Xiaoqing Guo - Academia.edu (original) (raw)
Papers by Xiaoqing Guo
Journal of Toxicology and Environmental Health, Part A
Mutagenesis
Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobac... more Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or a...
Journal of Toxicology and Environmental Health, Part B
Toxicological Research
The methods of applied genetic toxicology are changing from qualitative hazard identification to ... more The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machinegenerated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a twofold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.
Archives of toxicology, Jan 17, 2018
The Thymidine kinase (Tk) gene forward mutation assay, known as the mouse lymphoma assay (MLA), h... more The Thymidine kinase (Tk) gene forward mutation assay, known as the mouse lymphoma assay (MLA), has been widely used for evaluating the genotoxicity of chemical agents. A striking morphological feature of Tk mutant colonies is the bimodal distribution of their sizes, with cells from the large colonies growing at a normal rate and cells from the small colonies growing at a slower rate than normal. To understand the molecular distinction for the different growth rates, we performed whole genome sequencing (WGS) analysis of the large and small colony mutants generated from the MLA. Three large colony and three small colony mutants generated from cells treated with 4-nitroquinoline 1-oxide (4-NQO) or the vehicle control were selected for analysis. The WGS data were analyzed for loss of heterozygosity (LOH) and chromosome copy number along chromosome 11, where the Tk gene is located. Although there were LOH alterations in both large and small colony mutants, copy number changes near Tk l...
Toxicological sciences : an official journal of the Society of Toxicology, Jan 27, 2018
TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistr... more TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In the present study, we investigated and quantified the genotoxicity of four structurally similar nitroxides, TEMPO and three of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity. In addition, the four nitroxides caused DNA strand breakage. The mutagenicity and DNA damaging dose-responses of the test articles were compared using the PROAST benchmark dose (BMD) software package. The potency ranking of the four nitroxides for mutagenicity was different from the ranking...
Environmental and molecular mutagenesis, Jan 9, 2017
In vitro genotoxicity dose-response data have been investigated for their utility in modeling and... more In vitro genotoxicity dose-response data have been investigated for their utility in modeling and assessing potential differences in mutagenic responses between machine-generated whole smoke solutions (WSSs) from combusted cigarette tobacco products. Our previous study observed that potency ranking by benchmark dose (BMD) analysis was a useful modeling approach for quantitative assessment of differences between the mutagenicity of several structurally diverse chemical constituents of cigarette smoke. To follow-up on these observations, we used the mouse lymphoma assay (MLA) to evaluate the mutagenicity of WSSs prepared from two commercial cigarettes smoked under two different smoking machine regimens. L5178Y cells were exposed to ≥5 concentrations of each WSS for 4 hr ± S9 activation. S9 reduced the cytotoxicity and enhanced the mutagenicity of the WSSs. The resulting S9-mediated mutagenicity dose-responses were compared between test articles using BMD analysis, the lowest dose exce...
Archives of toxicology, Jan 9, 2017
4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitrox... more 4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitroxide radical and is generally used in organic and pharmaceutical syntheses for the oxidation of alcohols. Previously, we reported the involvement of reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) in TEMPO-induced apoptosis in mouse L5178Y cells. In this study, we investigated 4-methoxy-TEMPO induced toxicity in human HepG2 hepatoma cells and its underlying mechanisms. Treatments with 4-methoxy-TEMPO (0.5-5 mM for 2-6 h) caused oxidative stress as demonstrated by increased intensity of the ROS indicator H2DCF-DA, decreased levels of glutathione. 4-Methoxy-TEMPO treatment also induced DNA damage as characterized by increased levels of DNA tail intensity in the Comet assay, increased phosphorylation of related proteins including γ-H2A.X, p-Chk1, and p-Chk2, and activation of MAPK signaling pathways. In addition, 4-methoxy-TEMPO also induced autophagy as demonstrated by the ...
Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews, Jan 5, 2017
Ginkgo biloba has been used as a traditional herbal remedy for many thousand years and its leaf e... more Ginkgo biloba has been used as a traditional herbal remedy for many thousand years and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents. The National Toxicology Program conducted 2-year gavage studies and concluded that there was clear evidence of carcinogenic activity of Ginkgo biloba leaf extract in mice based on an increased incidence of hepatocellular carcinoma and hepatoblastoma. Recently, Ginkgo biloba leaf extract has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer. This review presents upda...
Nanotoxicology, Nov 21, 2016
The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxic... more The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having 3 different sizes and 2 different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA), and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronucleus from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materia...
Journal of applied toxicology : JAT, Feb 18, 2016
Verapamil is a Ca(2) (+) channel blocker and is highly prescribed as an anti-anginal, antiarrhyth... more Verapamil is a Ca(2) (+) channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca(2) (+) -permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mm ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mm ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca(2) (+) entry through L-type Ca(2) (+) channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca(2) (+) channels. Verapamil was more potent in attenuati...
Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews, Jan 17, 2016
The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in ... more The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects, of Aloe vera whole leaf extract, gel, and latex.
