The alleviation effect and its mechanism of Niuhuang Jiedu prescription on realgar-induced genotoxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar (As2S2 or As4S4) is a traditional Chinese medicine (TCM) containing arsenic. Existing studies have shown that it has genotoxicity under long-term use with large doses. Niuhuang Jiedu (NHJD) is a Chinese medicine prescription containing realgar and seven other TCMs. Whether the multiple TCMs combination in NHJD can reduce the genotoxicity induced by realgar in equivalent doses is still unknown. AIM OF THE STUDY: To research the effect of NHJD on realgar's genotoxicity and the possible mechanism involved based on the arsenic methylation metabolic pathway. MATERIAL AND METHODS: Six groups (control, realgar (0.8 g/kg), NHJD (12.48 g/kg), as well as Glycyrrhiza uralensis Fisch (GU), Scutellaria baicalensis Georg (SB), Rheum palmatum L (RP) plus equivalent doses of realgar, respectively) were set up. ICR mice were intragastric administered for 12 weeks. First, genotoxicology tests were conducted to evaluate the effect of NHJD, GU, SB, and RP on reducing realgar's genotoxicity. The inorganic arsenic (iAs), dimethyl arsenic acid (DMA), and monomethyl arsenic acid (MMA) were determined by HPLC-AFS, and the iAs%, MMA%, DMA%, primary methylation index (PMI), etc. Were calculated. Meanwhile, the S-adenosyl methionine (SAM) and arsenate reductase (ARR) levels, the arsenic (+3)methyltransferase (As3MT), purine-nucleoside phosphorylase (PNP), glutathione S-transfer omega1 (GSTO1) gene expression were detected, aimed to explore the possible alleviation mechanisms of NHJD. RESULTS: The combination of multiple TCMs in NHJD decreased the levels of MN‰, SPA%, and DNA damage caused by realgar, with similar effects observed when SB, RP, and GU were used separately with realgar. Notably, the iAs% significantly decreased, while DMA% and PMI notably increased in the NHJD and realgar + SB (or RP) groups compared to the realgar-only group (P < 0.05). Increases in SAM and ARR levels were observed across various groups, but only the ARR increase in the NHJD group was statistically significant. Moreover, significant increases in As3MT mRNA and GSTO1 mRNA were noted in the NHJD group, and PNP mRNA levels significantly rose in the realgar + SB group. CONCLUSIONS: This study revealed that NHJD could attenuate the genotoxic effects of realgar. The botanicals SB, RP, and GU within NHJD may be key contributors to this effect. Enhancements in arsenic methylation capabilities through increased levels of SAM and ARR and elevated gene expressions of As3MT, PNP, and GSTO1 suggest potential mechanisms behind these findings.

Intrauterine arsenic exposure induces glucose metabolism disorders in adult offspring by targeting TET2-mediated DNA hydroxymethylation reprogramming of HNF4α in developing livers, an effect alleviated by ascorbic acid.

Exposure to arsenic during gestation has lasting health-related effects on the developing fetus, including an increase in the risk of metabolic disease later in life. Epigenetics is a potential mechanism involved in this process. Ten-eleven translocation 2 (TET2) has been widely considered as a transferase of 5-hydroxymethylcytosine (5hmC). Here, mice were exposed, via drinking water, to arsenic or arsenic combined with ascorbic acid (AA) during gestation. For adult offspring, intrauterine arsenic exposure exhibited disorders of glucose metabolism, which are associated with DNA hydroxymethylation reprogramming of hepatic nuclear factor 4 alpha (HNF4α). Further molecular structure analysis, by SEC-UV-DAD, SEC-ICP-MS, verified that arsenic binds to the cysteine domain of TET2. Mechanistically, arsenic reduces the stability of TET2 by binding to it, resulting in the decrease of 5hmC levels in Hnf4α and subsequently inhibiting its expression. This leads to the disorders of expression of its downstream key glucose metabolism genes. Supplementation with AA blocked the reduction of TET2 and normalized the 5hmC levels of Hnf4α, thus alleviating the glucose metabolism disorders. Our study provides targets and methods for the prevention of offspring glucose metabolism abnormalities caused by intrauterine arsenic exposure.

Gas sensor based on samarium oxide loaded mulberry-shaped tin oxide for highly selective and sub ppm-level acetone detection.

Mulberry-shaped tin oxide (SnO2) hierarchical architectures and samarium oxide (Sm2O3) loaded tin oxide with different amounts (0.5, 1, 2.5, and 4 mol% Sm2O3) were successfully synthesized by facile hydrothermal synthesis method and simple isometric impregnation method. The gas sensing performance of the sensors based on pure SnO2 and Sm2O3 loaded SnO2 materials were systematically investigated. The results indicated that Sm2O3 loading considerably affected the improvement of the sensing performance of the SnO2 sensor. The 2.5 mol% Sm2O3/SnO2 exhibited the highest response (41.14) to 100 ppm acetone, the response was 2.29 times higher than that of pure SnO2 (18). In addition, with 2.5 mol% Sm2O3 loading, the low detection threshold of the sensor dropped from 500 ppb to 100 ppb. The enhanced gas sensing performance was mainly bacause of the increased oxygen vacancies created by the substitution of samarium in the SnO2 lattice, which enhanced the adsorption of oxygen and the exceptional catalytic effect of Sm2O3.

