scholarly journals Ciprofloxacin Enhances the Chemosensitivity of Cancer Cells to ABCB1 Substrates

2019 ◽  
Vol 20 (2) ◽  
pp. 268 ◽  
Author(s):  
Pranav Gupta ◽  
Hai-Ling Gao ◽  
Yunali Ashar ◽  
Nishant Karadkhelkar ◽  
Sabesan Yoganathan ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Hematological Malignancies ◽  
Scintillation Counter ◽  
Dependent Manner ◽  
Intracellular Accumulation ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Docking Analysis ◽  
Atpase Assay ◽  
Major Drug

ABCB1 is one of the major drug efflux transporters that is known to cause multidrug resistance (MDR) in cancer patients receiving chemotherapy for the treatment of solid tumors and hematological malignancies. Inhibition of ABCB1 efflux function is important for maintaining the intracellular concentration of chemotherapeutic drugs. Here, we evaluated ciprofloxacin for its ability to reverse MDR caused by the overexpression of ABCB1. Cytotoxicity of ciprofloxacin was determined by the MTT assay. The chemosensitizing effects of ciprofloxacin were determined in combination with ABCB1 substrates. The intracellular accumulation and efflux of ABCB1 substrates was measured by a scintillation counter, and protein expression was determined by the Western blotting. Vanadate-sensitive ATPase assay was performed to determine the effect of ciprofloxacin on the ATPase activity of ABCB1, and docking analysis was done to determine the interaction of ciprofloxacin with ABCB1. Ciprofloxacin significantly potentiated the cytotoxic effects of ABCB1 substrates in ABCB1-overexpressing cells. Furthermore, ciprofloxacin increased the intracellular accumulation and decreased the efflux of [3H]-paclitaxel without altering the expression of ABCB1. Ciprofloxacin stimulated the ATPase activity of ABCB1 in a concentration-dependent manner. Our findings showed that ciprofloxacin potently inhibits the ABCB1 efflux function and it has potential to be developed as a combination anticancer therapy.

scholarly journals Voruciclib, a Potent CDK4/6 Inhibitor, Antagonizes ABCB1 and ABCG2-Mediated Multi-Drug Resistance in Cancer Cells

2018 ◽  
Vol 45 (4) ◽  
pp. 1515-1528 ◽  
Author(s):  
Pranav Gupta ◽  
Yun-Kai Zhang ◽  
Xiao-Yu Zhang ◽  
Yi-Jun Wang ◽  
Kimberly W. Lu ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Cellular Localization ◽  
Intracellular Localization ◽  
Scintillation Counter ◽  
Flow Cytometric Analysis ◽  
Multi Drug Resistance ◽  
Dependent Manner ◽  
Cancer Drugs ◽  
Intracellular Accumulation ◽  
Anti Cancer

Background/Aims: The overexpression of ATP-Binding Cassette (ABC) transporters has known to be one of the major obstacles impeding the success of chemotherapy in drug resistant cancers. In this study, we evaluated voruciclib, a CDK 4/6 inhibitor, for its chemo-sensitizing activity in ABCB1- and ABCG2- overexpressing cells. Methods: Cytotoxicity and reversal effect of voruciclib was determined by MTT assay. The intracellular accumulation and efflux of ABCB1 and ABCG2 substrates were measured by scintillation counter. The effects on expression and intracellular localization of ABCB1 and ABCG2 proteins were determined by Western blotting and immunofluorescence, respectively. Vanadate-sensitive ATPase assay was done to determine the effect of voruciclib on the ATPase activity of ABCB1 and ABCG2. Flow cytometric analysis was done to determine the effect of voruciclib on apoptosis of ABCB1 and ABCG2-overexpressing cells and docking analysis was done to determine the interaction of voruciclib with ABCB1 and ACBG2 protein. Results: Voruciclib significantly potentiated the effect of paclitaxel and doxorubicin in ABCB1-overexpressing cells, as well as mitoxantrone and SN-38 in ABCG2-overexpressing cells. Voruciclib moderately sensitized ABCC10- overexpressing cells to paclitaxel, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, voruciclib increased the intracellular accumulation and decreased the efflux of substrate anti-cancer drugs from ABCB1- or ABCG2-overexpressing cells. However, voruciclib did not alter the expression or the sub-cellular localization of ABCB1 or ABCG2. Voruciclib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner. Lastly, voruciclib exhibited a drug-induced apoptotic effect in ABCB1- or ABCG2- overexpressing cells. Conclusion: Voruciclib is currently a phase I clinical trial drug. Our findings strongly support its potential use in combination with conventional anti-cancer drugs for cancer chemotherapy.

