Drug and Chemical Toxicology最新文献

In the present study, phenolic and flavonoid composition and biological properties of methanolic extract of wild growing Paxillus involutus collected in Serbia have been investigated. Ellagic acid was the most abundant phenolic compound (34.92 µg g-¹), followed by 5-O-caffeoylquinic acid (4.51 µg g-¹), whereas isoorientin was the most abundant flavonoid (3.42 µg g-¹). P. involutus turned out to be a rich source of phenolic compounds (74.67 mg GAE g-¹ d.w.), whereas total flavonoid content was significantly lower (4.05 mg QE g-¹ d.w.). As for the various investigated biological activities, methanolic extract exerted high level of antioxidant, antimicrobial and antibiofilm activities. The highest antioxidative potential was measured by TAC (350 TE mg g-¹ d.w.), whereas evaluation of antimicrobial properties showed selective antimicrobial potential toward tested pathogenic microorganisms, with resistant strain of E. coli being the most susceptible to the activity of the extract (MIC 0.08 mg mL-¹, MBC 0.16 mg mL-¹). Furthermore, methanolic extract of P. involutus demonstrated genotoxicity, severe hemolysis effects and selective cytotoxicity against colon cancer cells. From the obtained data, it may be concluded that investigated mushroom albeit being toxic for human consumption, may be considered as a source of highly bioactive components with potential application in drug development.

The multistrain probiotics' efficacy in ameliorating the endotoxemic effect in Lipopolysaccharide (LPS) challenged mice was evaluated with the agonist of anti-inflammatory peptide, neurotensin (NTS), especially targeting the inflammation of the gut and liver. Swiss Albino Mice (Female, 8 weeks old) were maintained in eight groups: Group I as Control, Group II-Group V were exposed to intraperitoneal (i.p.) LPS (1 mg/kg bw) for 5 days. After that, Group III and Group VI were administered probiotics orally (0.6 gm/kg bw/day), Group IV and Group VII with NTS receptor 1 (NTSR1) agonist PD149163 (50 µg/kg bw/day i.p.), and Group V and Group VIII co-administered with probiotics and PD149163 for 28 days. Group II (LPS-exposed) was maintained without any further treatment; mice of all the groups were sacrificed at day 34. In the LPS-exposed mice, endotoxemia was distinct from a significant (P < 0.001) increase of plasma pro-inflammatory cytokines (TNF-α; IL-6), a decrease of anti-inflammatory cytokine (IL-10), oxidative stress, and inflammation of the gut and liver. Increased serum transaminases indicated hepatic inflammation. A decreased population of the bifidobacteria and increased clostridia indicated microbiota dysbiosis. Probiotics when used as an adjunct along with PD149163 have shown better efficacy in inflammation modulation as reflected in the significantly decreased (P < 0.001) inflammatory mediators, oxidative stress, restoration of the beneficial bacterial population, along with a significant reduction in histopathological scores of the gut and the liver than when used alone. This study suggests probiotics could be used as an adjunct in clinical practice along with anti-inflammatory drugs for better therapeutic efficacy.

This study is aimed to evaluate the impact of methanolic extract of Artemisia vulgaris and isolated plant compound, β-Caryophyllene oxide against carrageenan-induced paw edema in rat model and its therapeutic potential compared with reference drug, Indometacin. Methanolic extract of A. vulgaris was characterized using FTIR, LC-MS, NMR spectral studies. Paw edema was induced by sub-plantar injection of 100 µl of 1% carrageenan. Oxidative enzymes, such as super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), lipid peroxidation and C-reactive protein levels were measured in paw tissue. In silico evaluation of anti-inflammatory activity of plant compounds was evaluated against the molecular targets of inflammation. C-reactive protein and lipid-peroxidation levels were significantly increased whereas the activity levels of oxidative enzymes were significantly decreased in inflammation-induced rats. The recovery of oxidative enzyme levels was seen in treated groups in a dose dependent manner. C-reactive protein and lipid-peroxidation levels were significantly decreased in treated groups, indicating the anti-inflammatory activity of the plant extract and the plant compound. Computational analysis rationalizes the inhibitory ability of plant derived compound possibly by altering the inflammatory signaling pathway.

Alpha-terpineol (α-T) is a type of monoterpenoid alcohol commonly present in essential oils, it contributes to a pleasant floral fragrance similar to that of lilacs. This research aimed to evaluate the impact of α-terpineol on the reproductive functions of both male and female rats, including gonadal activity, mating behavior, conception, conceptus development and parturition. Six male and female Wistar rats per group received α-terpineol through gavage at doses of 0, 75, 150 and 300 mg/kg/day. The study revealed changes in body weight gain inhibition, food consumption, azoospermia, decreased testosterone levels (0.7 ± 1.61 ng/mL, 0.7 ± 2.30 ng/mL) as well as histopathological variations in testis and epididymis among males exposed to doses of 150 and 300 mg/kg/day. Moreover, this exposure led to significantly decreased serum T4 levels in both adult males (21.85 ± 12.68 ng/mL, 16.20 ± 9.15 ng/mL) and dams (11.24 ± 12.37 ng/mL, 9.48 ± 11.74 ng/mL) at the dose range of 150 and 300 mg/kg/day without affecting TSH concentrations. In summary, the present study showed that α-terpineol induced reproductive toxicities in male rats. Therefore, a detailed toxicological assessment is highly recommended.

