Drug and Chemical Toxicology最新文献

Due to its antioxidant action, the carotenoid lycopene has been demonstrated to have a protective effect in several disease models; however, its effect on the nanoform of titanium oxide (nano-TiO₂)-induced neurotoxicity has not yet been determined. The purpose of this study was to evaluate how lycopene affects neuronal damage brought on by nano-TiO₂ and the mechanisms involved. SH-SY5Y cells were treated with different concentrations of nano-TiO₂ for 48 hours, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used after that to evaluate cell viability. IC₅₀ of nano-TiO₂ was determined and the results revealed that IC₅₀ is equal 40 µM/mL, lycopene (10 µM) was applied to SH-SY5Y human neuroblastoma cells an hour before exposure to 40 µM nano-TiO₂. Reactive oxygen species, lipid peroxidation, nitric oxide, glutathione, superoxide dismutase, and catalase, tumor necrosis factor-alpha, interleukin 1 beta, nuclear factor kappa B, and apoptotic markers (Bcl2, Bax, and caspase-3), were measured to determine the anti-oxidant effect of lycopene. In SH-SY5Y neuroblastoma cells, pretreatment with 10 µM lycopene significantly reduced the toxicity brought on by exposure to nano-TiO₂, according to MTT assay findings and lactate dehydrogenase (LDH) cytotoxicity assessment. In cells exposed to nano-TiO₂, lycopene pretreatment significantly boosted the activity of antioxidative enzymes and reduced oxidative stress. Furthermore, when SH-SY5Y cells were subjected to nano-TiO₂, lycopene pretreatment stopped neuroinflammation and apoptosis. The findings of this study suggest that lycopene may be an effective neuroprotective against oxidative stress and neuroinflammation and may be used to stop neuronal death or injury in a variety of neurological illnesses.

Sulfur mustard (SM) exposure has delayed harmful effects, including premature biological aging. This study aimed to evaluate the expression of aging markers (i.e., ANRIL, P16^INK4a, TBX2, and TERRA) and assess their correlation with the severity of SM exposure in the long term. The study was conducted on two volunteer groups. 1) SM-exposed group, exposed to SM once in 1987 during the war; divided into three subgroups based on the injury severity, asymptomatic (without any clinical signs), mild, and severe; 2) Non-exposed group. In the SM-exposed group, ANRIL transcript was decreased, especially in subgroups of mild and severe. TBX2 transcript was also decreased in the total SM-exposed group. This decrease was more significant in the mild and severe subgroups than in asymptomatic ones. P16^INK4a transcript was increased in the SM-exposed group, especially in the asymptomatic subgroup. The increase in TERRA transcript was also significant in all subgroups. There was a positive correlation between the TERRA transcript and the severity of injury, while this correlation was negative for the ANRIL. It is concluded that the delayed toxicity of SM may be associated with dysregulation of aging markers leading to premature cellular aging. These markers' alterations differed according to the severity of SM injury.

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175-5,000 mg·kg^-1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg^-1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.

Despite the cytotoxicity and embryotoxicity previously reported artesunate is a recommended drug to treat malaria for adults, children, and women in the first trimester of pregnancy. To address the putative effects of artesunate on female fertility and preimplantation embryo development, when the pregnancy is not detectable yet, artesunate was added to the oocyte in vitro maturation and in vitro embryo development of bovine. Briefly, in experiment 1 the cumulus-oocyte complexes (COCs) were in vitro matured for 18 h with 0.5, 1, or 2 µg/mL of artesunate or not (negative control) and then checked for nuclear maturation and subsequent embryo development. In experiment 2, the COCs were in vitro matured and fertilized without artesunate, which was added (0.5, 1, or 2 µg/mL) from the 1st to the 7th day of embryo culture along with a negative and a positive control group with doxorubicin. As a result, the use of artesunate on oocyte in vitro maturation did not differ from the negative control (p > 0.05) regarding nuclear maturation, cleavage, and blastocyst formation. Also, artesunate on in vitro embryo culture did not differ from negative control (p > 0.05) regarding cleavage and blastocyst formation, except for positive control, with doxorubicin (p < 0.05). In conclusion, under the conditions investigated, there was no evidence of artesunate toxicity on oocyte competence and the preimplantation period of in vitro embryo development in the bovine model, however, artesunate use still should be taken carefully as the outcome of implantation after oocytes and blastocysts exposure to artesunate remains unknown.

Chlorpyrifos (CPF) is a widely used pesticide that can impair body organs. Nonetheless, metformin is known for its protective role against dysfunction at cellular and molecular levels led by inflammatory and oxidative stress. This study aimed to investigate the modulatory impacts of metformin on CPF-induced heart and lung damage. Following the treatment of Wistar rats with different combinations of metformin and CPF, plasma, as well as heart and lung tissues, were isolated to examine the level of oxidative stress biomarkers like reactive oxygen species (ROS) and malondialdehyde (MDA), inflammatory cytokines such as tumor necrosis alpha (TNF-α), high mobility group box 1 (HMGB1) gene, deoxyribonucleic acid (DNA) damage, lactate, ADP/ATP ratio, expression of relevant genes (TRADD, TERT, KL), and along with histological analysis. Based on the findings, metformin significantly modulates the impairments in heart and lung tissues induced by CPF.

This study investigated the capability of a co-delivery system of thymol (THY) and sulfoxaflor that can serve to minimize the development of epididymal and testicular injury arise from SFX exposures alone. Forty-eight adult male rats were orally treated by gavage for 28 consecutive days. The rats were divided into six groups comprising control, THY alone (30 mg/kg), low SFX alone (79.4 mg/kg), high SFX alone (205 mg/kg) and co-exposure groups. After euthanasia, the rats epididymal and testicular damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 b (IL-1β) and caspase-3 activity were assessed using ELISA kits. The results revealed that SFX exposure caused a significant (p < 0.05) decrease in the body weight, sperm functional parameters, serum testosterone level with widespread histological abnormalities in a dose-dependent manner. Increased relative organ weights, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were observed in low SFX-treated rats. Similarly, the epididymal and testicular myeloperoxidase activity, malondialdehyde (MDA), reactive oxygen species (RONS), tumor necrosis-α, interleukin-1β levels and caspase-3 activity were significant (p < 0.05) increased and a significant (p < 0.05) reduction in antioxidant enzyme activities and reduced glutathione (GSH) were revealed in SFX-treated rats. However, co-treatment of THY with SFX prevented SFX-induced epididymal and testicular toxicities. Thus, thymol protected against potential epididymis and testes alterations elicited by oxido-inflammatory mediators and up regulated antioxidant status.