scholarly journals Modulatory Effect of Chelidonium majus Extract and Its Alkaloids on LPS-Stimulated Cytokine Secretion in Human Neutrophils

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 842 ◽  
Author(s):  
Sylwia Zielińska ◽  
Monika Ewa Czerwińska ◽  
Magdalena Dziągwa-Becker ◽  
Andrzej Dryś ◽  
Mariusz Kucharski ◽  
...  
Keyword(s):  
Biological Activities ◽  
Cytokine Secretion ◽  
Human Neutrophils ◽  
Root Extract ◽  
Dependent Manner ◽  
Chelidonium Majus ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Tnf Α ◽  
High Cytotoxicity

Due to certain differences in terms of molecular structure, isoquinoline alkaloids from Chelidonium majus engage in various biological activities. Apart from their well-documented antimicrobial potential, some phenanthridine and protoberberine derivatives as well as C. majus extract present with anti-inflammatory and cytotoxic effects. In this study, the LC–MS/MS method was used to determine alkaloids, phenolic acids, carboxylic acids, and hydroxybenzoic acids. We investigated five individually tested alkaloids (coptisine, berberine, chelidonine, chelerythrine, and sanguinarine) as well as C. majus root extract for their effect on the secretion of IL-1β, IL-8, and TNF-α in human polymorphonuclear leukocytes (neutrophils). Berberine, chelidonine, and chelerythrine significantly decreased the secretion of TNF-α in a concentration-dependent manner. Sanguinarine was found to be the most potent inhibitor of IL-1β secretion. However, the overproduction of IL-8 and TNF-α and a high cytotoxicity for these compounds were observed. Coptisine was highly cytotoxic and slightly decreased the secretion of the studied cytokines. The extract (1.25–12.5 μg/mL) increased cytokine secretion in a concentration-dependent manner, but an increase in cytotoxicity was also noted. The alkaloids were active at very low concentrations (0.625–2.5 μM), but their potential cytotoxic effects, except for chelidonine and chelerythrine, should not be ignored.

scholarly journals A Novel Synthetic Dihydroindeno[1,2-b] Indole Derivative (LS-2-3j) Reverses ABCB1- and ABCG2-Mediated Multidrug Resistance in Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3264 ◽  
Author(s):  
Chao Guo ◽  
Fangyuan Liu ◽  
Jie Qi ◽  
Jiahui Ma ◽  
Shiqi Lin ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Expression ◽  
Atpase Activity ◽  
Cancer Cells ◽  
Abc Transporter ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Expression Levels ◽  
Chemotherapy Drugs ◽  
Diphenyltetrazolium Bromide