[Distribution of rubidium, cesium, beryllium, strontium, and barium in blood and urine in general Chinese population].

OBJECTIVE: To investigate the distribution of rubidium (Rb), cesium (Cs), beryllium (Be), strontium (Sr), and barium (Ba) in blood and urine in general Chinese population. METHODS: A total of 18 120 subjects aged 6~60 years were enrolled from 24 regions in 8 provinces in Eastern, Central, and Western China from 2009 to 2010 based on the method of cluster random sampling. Questionnaire survey was conducted to collect the data on living environment and health status. Blood and urine samples were collected from these subjects, and the levels of Rb, Cs, Be, Sr, and Ba in these samples were determined by inductively coupled plasma mass spectrometry. The distribution of these elements in blood and urine in male or female subjects living in different regions was analyzed statistically. RESULTS: In the general Chinese population, the concentration of Be in the whole blood was below the detection limit (0.06 µg/L); the geometric mean (GM) of Ba in the whole blood was below the detection limit (0.45 µg/L), with the 95th percentile (P95)of 1.37 µg/L; the GMs (95% CI)of Rb, Cs, and Sr in the whole blood were 2 374(2 357~2 392) µg/L, 2.01 (1.98~2.05) µg/L, and 23.5 (23.3~23.7) µg/L, respectively; in males and females, the GMs (95%CI)of blood Rb, Cs, and Sr were 2 506 (2 478~2 533) µg/L and 2 248 (2 227~2 270) µg/L, 1.88 (1.83~1.94) µg/L and 2.16 (2.11~2.20) µg/L, and 23.4 (23.1~23.7) µg/L and 23.6 (23.3~23.9) µg/L, respectively(P<0.01, P>0.05, and P>0.05). In the general Chinese population, the GM of urine Be was below the detection limit (0.06 µg/L), while the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 854 (836~873) µg/L, 3.65 (3.56~3.74) µg/L, 39.5 (38.4~40.6) µg/L, and 1.10 (1.07~1.12) µg/L, respectively; in males and females, the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 876 (849~904) µg/L and 832 (807~858) µg/L, 3.83 (3.70~3.96) µg/L and 3.47 (3.35~3.60) µg/L, 42.5 (40.9~44.2) µg/L and 36.6 (35.1~38.0) µg/L, and 1.15 (1.12~1.19) µg/L and 1.04 (1.01~1.07) µg/L, respectively (all P< 0.01). Correlation analyses showed that there were weak correlations between blood Rb and urine Rb (r=0.197)and between blood Sr and urine Sr (r=0.180), but a good correlation between blood Cs and urine Cs (r=0.487). CONCLUSION: The levels of Rb, Cs, Be, Sr, and Ba in the general Chinese population are similar to those reported in other countries, and there is a significant difference in the concentration of each element among the populations living in different regions, as well as significant differences in blood Rb, urine Rb, urine Cs, urine Sr, and urine Ba between males and females.

[Study of distribution and influencing factors of lead and cadmium in whole blood and urine among population in 8 provinces in China].

OBJECTIVE: To evaluate the levels of lead (Pb) and cadmium (Cd) in blood and urine among general population in China, and thereby analyze their prevalent features. METHODS: A total of 18 120 subjects from general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland from 2009 to 2010, by cluster random sampling method. The blood samples and urine samples of these people were collected. The questionnaire survey was used to collect the information of the living environment and health conditions.Inductive coupled plasma mass spectrometry was applied to test the Pb and Cd levels in the samples, and the distribution of Pb and Cd in blood and urine for different ages, genders, areas and life habits were then analyzed. RESULTS: Among the general population in China, the geometric mean (GM) of blood Pb concentration was 34.9 µg/L; the GM of blood Pb in male and female groups were 40.1 and 30.4 µg/L (Z = -28.05, P < 0.05), respectively; the GM from eastern, central and western China were 31.2, 38.8 and 58.9 µg/L (χ(2) = 1 483.33, P < 0.05) , respectively. The GM of urine Pb of the whole population was 1.05 µg/L;while the GM in male and female groups were 1.06 µg/L and 1.05 µg/L (Z = -0.73, P > 0.05) , respectively;the values from eastern, central and western China were 0.76, 2.85 and 3.22 µg/L (χ(2) = 1 982.11, P < 0.05), respectively. The GM of blood Cd concentration among general population was 0.49 µg/L; and the values in male and female group were 0.60 and 0.41 µg/L (Z = -11.79, P < 0.05) , respectively; the GM from eastern, central and western China were 0.45, 0.65 and 0.67 µg/L (χ(2) = 69.87, P < 0.05), respectively; the GM of urine Cd concentration of the whole population was 0.28 µg/L, while the GM in male and female groups were 0.29 and 0.28 µg/L (Z = -3.86, P < 0.05), respectively; the values from eastern, central and western China were 0.29,0.42 and 0.18 µg/L (χ(2) = 402.76, P < 0.05), respectively. the Spearman's rank correlation coefficient for Cd in blood and Cd in urine was 0.22, for Pb in blood and Pb in urine was 0.21. Both the correlations were statistic significant (P < 0.05). CONCLUSION: The Pb and Cd levels in blood and urine were relatively higher among general population in China varying by gender and area. There were positive correlations between Pb and Cd levels in blood and those in urine.