In Vivo Toxicity Evaluation of Sugar Adulterated Heterotrigona itama Honey Using Zebrafish Model

Honey is prone to be adulterated through mixing with sugars, cheap and low-quality honey, and other adulterants. Consumption of adulterated honey may cause several health issues such as weight gain, diabetes, and liver and kidney dysfunction. Therefore, studying the impact of consumption of adulterated honey on consumers is critical since there is a lack of study in this field. Hence, the aims of this paper were: (1) to determine the lethal concentration (LC50) of adulterated honey using zebrafish embryo, (2) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish, (3) to determine the effects of adulterated honey on histological changes of zebrafish, and (4) to screen the metabolites profile of adulterated honey by using zebrafish blood serum. The LC50 of Heterotrigona itama honey (acacia honey) and its sugar adulterants (light corn sugar, cane sugar, inverted sugar, and palm sugar in the proportion of 1–3% (w/w) from the total volume) was determined by the toxicological assessment of honey samples on zebrafish embryos (different exposure concentrations in 24, 48, 72, and 96 h postfertilization (hpf)). Pure H. itama honey represents the LC50 of 34.40 ± 1.84 (mg/mL) at 96 hpf, while the inverted sugar represents the lowest LC50 (5.03 ± 0.92 mg/mL) among sugar adulterants. The highest concentration (3%) of sugar adulterants were used to study the toxicology of adulterated honey using adult zebrafish in terms of acute, prolong-acute, and sub-acute tests. The results of the LD50 from the sub-acute toxicity test of pure H. itama honey was 2.33 ± 0.24 (mg/mL). The histological studies of internal organs showed a lesion in the liver, kidney, and spleen of adulterated treated-honey groups compared to the control group. Furthermore, the LC-MS/MS results revealed three endogenous metabolites in both the pure and adulterated honey treated groups, as follows: (1) S-Cysteinosuccinic acid, (2) 2,3-Diphosphoglyceric acid, and (3) Cysteinyl-Tyrosine. The results of this study demonstrated that adulterated honey caused mortality, which contributes to higher toxicity, and also suggested that the zebrafish toxicity test could be a standard method for assessing the potential toxicity of other hazardous food additives. The information gained from this research will permit an evaluation of the potential risk associated with the consumption of adulterated compared to pure honey.

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Adult Zebrafish Model for Screening Drug-Induced Kidney Injury

Toxicological Sciences ◽

10.1093/toxsci/kfaa009 ◽

2020 ◽

Vol 174 (2) ◽

pp. 241-253 ◽

Cited By ~ 3

Author(s):

Yuki Kato ◽

Yutaka Tonomura ◽

Hiroyuki Hanafusa ◽

Kyohei Nishimura ◽

Tamio Fukushima ◽

...

Keyword(s):

Predictive Value ◽

Safety Issue ◽

Kidney Injury ◽

Pathological Examination ◽

Control Group ◽

Adult Zebrafish ◽

Drug Induced ◽

Zebrafish Model ◽

Renal Tubular

Abstract Drug-induced kidney injury is a serious safety issue in drug development. In this study, we evaluated the usefulness of adult zebrafish as a small in vivo system for detecting drug-induced kidney injury. We first investigated the effects of typical nephrotoxicants, gentamicin and doxorubicin, on adult zebrafish. We found that gentamicin induced renal tubular necrosis with increased lysosome and myeloid bodies, and doxorubicin caused foot process fusion of glomerular podocytes. These findings were similar to those seen in mammals, suggesting a common pathogenesis. Second, to further evaluate the performance of the model in detecting drug-induced kidney injury, adult zebrafish were treated with 28 nephrotoxicants or 14 nonnephrotoxicants for up to 4 days, euthanized 24 h after the final treatment, and examined histopathologically. Sixteen of the 28 nephrotoxicants and none of the 14 nonnephrotoxicants caused drug-induced kidney injury in zebrafish (sensitivity, 57%; specificity, 100%; positive predictive value, 100%; negative predictive value, 54%). Finally, we explored genomic biomarker candidates using kidneys isolated from gentamicin- and cisplatin-treated zebrafish using microarray analysis and identified 3 candidate genes, egr1, atf3, and fos based on increased expression levels and biological implications. The expression of these genes was upregulated dose dependently in cisplatin-treated groups and was > 25-fold higher in gentamicin-treated than in the control group. In conclusion, these results suggest that the adult zebrafish has (1) similar nephrotoxic response to those of mammals, (2) considerable feasibility as an experimental model for toxicity studies, and (3) applicability to pathological examination and genomic biomarker evaluation in drug-induced kidney injury.

