Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 was cvaluated for its hepatotoxic effects in rats. The lyophilized cell extract injected intraperitoneally at 1 and 2 ...Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 was cvaluated for its hepatotoxic effects in rats. The lyophilized cell extract injected intraperitoneally at 1 and 2 LD50 (15.8 and 31.6 mg/kg, respectively) produced significant increase in liver-specific enzymes viz. plasma alkaline phosphatase,γ-glutamyl transferase, lactate dehydrogenase with a concomitant decrease in hepatic glutamic pyruvic transaminase. A corresponding increase in liver body weight index and histopathological changes in liver (degeneration of hepatocytes, congestion and hemorrhage etc.) are indicative of a dose and time dependent hepatotoxic nature of the algal extract展开更多
The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly ...The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly inhibited the growth of HeLa cells but had little effect on normal human kidney fibroblasts. With continuous exposure to Rh-123, the growth rate, colony forming ability, anl mitotic index of HeLa cells were decreased. The mechanism of toxicity of Rh-123 on HeLa cells was investigated by EM and enzyme cytochemistry stain. The mitochondria of carcinoma cells were the main targets for the inhibitory action of Rh-123, since they selectively accumulated the dye. At the dosage of Rh-123 which was toxic to HeLa cells, the structure and function of mitochondria were disrupted, as the mitochondria-related enzymes, i.e., ATPase, LDH and SDH were inhibited. The possible mechanism of the action of Rh-123 on HeLa cells is briefly discussed.展开更多
Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB agg...Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.展开更多
Gold nanoparticles,owing to their unique physicochemical and optical properties,well-established synthetic methods and easy modifications,have been widely used in biomedical science.Therefore,for their safe and effici...Gold nanoparticles,owing to their unique physicochemical and optical properties,well-established synthetic methods and easy modifications,have been widely used in biomedical science.Therefore,for their safe and efficient applications,much attention has been given to the toxicological evaluations of gold nanoparticles in biological systems.A large number of studies focusing on this problem have been carried out during the past years.However,the researches on gold nanoparticles toxicity still remain fragmentary and even contradictory with each other.This may be caused by the variety in experimental conditions.In this review,we aim to provide a better understanding about the in vitro and in vivo toxicity of gold nanoparticles by reviewing and describing the up to date literatures related to this problem and we mainly focused on these properties such as the particle size and shape,the surface charge and modification.Besides,we also summarized the adverse effect of gold nanoparticles on immune systems and analyzed the origin of the toxicity.展开更多
A number of species （organic and inorganic） in airborne particulates cause the toxicity to living being. The potential of in vitro test methods were explored for toxicity assessment of trace toxic elements （inorgan...A number of species （organic and inorganic） in airborne particulates cause the toxicity to living being. The potential of in vitro test methods were explored for toxicity assessment of trace toxic elements （inorganic species） present in ambient air on human being （lungs）. A year long sampling of airborne particles （PM2.5） was carded （April 2008 to March 2009） in Lahore, Pakistan. A total of thirty nine samples were collected on 47 mm Zefiuor Teflon filter membranes and each was analysed to characterize for the elements： Sb, As, Be, Cd, Cr, Co, Pb, Mn, Hg using ICP-MS in water extract and total acid digestate. The samples cytotoxicity was also established using lung derived cells and MTS colorimetric assays. This generated dose response curves and IC50 values for the elemental mixtures identified on the Teflon filter membrane. The results indicated that even at low concentrations airborne elemental mixtures displayed an additive toxic effect.展开更多
文摘Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 was cvaluated for its hepatotoxic effects in rats. The lyophilized cell extract injected intraperitoneally at 1 and 2 LD50 (15.8 and 31.6 mg/kg, respectively) produced significant increase in liver-specific enzymes viz. plasma alkaline phosphatase,γ-glutamyl transferase, lactate dehydrogenase with a concomitant decrease in hepatic glutamic pyruvic transaminase. A corresponding increase in liver body weight index and histopathological changes in liver (degeneration of hepatocytes, congestion and hemorrhage etc.) are indicative of a dose and time dependent hepatotoxic nature of the algal extract
文摘The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly inhibited the growth of HeLa cells but had little effect on normal human kidney fibroblasts. With continuous exposure to Rh-123, the growth rate, colony forming ability, anl mitotic index of HeLa cells were decreased. The mechanism of toxicity of Rh-123 on HeLa cells was investigated by EM and enzyme cytochemistry stain. The mitochondria of carcinoma cells were the main targets for the inhibitory action of Rh-123, since they selectively accumulated the dye. At the dosage of Rh-123 which was toxic to HeLa cells, the structure and function of mitochondria were disrupted, as the mitochondria-related enzymes, i.e., ATPase, LDH and SDH were inhibited. The possible mechanism of the action of Rh-123 on HeLa cells is briefly discussed.
基金financially supported by the Offi ce of Research and Standards, Office of Generic Drugs, CDER at the FDA (75F40120C00055)
文摘Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.
基金financially supported by the National Natural Science Foundation of China(No.31525009)Sichuan Innovative Research Team Program for Young Scientists(No.2016TD0004)
文摘Gold nanoparticles,owing to their unique physicochemical and optical properties,well-established synthetic methods and easy modifications,have been widely used in biomedical science.Therefore,for their safe and efficient applications,much attention has been given to the toxicological evaluations of gold nanoparticles in biological systems.A large number of studies focusing on this problem have been carried out during the past years.However,the researches on gold nanoparticles toxicity still remain fragmentary and even contradictory with each other.This may be caused by the variety in experimental conditions.In this review,we aim to provide a better understanding about the in vitro and in vivo toxicity of gold nanoparticles by reviewing and describing the up to date literatures related to this problem and we mainly focused on these properties such as the particle size and shape,the surface charge and modification.Besides,we also summarized the adverse effect of gold nanoparticles on immune systems and analyzed the origin of the toxicity.
文摘A number of species （organic and inorganic） in airborne particulates cause the toxicity to living being. The potential of in vitro test methods were explored for toxicity assessment of trace toxic elements （inorganic species） present in ambient air on human being （lungs）. A year long sampling of airborne particles （PM2.5） was carded （April 2008 to March 2009） in Lahore, Pakistan. A total of thirty nine samples were collected on 47 mm Zefiuor Teflon filter membranes and each was analysed to characterize for the elements： Sb, As, Be, Cd, Cr, Co, Pb, Mn, Hg using ICP-MS in water extract and total acid digestate. The samples cytotoxicity was also established using lung derived cells and MTS colorimetric assays. This generated dose response curves and IC50 values for the elemental mixtures identified on the Teflon filter membrane. The results indicated that even at low concentrations airborne elemental mixtures displayed an additive toxic effect.