Scientific reports, Jan 30, 2015
Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a ... more Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage...
Methods in Pharmacology and Toxicology, 2013
Methods in Pharmacology and Toxicology, 2014
Chemico-biological interactions, Jan 13, 2015
The biological consequences of exposure to piperidine nitroxides is a concern, given their widesp... more The biological consequences of exposure to piperidine nitroxides is a concern, given their widespread use in manufacturing processes and their potential use in clinical applications. Our previous study reported that TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl), a low molecular weight free radical, possesses pro-oxidative activity in L5178Y cells. In this study, we investigated and characterized the role of reactive oxygen species (ROS) in TEMPO-induced toxicity in L5178Y cells. We found that TEMPO induced time- and concentration-dependent intracellular ROS production and glutathione depletion. TEMPO also induced apoptosis as demonstrated by increased caspase-3/7 activity, an increased proportion of annexin V stained cells, and decreased expression of anti-apoptotic proteins including Bcl-2, Bcl-xL and Mcl-1. N-acetylcysteine, a ROS scavenger, attenuated the ROS production and apoptosis induced by TEMPO. Moreover, Western blot analyses revealed that TEMPO activated γ-H2A.X, a hallmar...
Toxicol. Res., 2014
Both the Aloe vera whole leaf extract and decolorized whole leaf extract were mutagenic in cultur... more Both the Aloe vera whole leaf extract and decolorized whole leaf extract were mutagenic in cultured cells with different genetic damage.
Zhonghua zhong liu za zhi [Chinese journal of oncology], 2005
To investigate the clinical value of esophageal mucosal iodine stain during esophagoscopy for pat... more To investigate the clinical value of esophageal mucosal iodine stain during esophagoscopy for patients with early esophageal carcinoma or precancerous lesions without swallowing symptoms, through analyzing the correlation between endoscopic findings and pathological results of biopsy on the suspicious spots. For 366 patients examined by iodine stain during esophagoscopy, the position, size, shape and boundary of all visible unstained lesions were recorded and multiple biopsies were taken on the unstained spots. Before iodine stain, 462 lesions had been discovered in 366 patients. However, 478 abnormal lesions stained in 341 patients were detected after iodine stain, the remaining 25 gave no abnormal findings. More than 1/3 of patients were found to have more than 2 abnormally stained lesions. 28.4% of them (104 cases) had moderate or severe dysplasia or early esophageal cancer. The sensitivity of iodine stain in this series was 89.8%. Iodine stain is very useful in detecting occult ...
Neurotoxicology and Teratology, 2013
D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple ... more D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity. Published by Elsevier Inc.
Journal of Toxicology and Environmental Health, Part A
Mutagenesis
Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobac... more Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or a...
Journal of Toxicology and Environmental Health, Part B
Toxicological Research
The methods of applied genetic toxicology are changing from qualitative hazard identification to ... more The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machinegenerated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a twofold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.
Archives of toxicology, Jan 17, 2018
The Thymidine kinase (Tk) gene forward mutation assay, known as the mouse lymphoma assay (MLA), h... more The Thymidine kinase (Tk) gene forward mutation assay, known as the mouse lymphoma assay (MLA), has been widely used for evaluating the genotoxicity of chemical agents. A striking morphological feature of Tk mutant colonies is the bimodal distribution of their sizes, with cells from the large colonies growing at a normal rate and cells from the small colonies growing at a slower rate than normal. To understand the molecular distinction for the different growth rates, we performed whole genome sequencing (WGS) analysis of the large and small colony mutants generated from the MLA. Three large colony and three small colony mutants generated from cells treated with 4-nitroquinoline 1-oxide (4-NQO) or the vehicle control were selected for analysis. The WGS data were analyzed for loss of heterozygosity (LOH) and chromosome copy number along chromosome 11, where the Tk gene is located. Although there were LOH alterations in both large and small colony mutants, copy number changes near Tk l...
Toxicological sciences : an official journal of the Society of Toxicology, Jan 27, 2018
TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistr... more TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In the present study, we investigated and quantified the genotoxicity of four structurally similar nitroxides, TEMPO and three of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity. In addition, the four nitroxides caused DNA strand breakage. The mutagenicity and DNA damaging dose-responses of the test articles were compared using the PROAST benchmark dose (BMD) software package. The potency ranking of the four nitroxides for mutagenicity was different from the ranking...
Environmental and molecular mutagenesis, Jan 9, 2017
In vitro genotoxicity dose-response data have been investigated for their utility in modeling and... more In vitro genotoxicity dose-response data have been investigated for their utility in modeling and assessing potential differences in mutagenic responses between machine-generated whole smoke solutions (WSSs) from combusted cigarette tobacco products. Our previous study observed that potency ranking by benchmark dose (BMD) analysis was a useful modeling approach for quantitative assessment of differences between the mutagenicity of several structurally diverse chemical constituents of cigarette smoke. To follow-up on these observations, we used the mouse lymphoma assay (MLA) to evaluate the mutagenicity of WSSs prepared from two commercial cigarettes smoked under two different smoking machine regimens. L5178Y cells were exposed to ≥5 concentrations of each WSS for 4 hr ± S9 activation. S9 reduced the cytotoxicity and enhanced the mutagenicity of the WSSs. The resulting S9-mediated mutagenicity dose-responses were compared between test articles using BMD analysis, the lowest dose exce...