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The increase of blood creatinine levels and the gastric histopathology of rat after feeding of porang (Amorphophallus oncophyllus) flour treated with strobilantehes crispa

Jurnal Gizi dan Dietetik Indonesia (Indonesian Journal of Nutrition and Dietetics) ◽

10.21927/ijnd.2018.6(3).113-121 ◽

2019 ◽

Vol 6 (3) ◽

pp. 113

Author(s):

Ernawati Ernawati ◽

Veriani Aprilia ◽

Retno Pangastuti

Keyword(s):

Acute Toxicity ◽

Calcium Oxalate ◽

Rattus Norvegicus ◽

Toxicity Test ◽

Food Additives ◽

Test Group ◽

Control Group ◽

Acute Toxicity Test ◽

Blood Creatinine

ABSTRAKLatar belakang: Umbi Porang (Amorphophallus oncophyllus) meru[akan umbi asli Indonesia yang mengandung glucomannan. Glukomanan digunakan sebagai bahan tambahan makanan dan suplemen makanan bagi penderita diabetes, tekanan darah tinggi, konstipasi dan penurunan berat badan. Namun, umbi porang mengandung kalsium oksalat yang menyebabkan gatal jika dikonsumsi oleh karena itu kesiapan persiapan yang tepat. Perendaman dari S. crispa in vivo elah terbukti menurunkan kadar kalsium oksalat. Namun, kelebihan konsumsi kalsium oksalat dapat menyebabkan gangguan fungsi ginjal, terutama pada laju flomerasi glomerulus (GFR) dan mempengaruhi kerja ginjal, yaitu penyerapan dan kreatinin fltrasi.Tujuan: Untuk mengetahui pengaruh porang orang dengan S. crispa (keji beling) terhadap kreatinin darah dan histopatologi lambung tikus (Rattus norvegicus) Wistar pada uji toksisitas akut. Metode: Penelitian ini menggunakan experimental with one test group, without control group. Subjek 20 tikus Wistar betina putih (Rattus norvegicus) dengan berat 110-180 gram, usia 8 - 12 minggu, sehat, dan normal. Kelompok tikus dibagi menjadi Tepung Porang Murni (TPM) dan Tepung Porang dengan ekstrak etanol S. crispa (TPK). Setiap kelompok menggunakan dosis 2000 mg / kg berat badan (BW) dan 5000 mg / kgBB. Data kadar kreatinin dikumpulkan pada 24 dan 72 jam setelah makan juga dikonfirmasikan oleh tikus lambung. Analisis data menggunakan One-Way analysis of ariance (ANOVA).Hasil: Jenis larutan dan frekuensi perendaman tidak berpengaruh pada kadar kalsium oksalat padatepung porang, sedangkan lama perendaman tidak memberi efek. Kadar kreatinin darah tikus meningkat setelah pemberian pakan Tepung Porang urni (TPM) dan Tepung Porang dengan Ekstraksi Keji Beling (TPK) dengan dosis 5000 mg/kgBB.Kesimpulan: Pemberian tepung porang dengan perlakuan ekstrak S. crispa aman sampai dosis 5000 mg/kgBW. Ini terbukti dengan normalitas waktu di tingkat kadar kreatinin. KATA KUNCI: porang umbi, kalsium oksalat, rongga, kreatinin, uji toksisitas akut. ABSTRACTBackground: Porang (Amorphophallus oncophyllus) tuber is the original Indonesian tuber containing glucomannan. Glucomannan is utilized as food additives and food supplements for people who have problems with diabetes, high blood pressure, constipation and weight loss. However, it contains calcium oxalate which causes itchy if it is consumed therefore itness appropriate preparation. Soaking of S. crispa in vivo has proven lowering the levels of calcium oxalate. However, the excess consumption of oxalate calcium can cause renal function disorders, especially at the glomerular filtration rate (GFR) and affects the kidneys work, ie absorption and filtration creatinine.Objectives: The objective of this study is to know the influence of the porang flour with S. crispa (keji beling) on the level of blood creatinine and gastric histopathology of rats (Rattus norvegicus) Wistar on acute toxicity test.Methods: This research used experimental with one test group, without control group design. The subjects were 20 white female Wistar rats (Rattus norvegicus) with the weight of 110-180 grams, ages of 8 - 12 weeks, healthy, and normal. Rats were divided into. Native porang flour (TPM) and porang flour treated with ethanol extracts of S. crispa (TPK) groups. Each of groups used dosage of 2000 mg / kg body weight (BW) and 5000 mg/kgBW. Data of creatininee levels were collected at 24th and 72nd hours after feeding was also confirmed by gastric rats. The data analysis was used One-Way analysis of variance (ANOVA) .Results: The type of solution and the frequency of soaking had no effect on calcium oxalate levels in the Porang, whereas the length of soaking is not giving an effect. Blood levels of creatinine rats enhanced after feeding of TPM and TPK. At the dosage of 5000 mg/kgBW.Conclusions: The feeding of porang flour treated with S. crispa was safe until the dosage of 5000 mg/kgBW. It was proven by time normality in creatinine levels. KEYWORDS: porang tuber, calcium oxalate, cavity, creatinine, acute toxicity test.

