Perfluorooctane sulfonate (PFOS) is reported to cause hepatotoxicity in animals and humans. However, the underlying mechanism by which it affects organelle toxicity in the liver are not well elucidated yet. This study aimed to investigate the mechanisms underlying PFOS-induced hepatic toxicity, focusing on inflammation, cell death, and autophagy. We established a PFOS-exposed Sprague-Dawley (SD) rat liver injury model by intraperitoneal injection of PFOS (1 mg/kg and 10 mg/kg body weight) every alternate day for 15 days. Our findings indicated that PFOS increased liver weight, caused lipid disorder and hepatic steatosis in rats. Meanwhile, PFOS disrupted the structure of mitochondria, increased accumulation of reactive oxygen species (ROS), repressed superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels, and elevated malondialdehyde (MDA) and nitric oxide synthase (NOS) amounts. We found PFOS induced inflammation as evidenced by activation of NOD-like receptor protein 3 (NLRP3), Cleaved cysteine-aspartic acid protease (caspase)1, tumor necrosis factor (TNF)α and interleukin (IL)-1β levels. Moreover, PFOS exposure significantly decreased B-cell lymphoma2 (Bcl2)/Bcl2 associated X (Bax) ratio and increased the protein expression of Cleaved caspase-3. Compared with the control group, PFOS upregulated the protein expression of necroptotic markers and autophagy-related proteins. In conclusion, PFOS induced inflammation, cell death, and autophagy through oxidative stress by ROS overload, thereby providing a mechanistic explanation for PFOS-induced hepatotoxicity.

A physiologically based kinetic (PBK) model is used for predicting chemical concentrations of toxicological concern in target tissues. Such models are important for understanding toxicokinetics. However, it is challenging to obtain chemical-specific empirical parameter values used for PBK modeling. Thus, developing methods predicting these values is necessary. Herein, we researched PBK models of inhalation exposure to industrial chemicals and developed a database of parameters of approximately 200 chemicals in humans and rodents. Next, the chemicals in the database were classified into three categories (I, IIA, and IIB) based on the intermolecular interactions for humans and rats. Quantitative relationships between blood/air and tissue/blood partition coefficients and physicochemical parameters were derived for the chemicals in each category. Regression analyses of blood/air and fat/blood partition coefficients against Henry’s law constant and log D at pH 7.4 for chemicals in category IIA for humans, in which van der Waals and dipole–dipole interactions were involved, yielded 0.88 and 0.54 coefficients of determination, respectively. Moreover, these methods worked for other categories and species. The metabolic parameters maximal velocity (Vmax) and Michaelis–Menten constant (Km) of the chemicals that are primarily metabolized by cytochrome P450 were calculated for humans and rats. Multiple regression analyses of logs Vmax and Km against the occurrence frequency of molecular fragments showed good correlations, respectively. The aforementioned models predicted values close to the reported values for test chemicals within the applicability domains. Our approach could also be applied to other chemicals within the domains that are not included in the database.

Acute carbon monoxide poisoning (ACOP) is a cause of accidental or deliberate deaths worldwide. Subsequent complications, particularly delayed neurological sequelae (DNS), are preventable and treatable based on their pathophysiology. Hyperbaric oxygenation therapy (HBO) is a potential procedure for preventing and treating DNS; however, the effects of HBO on DNS are unclear and debated. In the present study, we investigated which factors are associated with the development of DNS and the effects of HBO in patients with ACOP. We performed retrospective subanalyses of the COP-J registry, focusing on adults who underwent HBO, regardless of whether they developed DNS. The multivariable analysis showed that the Glasgow coma scale (GCS) on admission was significantly associated with DNS (odds ratio 0.736; 95% confidence interval 0.608–0.892; P = 0.002). The receiver operating characteristic curve analysis of GCS for DNS revealed a cutoff value of 12.5 according to Youden’s index (sensitivity 80.8%, specificity 76.9%). This retrospective analysis of a nationwide Japanese registry of ACOP showed that low GCS scores on admission could be a predictive factor for DNS, with a possible cutoff value of ≤12, in patients who undergo HBO.

The surface of a rotting corpse is covered with liquid decomposition products that have flowed out of the body that include putrefactive amines produced via putrefaction and decarboxylation reactions of proteins. Ammonia generated by deamination is also present around the corpse as a liquid or gas. As these putrefactive substances are toxic to humans, we attempted to measure the concentration of putrefactive substances in decomposed corpses in this study. Liquid putrefaction products were collected from the surface of a corpse, and the concentrations of putrefactive amines such as histamine, tyramine, phenethylamine, and tryptamine were analyzed by LC-MS/MS. Ammonia in the liquid and air around the corpse was also measured. Putrefactive amines and ammonia were present on all corpse surfaces. The highest concentrations and postmortem days in parentheses were as follows: histamine 2.26 mg/g (15 days), tyramine 1.77 mg/g (16 days), phenethylamine 4.90 mg/g (24 days), tryptamine 1.58 mg/g (17 days) and ammonia 25.6 mg/g (24 days postmortem). The highest concentration of ammonia in the air was 1310 ppm at 24 days postmortem. The ammonia level in the air around a corpse is toxic to humans. Inhalation of putrefactive amines and ammonia can cause chemical irritation to the respiratory tract and the skin and damage the mucous membrane of the eye. Oral ingestion can also cause poisoning symptoms such as blood pressure changes and headaches. Adequate protection against putrefactive substances is required when in contact with decaying corpses.

Attainment of vaginal patency is an endpoint for the onset of puberty in female animals in toxicity studies. It is widely acknowledged that certain substances with endocrine-modulating effects can influence the timing of puberty in female rats and that factors unrelated to endocrine mechanisms, such as malnutrition and stress, can also affect pubertal onset. Some epidemiological studies have also suggested a link between anemia and delay in pubertal onset in women, however, little is known regarding the relation between hematological changes and female pubertal onset in experimental animals. The purpose of this study was to examine the effects of anemia during the prepubertal period on pubertal onset and reproductive organs in female rats. In this study, anemia was induced by drawing a certain amount of blood from the jugular vein or by intraperitoneal administration of phenylhydrazine, a well-known inducer of hemolytic anemia. As a result, both treatment groups showed a transient anemia characterized by an approximately 20-35% decrease in hemoglobin levels compared to the control group. Anemia in these female rats produced no obvious changes in body weight on each postnatal day and had no effect on the weights and histopathology of reproductive organs after sexual differentiation, but the age at vaginal opening (VO) was delayed and the body weight at VO was higher than the same parameters in the control group. These results suggest that anemia in prepubertal females could cause a delay in pubertal onset.