Aquatic communities are increasingly exposed to complex mixtures of contaminants, mainly pesticides due to the impact of agricultural activity. The aim of this study was to evaluate the toxicity of an eight-pesticide cocktail on larvae of the South American common toad, Rinella arenarum. The cocktail represents a realistic mixture of insecticides (cypermethrin, chlorpyrifos and lambda-cyhalothrin), herbicides (glyphosate, glufosinate ammonium, prometryn and metolachlor), and a fungicide (pyraclostrobin) previously found in aquatic organisms (Prochilodus lineatus) from the Salado River Basin, an area with strong agricultural pressure. Computational simulations through the Density Functional Tight-Binding method indicated a strong spontaneous trend toward the formation of the cocktail, suggesting that it may act as a novel xenobiotic entity in the environment. The cocktail effects were evaluated in early-developing and premetamorphic larvae, at feasible concentrations found in real scenarios. The mixture led to high mortality and teratogenicity in early-developing larvae. Premetamorphic larvae showed endocrine disruption, oxidative stress, and impairments in detoxification and hepatic functioning. Neurotoxicity, genotoxicity, cardiotoxicity and high mortality under stress conditions were also observed in exposed larvae. This novel evaluation highlights the ecotoxicological risk for aquatic organisms exposed to complex mixtures and underscores the need to consider cocktail effects in studies regarding ecosystems health.

The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47-103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

Objectives: Metabolic disorders, as multifactorial disorders, are induced by genetic susceptibility and exposure to environmental chemicals. Di (2-ethyl hexyl) phthalate (DEHP), a ubiquitous plasticizer, is well known as an endocrine-disrupting chemical in living organisms. In recent decades, researchers have focused on the potential of DEHP and its main metabolite (Mono (2-ethylhexyl) phthalate) (MEHP) to induce metabolic disorders. In the present review, we aimed to summarize studies regarding DEHP and MEHP-induced Metabolic syndrome (MetS) as well as address the involved mechanisms.

Methods: A search has been carried out in Google Scholar, PubMed, Scopus, and Web of Science databases using appropriate keywords including 'Metabolic syndrome' or 'Metabolic disorder' or 'Obesity' or 'Hyperglycemia' or 'Hyperlipidemia' or 'Hypertension' or 'Non-alcoholic fatty liver disease' and 'DEHP' or 'Di (2-ethyl hexyl) phthalate' or 'Bis(2-ethylhexyl) phthalate' or 'MEHP' or 'Mono (2-ethylhexyl) phthalate'. Studies were chosen based on inclusion and exclusion criteria. Inclusion criteria are in vitro, in vivo, epidemiological studies, and English-written studies. Exclusion criteria are lack of access to the full text of studies, editorial articles, review articles, and conference articles.

Results: Animal studies indicate that DEHP and MEHP disrupt insulin hemostasis, increase glucose content, and induce hyperlipidemia and hypertension as well as obesity, which could lead to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). DEHP and its metabolite induce such effects directly through influence on nuclear receptors such as peroxisome proliferator-activated receptors (PPARs) or indirectly through reactive oxygen species (ROS) production. Both events led to the disruption of several molecular signaling pathways and subsequently metabolic syndrome (MetS). Furthermore, epidemiological studies showed that there was a correlation between DEHP metabolites levels and obesity, hyperglycemia, and hypertension.

Conclusions: According to studies, DEHP and its main metabolite have the potential to induce MetS by involving various molecular mechanisms. Epidemiological studies concerning the association of DEHP and MetS in humans are not sufficient. Therefore, more studies are needed in this regard.

The cultivation of tilapias, the third most farmed fish group globally, has been rapidly growing, especially in Southeast Asia. This surge in tilapia farming intensification has led to increased use of antibiotics to control bacterial diseases. This study investigated the safety implications of administering graded doses of enrofloxacin (ENF) at 0 (control), 10, 30, 50 and 100 mg/kg biomass/day orally to Oreochromis niloticus. The 43-day study comprised 7 days of pre-dosing, 15 days of ENF-dosing, and a 21-day recovery period with a periodical assessment of the biological responses of fish. The results revealed that the overdosed groups experienced up to 21% reduction in feed consumption, 11% mortalities, and adverse impacts on hematology, including a decrease in erythrocytes, and monocytes and an increase in leukocytes, thrombocytes, lymphocytes, and neutrophils. Haematological indices like mean corpuscular volume and mean corpuscular hemoglobin decreased, while mean corpuscular hemoglobin concentration increased. The plasma biochemical parameters including glucose and liver and kidney enzymes unveiled a significant dose- and time-dependent increase, while calcium and chloride levels decreased. Erythrocytes displayed several erythrocyte cellular and nuclear abnormalities. The frequency of micronucleus increased with dose and time, suggesting potential genotoxicity of ENF. Additionally, a dose-dependent increase in residues in the tissues with the highest accumulation in muscle was documented. Nevertheless, the recovery of the measured parameters upon dose termination indicated that the ENF-induced alterations are reversible. The study affirmed the safety of ENF at the recommended dose (10 mg) in O. niloticus and their adoptive responses to higher doses.

In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.