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Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654150 ◽

1970 ◽

Vol 23 (02) ◽

pp. 386-404 ◽

Cited By ~ 6

Author(s):

G Müller-Berghaus ◽

H. G Lasch

Keyword(s):

Partial Thromboplastin Time ◽

Lethal Dose ◽

Control Group ◽

Factor V ◽

Consumption Coagulopathy ◽

Factor Activity ◽

Hageman Factor ◽

Intravascular Coagulation ◽

Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

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Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

International Journal of Molecular Sciences ◽

10.3390/ijms22031222 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1222

Author(s):

Cristina Cuello ◽

Cristina A. Martinez ◽

Josep M. Cambra ◽

Inmaculada Parrilla ◽

Heriberto Rodriguez-Martinez ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Analysis ◽

Survival Rates ◽

Control Group ◽

P Value ◽

Transcriptome Profile ◽

Embryo Viability ◽

The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

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Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1βas a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients

BioMed Research International ◽

10.1155/2015/812503 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Lukasz Markiewicz ◽

Dariusz Pytel ◽

Bartosz Mucha ◽

Katarzyna Szymanek ◽

Jerzy Szaflik ◽

...

Keyword(s):

Risk Factor ◽

Aqueous Humor ◽

Open Angle Glaucoma ◽

Luciferase Assay ◽

Control Group ◽

Promoter Regions ◽

Altered Expression ◽

Expression Levels ◽

The Impact

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.

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Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish

International Journal of Molecular Sciences ◽

10.3390/ijms19103195 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3195 ◽

Cited By ~ 17

Author(s):

Sreeja Sarasamma ◽

Gilbert Audira ◽

Stevhen Juniardi ◽

Bonifasius Sampurna ◽

Sung-Tzu Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Zinc Chloride ◽

Short Term Memory ◽

Amyloid Β ◽

Antioxidant Defense System ◽

Significant Inhibition ◽

Control Group ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Low Concentrations

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer’s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid β) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.