Archives of toxicology, Jan 9, 2017
4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitrox... more 4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitroxide radical and is generally used in organic and pharmaceutical syntheses for the oxidation of alcohols. Previously, we reported the involvement of reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) in TEMPO-induced apoptosis in mouse L5178Y cells. In this study, we investigated 4-methoxy-TEMPO induced toxicity in human HepG2 hepatoma cells and its underlying mechanisms. Treatments with 4-methoxy-TEMPO (0.5-5 mM for 2-6 h) caused oxidative stress as demonstrated by increased intensity of the ROS indicator H2DCF-DA, decreased levels of glutathione. 4-Methoxy-TEMPO treatment also induced DNA damage as characterized by increased levels of DNA tail intensity in the Comet assay, increased phosphorylation of related proteins including γ-H2A.X, p-Chk1, and p-Chk2, and activation of MAPK signaling pathways. In addition, 4-methoxy-TEMPO also induced autophagy as demonstrated by the ...
Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews, Jan 5, 2017
Ginkgo biloba has been used as a traditional herbal remedy for many thousand years and its leaf e... more Ginkgo biloba has been used as a traditional herbal remedy for many thousand years and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents. The National Toxicology Program conducted 2-year gavage studies and concluded that there was clear evidence of carcinogenic activity of Ginkgo biloba leaf extract in mice based on an increased incidence of hepatocellular carcinoma and hepatoblastoma. Recently, Ginkgo biloba leaf extract has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer. This review presents upda...
Nanotoxicology, Nov 21, 2016
The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxic... more The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having 3 different sizes and 2 different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA), and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronucleus from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materia...
Journal of applied toxicology : JAT, Feb 18, 2016
Verapamil is a Ca(2) (+) channel blocker and is highly prescribed as an anti-anginal, antiarrhyth... more Verapamil is a Ca(2) (+) channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca(2) (+) -permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mm ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mm ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca(2) (+) entry through L-type Ca(2) (+) channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca(2) (+) channels. Verapamil was more potent in attenuati...
Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews, Jan 17, 2016
The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in ... more The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects, of Aloe vera whole leaf extract, gel, and latex.
Scientific reports, Jan 30, 2015
Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a ... more Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage...
Methods in Pharmacology and Toxicology, 2013
Methods in Pharmacology and Toxicology, 2014
Chemico-biological interactions, Jan 13, 2015
The biological consequences of exposure to piperidine nitroxides is a concern, given their widesp... more The biological consequences of exposure to piperidine nitroxides is a concern, given their widespread use in manufacturing processes and their potential use in clinical applications. Our previous study reported that TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl), a low molecular weight free radical, possesses pro-oxidative activity in L5178Y cells. In this study, we investigated and characterized the role of reactive oxygen species (ROS) in TEMPO-induced toxicity in L5178Y cells. We found that TEMPO induced time- and concentration-dependent intracellular ROS production and glutathione depletion. TEMPO also induced apoptosis as demonstrated by increased caspase-3/7 activity, an increased proportion of annexin V stained cells, and decreased expression of anti-apoptotic proteins including Bcl-2, Bcl-xL and Mcl-1. N-acetylcysteine, a ROS scavenger, attenuated the ROS production and apoptosis induced by TEMPO. Moreover, Western blot analyses revealed that TEMPO activated γ-H2A.X, a hallmar...
Toxicol. Res., 2014
Both the Aloe vera whole leaf extract and decolorized whole leaf extract were mutagenic in cultur... more Both the Aloe vera whole leaf extract and decolorized whole leaf extract were mutagenic in cultured cells with different genetic damage.
Zhonghua zhong liu za zhi [Chinese journal of oncology], 2005
To investigate the clinical value of esophageal mucosal iodine stain during esophagoscopy for pat... more To investigate the clinical value of esophageal mucosal iodine stain during esophagoscopy for patients with early esophageal carcinoma or precancerous lesions without swallowing symptoms, through analyzing the correlation between endoscopic findings and pathological results of biopsy on the suspicious spots. For 366 patients examined by iodine stain during esophagoscopy, the position, size, shape and boundary of all visible unstained lesions were recorded and multiple biopsies were taken on the unstained spots. Before iodine stain, 462 lesions had been discovered in 366 patients. However, 478 abnormal lesions stained in 341 patients were detected after iodine stain, the remaining 25 gave no abnormal findings. More than 1/3 of patients were found to have more than 2 abnormally stained lesions. 28.4% of them (104 cases) had moderate or severe dysplasia or early esophageal cancer. The sensitivity of iodine stain in this series was 89.8%. Iodine stain is very useful in detecting occult ...
Neurotoxicology and Teratology, 2013
D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple ... more D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity. Published by Elsevier Inc.