10-oxo-5-(3-(pyrrolidin-1-yl) propyl)-5,10-dihydroindeno [1,2-b] indol-9-yl propionate (LS-2-3j) is a new chemically synthesized indole compound and some related analogues are known to be inhibitors (such as alectinib and Ko143) of ATP-binding cassette (ABC) transporters, especially the ABC transporter subfamily B member 1 (ABCB1) and the ABC transporter subfamily G member 2 (ABCG2). This study aimed to evaluate the multidrug resistance (MDR) reversal effects and associated mechanisms of LS-2-3j in drug-resistant cancer cells. The inhibition of cell proliferation in tested agents was evaluated by the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. Accumulation or efflux of chemotherapy drugs was analyzed by flow cytometry. The ATPase activity was measured using an ATPase activity assay kit. The mRNA transcripts and protein expression levels were detected by real-time PCR and Western blot, respectively. In this connection, LS-2-3j significantly enhanced the activity of chemotherapeutic drugs in MDR cells and could significantly increase the intracellular accumulation of doxorubicin (DOX) and mitoxantrone (MITX) by inhibiting the function of the efflux pumps in ABCB1- or ABCG2-overexpressing cells. Furthermore, reduced ATPase activity, mRNA transcription, and protein expression levels of ABCB1 and ABCG2 were observed in a concentration dependent manner in MDR cancer cells.

The mononucleotide-dependent, nonantisense mechanism of action of phosphodiester and phosphorothioate oligonucleotides depends upon the activity of an ecto-5′-nucleotidase

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 995-1002 ◽  
Author(s):  
Maria Koziolkiewicz ◽  
Edyta Gendaszewska ◽  
Maria Maszewska ◽  
C. A. Stein ◽  
Wojciech J. Stec
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Enzymatic Degradation ◽  
Umbilical Vein ◽  
Cell Types ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Specific Effects ◽  
Umbilical Vein Endothelial Cells

Many reports indicate different nonantisense yet sequence-specific effects of antisense phosphorothioate oligonucleotides. Products of enzymatic degradation of the oligonucleotides can also influence cell proliferation. The cytotoxic effects of deoxyribonucleoside-5′-phosphates (dNMPs) and their 5′-phosphorothioate analogs, deoxyribonucleoside-5′-monophosphorothioates (dNMPSs) on 4 human cell types (HeLa, HL-60, K-562, and endothelial cells) were examined, and the effects were correlated with the catabolism of these compounds. The results indicate that differences in cytotoxicity of dNMPs or dNMPSs in these cells depend upon different activity of an ecto-5′-nucleotidase. It has also been found that dNMPSs stimulate proliferation of human umbilical vein endothelial cells and HL-60 cells in a concentration-dependent manner. This stimulation might be caused by the binding of deoxynucleoside-5′-phosphorothioates to as-yet unidentified nucleotide receptor(s) at the cell surface.

scholarly journals Abyssinone V-4′ Methyl Ether, a Flavanone Isolated from Erythrina droogmansiana, Exhibits Cytotoxic Effects on Human Breast Cancer Cells by Induction of Apoptosis and Suppression of Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Stéphane Zingue ◽  
Abel Joël Gbaweng Yaya ◽  
Julia Cisilotto ◽  
Larissa Vanelle Kenmogne ◽  
Emmanuel Talla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Methyl Ether ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects

Abyssinone V-4′ methyl ether (AVME) isolated from Erythrina droogmansiana was recently reported to exhibit anti-mammary tumor effect in mice. The present work was therefore aimed at elucidating its cellular and molecular mechanisms. To achieve our goal, the cytotoxicity of AVME against tumoral and non-tumoral cell lines was evaluated by resazurin reduction test; flow cytometry allowed us to evaluate the cell cycle and mechanisms of cell death; the mitochondrial transmembrane potential, reactive oxygen species (ROS) levels, and caspase activities as well as apoptosis-regulatory proteins (Bcl-2 and Bcl-XL) were measured in MDA-MB-231 cells. Further, the antimetastatic potential of AVME was evaluated by invasion assay. AVME exhibited cytotoxic effects in all tested tumor cell lines and induced a significant increase in the percentage of MDA-MB-231 cells at G2/M and S phases of the cell cycle in a concentration-dependent manner. AVME also induced apoptosis in MDA-MB-231 cells, which was accompanied by the activation of caspase-3 and caspase-9 and downregulation of Bcl-2 and Bcl-XL proteins. Moreover, AVME suppressed cancer cell invasion by the inhibition of the metalloproteinase-9 activity. Findings from this study suggest that AVME has anti-breast cancer activities expressed through mitochondrial proapoptotic pathway including impairment of aggressive behaviors of breast cancer cells.

