ABSTRACT
Objective@#To examine the effects of bisphenol A (BPA), bisphenol S ( BPS ), bisphenol F ( BPF ) and bisphenol AF ( BPAF ) on the proliferation and oxidative stress of BRL 3A rat liver cells, and to preliminarily evaluate their mutagenicities.@*Methods@#In vitro cultured BRL 3A rat liver cells were treated with BPA, BPS, BPF and BPAF at concentrations of 0, 5, 10, 25, 50, 100, 150 and 200 μmol/L for 48 h, respectively. Then, the cell viability was determined using the CCK-8 assay, and the half maximal inhibitory concentration ( IC50 ) was calculated. The minimum inhibitory concentration for BRL 3A cell proliferation was screened, and the intracellular reactive oxygen species ( ROS ) was measured in BRL 3A cells using the 2',7'-dichlorodihydrofluorescein diacetate ( DCFH-DA ) assay. In addition, the effects of BPA, BPS, BPF and BPAF at concentrations of 1 000, 200, 40, 8 and 1.6 μg/plate on the mutant colonies of histidine-deficient Salmonella typhimurium ( TA1535, TA97a, TA98, TA100 and TA102 ) were tested using the Ames test.@*Results@#Treatment with BPA and BPF at concentrations of 100 to 200 μmol/L and with BPAF at concentrations of 25 to 200 μmol/L inhibited BRL 3A cell survival at a concentration-dependent manner, while exposure to BPS at concentrations of 5 to 200 μmol/L resulted in no changes in BRL 3A cell survival. The IC50 values of BPA, BPS, BPF and BPAF were 131.7, >200, 187.5 and 21.6 μmol/L against BRL 3A cells, respectively. Treatment with BPS at 100 μmol/L or BPAF at 25 μmol/L caused no significant changes in the ROS level; however, exposure to BPA at 100 μmol/L and BPF at 100 μmol/L significantly increased the ROS level. Ames test showed that BPA, BPS, BPF and BPAF did not induce mutagenicity in TA1535, TA97a, TA98, TA100 or TA102 strains.@*Conclusions@#BPAF shows the highest cytotoxicity to BRL 3A cells, and low-concentration exposure to BPS has few effects on BRL 3A cells. The cytotoxicity of bisphenols against BRL 3A cells may be associated with the induction of oxidative stress. None of the four bisphenols show mutagenic effects under the present experimental conditions.
ABSTRACT
OBJECTIVE:To conduct the abnormal toxicity test and study on the in vitro hemolytic reaction of Gluconate enoxa-cin injection,and provide reference for its safe use. METHODS:According to"Test for Abnormal Toxicity"in Chinese Pharmaco-poeia(2015 edition,Vol.Ⅱ),half lethal dose(LD50)of Gluconate enoxacin injection and setting of abnormal toxicity limit were carried out in mice. According to"Test for Haemolysis and Agglomeration"in Chinese Pharmacopoeia (2015 edition,Vol.Ⅱ), study for the in vitro hemolytic and agglomeration reaction was carried out in rabbits. RESULTS:The LD50 of Gluconate enoxacin injection for mice was 248.9 mg/kg;the setting limit of abnormal toxicity test was 28.4 mg/kg,and the results derived from the test using this limit met requirements. The haemolysis and agglomeration results derived from the test using clinical maximum con-centration(0.2 g/100 mL)met requirements. CONCLUSIONS:In order to reduce the clinical ADR and feasibility of ensuring quali-ty standard,the abnormal toxicity limit of Gluconate enoxacin injection should be set as 28.4 mg/kg.