release leachable toxic substances that affect human health, this causes a negative effect that determines poor health conditions and leads to health hazards associated with plastic toxins routed in the human body, such as: Polychlorinated Biphenyls, Polybrominated Biphenyls etc. The study includes micro-plastic exposure assessment on testicular structure analysis, and cytotoxicity evaluations of different human cell types. The findings clarified the possible dangers of PS-MPs exposure from food, medications, and common products, emphasising the necessity of standard specimen handling procedures for precise biomonitoring.

Aim: To explore the differential genes in Parkinson's disease (PD) through a preliminary GEO database, and to investigate the possible mechanisms.

Materials and methods: The PD differentially expressed genes (DEGs) were analyzed by the microarray method. Then, these DEGs were applied to KEGG and GO analyses to predict the related signaling pathways and molecular functions. Comparison of GRAMD1C expression levels in the putamen of normal and Parkinson's patients by bioinformatic analysis. PC12 cells were cultured to construct a 6-hydroxydopamine (6-OHDA)-induced Parkinson's cell model. RT-qPCR was performed to detect the efficiency of GRAMD1C siRNA. MTT assay was conducted to examine the proliferation of cells. Then, the apoptosis of each group of cells was measured by flow cytometry. Western blot was carried out to determine the expression of apoptosis-related proteins.

Results: Through bioinformatics, GRAMD1C was confirmed to be one of the most significantly upregulated genes in PD. Furthermore, GRAMD1C was notably enhanced in the PD patients and 6-OHDA-induced PC12 cells. Besides, 6-OHDA stimulation significantly reduced PC12 cell proliferation, and it reverted with the GRAMD1C siRNA. Moreover, the flow cytometry results showed that knockdown of GRAMD1C could effectively reduce the high apoptosis rate of PC12 cells induced by 6-OHDA treatment. Similarly, western blot results found that 6-OHDA stimulation markedly increased the expression levels of Bax and Caspase 3Caspase 3 and decreased the Bcl-2 expression in PC12 cells, and GRAMD1C knockdown reversed these changes.

Conclusion: GRAMD1C is upregulated in PD, and may affect the PD process through the apoptotic pathway.

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.

Aim: To explore the effect of Dexmedetomidine (DEX) on lung injury in patients undergoing One-lung ventilation (OLV).

Methods: Esophageal cancer patients undergoing general anesthesia with OLV were randomly divided into the DEX group and control group, with 30 cases in each group. Mean arterial pressure (MAP), heart rate (HR), arterial partial pressure of oxygen (PO2), and arterial partial pressure of nitrogen dioxide (PCO2) were recorded at the time points after anesthesia induction and before OLV (T1), OLV 30 min (T2), OLV 60 min (T3), OLV 120 min (T4), OLV end before (T5) and before leaving the room (T6) in both groups. Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was applied to detect the levels of CC16 mRNA. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CC16 protein levels. The content of malondialdehyde (MDA) in serum was determined by thio barbituric acid (TBA) method. ELISA was used to measure the concentrations of TNF-α (tumor necrosis factor-alpha)/and IL-6 (interleukin 6).

Results: DEX treatment slowed down HR at time points T1-T6 and increased PO2 and PCO2 at time points T2-T5 compared with the control group. Moreover, at time points T2-T6, DEX treatment reduced the levels of club cell secretory protein-16 (CC16) mRNA and serum CC16 protein levels. Furthermore, DEX treatment caused the reduction of MDA, TNF-α and IL-6 concentrations in serum of patients.

Conclusion: During the OLV process, DEX could reduce serum CC16 protein levels, inhibit inflammatory reactions and oxidative stress, and improve oxygenation index, indicating a protective effect on lung injury during OLV.