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

1988 ◽  
Vol 255 (4) ◽  
pp. F666-F673 ◽  
Author(s):  
I. Seri ◽  
B. C. Kone ◽  
S. R. Gullans ◽  
A. Aperia ◽  
B. M. Brenner ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Active Agent ◽  
Sodium Concentration ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Maximal Inhibition ◽  
Concentration Dependent Manner ◽  
Order Of Magnitude ◽  
Tubule Cells ◽  
Dopa Concentration

Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Polylysine activates smooth muscle myosin ATPase activity via induction of a 10S to 6S transition

1993 ◽  
Vol 265 (2) ◽  
pp. C379-C386 ◽  
Author(s):  
P. T. Szymanski ◽  
D. G. Ferguson ◽  
R. J. Paul
Keyword(s):  
Smooth Muscle ◽  
Atpase Activity ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Atpase ◽  
Solution Viscosity ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Myosin Atpase Activity ◽  
Muscle Myosin

Polylysine (10-13 kDa) stimulates contraction in smooth muscle skinned fibers and activates actomyosin adenosinetriphosphatase (ATPase) activity in the absence of myosin light chain phosphorylation [P. T. Szymanski and R. J. Paul. Adv. Exp. Med. 304: 363-368, 1991; P. T. Szymanski, J. D. Strauss, G. Doerman, J. DiSalvo, and R. J. Paul. Am J. Physiol. 262 (Cell Physiol. 31): C1445-C1455, 1992]. To provide further information on the mechanism of polylysine action on contractility in smooth muscle, we investigated its effect on ATPase activity and conformation of purified gizzard myosin. We report here that polylysine directly stimulates myosin ATPase activity in a concentration-dependent manner. This stimulation could be completely abolished with the addition of heparin, a negatively charged heteropolysaccharide. Polylysine (10 microM) increases myosin ATPase activity to a level similar to that of myosin phosphorylation. Addition of 10 microM polylysine to phosphorylated myosin [with myosin light chain kinase and adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), to approximately 1.9 mol P/mol myosin], however, did not further stimulate ATPase activity. At 0.2 M KCl (the salt concentration at which myosin exists primary in the 10S form), the addition of polylysine increases myosin ATPase activity to a level comparable to that of untreated myosin in 0.3 M KCl. These changes parallel the increase in solution viscosity elicited by polylysine. These results suggest that polylysine induces a transition in myosin conformation from the 10S to the 6S form, and this was confirmed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqi Yang ◽  
Zhuo-Xun Wu ◽  
Jing-Quan Wang ◽  
Qiu-Xu Teng ◽  
Zi-Ning Lei ◽  
...  
Keyword(s):  
Pharmacokinetic Profile ◽  
Binding Pocket ◽  
Inhibitory Effect ◽  
Drug Binding ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Cell Viability Assay ◽  
Concentration Dependent Manner ◽  
Viability Assay ◽  
Atpase Assay

OTS964 is a potent T-LAK cell-originated protein kinase (TOPK) inhibitor. Herein, we investigated the interaction of OTS964 and multidrug resistance (MDR)-associated ATP-binding cassette sub-family G member 2 (ABCG2). The cell viability assay indicated that the effect of OTS964 is limited in cancer drug-resistant and transfected cells overexpressing ABCG2. We found that the known ABCG2 transporter inhibitor has the ability to sensitize ABCG2-overexpressing cells to OTS964. In mechanism-based studies, OTS964 shows inhibitory effect on the efflux function mediated by ABCG2, and in turn, affects the pharmacokinetic profile of other ABCG2 substrate-drugs. Furthermore, OTS964 upregulates ABCG2 protein expression, resulting in enhanced resistance to ABCG2 substrate-drugs. The ATPase assay demonstrated that OTS964 stimulates ATPase activity of ABCG2 in a concentration-dependent manner. The computational molecular docking analysis combined with results from ATPase assay suggested that OTS964 interacts with drug-binding pocket of ABCG2 and has substrate-like behaviors. Thus, OTS964 is an MDR-susceptible agent due to its interactions with ABCG2, and overexpression of ABCG2 transporter may attenuate its therapeutic effect in cancer cells.

