Conventional and multi-omics assessments of subacute inhalation toxicity due to propylene glycol and vegetable glycerin aerosol produced by electronic cigarettes.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Influences of Unmodified and Carboxylated Carbon Nanotubes on Lipid Profiles in THP-1 Macrophages: A Lipidomics Study.

Since the possible roles of surface modifications in determining multi-walled carbon nanotube (MWCNT)-promoted endoplasmic reticulum (ER) stress-mediated lipid-laden macrophage foam cell formation are still in debate, we compared unmodified and carboxylated MWCNT-induced cytotoxicity, lipid profile changes, and expression of ER stress genes in THP-1 macrophages. Particularly, we focused on lipid profile changes by using lipidomics approaches. We found that unmodified and carboxylated MWCNTs significantly decreased cellular viability and appeared to damage the cellular membrane to a similar extent. Likewise, the results from Oil Red O staining showed that both types of MWCNTs slightly but significantly induced lipid accumulation. In keeping with Oil Red O staining results, lipidomics data showed that both types of MWCNTs up-regulated most of the lipid classes. Interestingly, almost all lipid classes were relatively higher in carboxylated MWCNT-exposed THP-1 macrophages compared with unmodified MWCNT-exposed cells, indicating that carboxylated MWCNTs more effectively changed lipid profiles. But in contrast to our expectation, none of the MWCNTs significantly induced the expression of ER stress genes. Even, compared with carboxylated MWCNTs, unmodified MWCNTs induced higher expression of lipid genes, including macrophage scavenger receptor 1 and fatty acid synthase. Combined, our results suggested that even though carboxylation did not significantly affect MWCNT-induced lipid accumulation, carboxylated MWCNTs were more potent to alter lipid profiles in THP-1 macrophages, indicating the need to use omics techniques to understand the exact nanotoxicological effects of MWCNTs. However, the differential effects of unmodified and carboxylated MWCNTs on lipid profiles might not be related with the induction of ER stress.

Acute and Subchronic Oral Toxicity of Anthraquinone in Sprague Dawley Rats.

Objective: This study was conducted to evaluate the acute and subchronic toxicity of anthraquinone. An acute toxicity test was performed in female Sprague Dawley (SD) rats, and the oral median lethal dose (LD50) of anthraquinone was estimated to be >5000 mg/kg body weight (BW). In the subchronic study, groups of 10 male and 10 female rats were dosed with anthraquinone by gavage at 0, 1.36, 5.44, 21.76, and 174.08 mg/kg BW, 7 days/week for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 1.36 mg/kg BW group. When the animals received 5.44 mg/kg BW or more of anthraquinone, hyaline droplet accumulation in the renal tubules was observed in both the male and female rats, and anemia was observed in the females. When the anthraquinone dose reached 174.08 mg/kg BW, mild hepatocellular hypertrophy around the central vein of the hepatic lobule and hypothyroidism were observed in the female rats. During the recovery period, changes in clinical symptoms and parameters were considerably alleviated. Based on the results of this study, the no observed adverse effect level (NOAEL) for anthraquinone in rats was set at 1.36 mg/kg BW, and the lowest observed adverse effect level (LOAEL) was 5.44 mg/kg BW.

Subchronic Toxicity of GmDREB3 Gene Modified Wheat in the Third Generation Wistar Rats.

The aim of the current study was to evaluate the subchronic toxicity of GmDREB3 gene modified wheat in the third generation rats. SPF Wistar rats were fed with transgenic wheat diet (Gm), parental wheat diet (Jimai22) and AIN-93 rodent diet (Control), respectively, for two generations, to produce the third generation rats which were used for this study. The selected fresh weaned offspring rats (20/sex/group) were given the same diet as their parents for 13 weeks. No toxicity-related changes were observed in rats fed with Gm diet in the following respects: clinical signs, body weights, body weight gains, food consumption, food utilization rate, urinalysis, hematology, serum biochemistry and histopathology. The results from the present study demonstrated that 13 weeks consumption of Gm wheat did not cause any adverse effects in the third generation rats when compared with the corresponding Jimai22 wheat.

Chronic toxicity study in Sprague-Dawley rats on transgenic rice T1c-19 with cry1C* gene.

In the present study, a novel transgenic rice line T1c-19 carrying cry1C* gene was evaluated in Sprague-Dawley (SD) rats by a 52-week feeding study, aiming at determining its unintended effects. The rice T1c-19 and its parental rice were prepared at a level of up to 60.75% in the growth diet and 66.75% in the maintenance diet, respectively. AIN-93 diet was used as a nutritional control. All the diets were nutritionally balanced. Each group, with 48 rats of both genders, was fed the corresponding diet for 52 weeks. The results of clinical signs, body weight and food consumption of the transgenic rice group were comparable to those of the parental rice group. Clinical measurements were made on weeks 13, 26 and 52, and statistical significances were observed in several hematological and serum biochemical indices between the two rice groups and were not considered as treatment-related. The terminal histopathological examination showed some spontaneous lesions in all groups with no significant difference among them. Taken together, the results of the present 52-week chronic toxicity study of transgenic rice T1c-19 exerted no unintended adverse effects on SD rats.

[Effect of San-huang-sheng-fu oil on wounds of full-thickness scald in rabbits].

OBJECTIVE: To observe the effect of San-huang-sheng-fu oil on wounds of full-thickness scald in rabbits. METHODS: Full-thickness scald wounds with area of 6 cm(2) were reproduced on both sides of the back in 9 experimental rabbits by water vapor. These rabbits were divided into sesame oil (S1), San-huang-sheng-fu oil (S2), and mupirocin ointment (M) groups according to the random number table, with 3 rabbits (6 wounds) in each group. Two wounds of each rabbit in the three groups were respectively treated with sesame oil, San-huang-sheng-fu oil, and mupirocin ointment, in a dose of 0.15 mL/cm(2), 2-3 times per day. The general condition of wounds was observed on post scald day (PSD) 1, 11, 22, and 45. The wound healing time was recorded. The wound healing rate was calculated on PSD 5, 11, 15, and 22. All the rabbits were sacrificed on PSD 45, and wound tissues were subjected to histomorphological study with HE staining. The protein expressions of transforming growth factor ß1 (TGF-ß1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were observed with immunofluorescence staining for the other part of wound tissues. Data were processed with one-way analysis of variance or LSD-t test. RESULTS: (1) The wound healing quality of rabbits in S2 group was better than that in the other two groups. (2) The wound healing time of rabbits in S2 group [(11.2 ± 2.3) d] was significantly shorter than that in S1 group [(21.2 ± 3.1) d, t = 2.591, P < 0.05]. (3) The wound healing rate of rabbit in each group was increased gradually on PSD 5-22. The wound healing rates of rabbits in S2 group on PSD 5-22 were significantly higher than those in S1 group (with t values from 3.920 to 8.605, P values all below 0.05). (4) Histomorphological observation showed that the structure of wound tissues in S2 group was in much better integrity than that in the other two groups, including regenerated hair follicles in the corium layer and regularly arranged collagen fibers. The protein expressions of TGF-ß1, bFGF, and VEGF in S2 group were all higher than those in the other two groups. CONCLUSIONS: San-huang-sheng-fu oil can up-regulate the protein expressions of TGF-ß1, bFGF, and VEGF, induce vascular regeneration, promote wound healing, and shorten wound healing time.