scholarly journals Application of Electric Cell-Substrate Impedance Sensing to Investigate the Cytotoxic Effects of Andrographolide on U-87 MG Glioblastoma Cell Migration and Apoptosis

Sensors ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 2275 ◽  
Author(s):  
Sheng-Po Chiu ◽  
Buyandelger Batsaikhan ◽  
Huei-Mei Huang ◽  
Jia-Yi Wang
Keyword(s):  
Cell Migration ◽  
Western Blotting ◽  
Primary Brain Tumor ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Impedance Sensing ◽  
Cell Substrate ◽  
Related Proteins

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. In recent studies, the efficacy of suberoylanilide hydroxamic acid (SAHA) has been investigated for GBM. We explored the effects of two exploratory compounds, the histone deacetylase SAHA and the natural product andrographolide, on Uppsala 87 Malignant Glioma (U-87 MG) cell migration and viability in comparison with the clinically used therapeutic agent temozolomide (TMZ). We used the electric cell–substrate impedance sensing (ECIS) system to monitor the migration of U-87 MG cells after treatment with various concentrations of these compounds. Moreover, we used the Alamar blue assay and western blotting to observe the concentration-dependent changes in the viability and apoptosis of U-87 MG cells. Our results demonstrated that both SAHA and andrographolide (10–300 μM) significantly inhibited GBM cell migration in a concentration-dependent manner, and 10 μM SAHA and 56 μM andrographolide demonstrated remarkable inhibitory effects on U-87 MG migration. Western blotting indicated that compared with TMZ, both SAHA and andrographolide induced higher expression levels of apoptosis-related proteins, such as caspase-3, BAX, and PARP in U-87 MG cells. Furthermore, all three drugs downregulated the expression of the antiapoptotic protein Bcl-2. In conclusion, SAHA and andrographolide showed exceptional results in inhibiting cell migration and motility. The ECIS wound healing assay is a powerful technique to identify and screen potential therapeutic agents that can inhibit cancer cell migration.

scholarly journals An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (Naja atra) Venom by Different Antivenoms

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 377 ◽  
Author(s):  
Qing Liang ◽  
Tam Minh Huynh ◽  
Nicki Konstantakopoulos ◽  
Geoffrey K. Isbister ◽  
Wayne C. Hodgson
Keyword(s):  
Southern China ◽  
In Vitro Toxicity ◽  
Dependent Manner ◽  
Muscle Preparation ◽  
Concentration Dependent Manner ◽  
Cytotoxic Effects ◽  
Contractile Responses ◽  
Nerve Muscle ◽  
Naja Atra

The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of N. atra venom, as well as examining the efficacy of three Chinese monovalent antivenoms (N. atra antivenom, Gloydius brevicaudus antivenom and Deinagkistrodon acutus antivenom) and an Australian polyvalent snake antivenom. In the chick biventer cervicis nerve-muscle preparation, N. atra venom (1–10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese N. atra antivenom (0.75 U/mL) or Australian polyvalent snake antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese antivenom (0.75 U/mL) or Australian polyvalent antivenom (3 U/mL) at the t90 time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. N. atra antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, G. brevicaudus antivenom (24 U/mL), D. acutus antivenom (8 U/mL) and Australian polyvalent snake antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, N. atra venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC50) of 2.8 ± 0.48 μg/mL. N. atra antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent snake antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither G. brevicaudus antivenom or D. acutus antivenom were able to prevent the cytotoxicity. This study indicates that Chinese N. atra monovalent antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of N. atra venom but the clinical effectiveness of the antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper antivenoms (i.e., G. brevicaudus and D. acutus antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study.

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