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Induction of Oxidative Stress and Apoptosis in the Injured Brain: Potential Relevance to Brain Regeneration in Zebrafish.

10.21203/rs.3.rs-549302/v1 ◽

2021 ◽

Author(s):

Surendra Kumar Anand ◽

Manas Ranjan Sahu ◽

Amal Chandra Mondal

Keyword(s):

Oxidative Stress ◽

Mrna Levels ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Stab Injury ◽

Zebrafish Brain ◽

Protein Levels ◽

Injured Brain ◽

Brain Regeneration ◽

The Impact

Abstract In the recent years, zebrafish, owing to its tremendous adult neurogenic capacity, has emerged as a useful vertebrate model to study brain regeneration. Recent findings suggest a significant role of the BDNF/TrkB signaling as a mediator of brain regeneration following a stab injury in the adult zebrafish brain. Since BDNF has been implicated in a plethora of physiological processes, we hypothesized that these processes are affected in the injured zebrafish brain. In this small study, we examined the indicators of oxidative stress and of apoptosis using biochemical assays, RT-PCR and IHC to reflect upon the impact of stab injury on oxidative stress levels and apoptosis in the injured adult zebafish brain. Our results indicate induction of oxidative stress in the injured adult zebrafish brain. Also, apoptosis was induced in the injured brain as indicated by increased protein levels of cleaved caspase3 as well as enhanced mRNA levels of both pro-apoptotic and anti-apoptotic genes. This knowledge contributes to the overall understanding of adult neurogenesis in the zebrafish model and raises new questions pertaining to the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

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Toxic Effects of TiO2 NPs on Zebrafish

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16040523 ◽

2019 ◽

Vol 16 (4) ◽

pp. 523 ◽

Cited By ~ 14

Author(s):

Tianle Tang ◽

Zhang Zhang ◽

Xiaopeng Zhu

Keyword(s):

Oxidative Damage ◽

Toxicity Test ◽

Titanium Dioxide Nanoparticles ◽

Toxic Effects ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Hatching Rate ◽

Adult Zebrafish ◽

Tio2 Nps

Titanium dioxide nanoparticles (TiO2 NPs) have become a widely used nanomaterial due to the photocatalytic activity and absorption of ultraviolet light of specific wavelengths. This study investigated the toxic effects of rutile TiO2 NPs on zebrafish by examining its embryos and adults. In the embryo acute toxicity test, exposure to 100 mg/L TiO2 NPs didn’t affect the hatching rate of zebrafish embryos, and there was no sign of deformity. In the adult toxicity test, the effects of TiO2 NPs on oxidative damage in liver, intestine and gill tissue were studied. Enzyme linked immunosorbent assay (ELISA) and fluorescence-based quantitative real-time reverse transcription PCR (qRT-PCR) were used to detect the three antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione S transferase (GSTs) in the above mentioned zebrafish organs at protein and gene levels. The results showed that long-term exposure to TiO2 NPs can cause oxidative damage to organisms; and compared with the control group, the activity of the three kinds of enzyme declined somewhat at the protein level. In addition, long-term exposure to TiO2 NPs could cause high expression of CAT, SOD and GSTs in three organs of adult zebrafish in order to counter the adverse reaction. The effects of long-term exposure to TiO2 NPs to adult zebrafish were more obvious in the liver and gill.

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Generic Vancomycin Enriches Resistant Subpopulations of Staphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05129-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 243-247 ◽

Cited By ~ 23

Author(s):

Carlos A. Rodriguez ◽

Maria Agudelo ◽

Andres F. Zuluaga ◽

Omar Vesga

Keyword(s):

Staphylococcus Aureus ◽

Population Analysis ◽

Recovery Process ◽

Control Group ◽

Infection Model ◽

Content Type ◽

Sterile Saline ◽

Generic Products ◽

The Impact

ABSTRACTPrevious studies have shown that “bioequivalent” generic products of vancomycin are less effectivein vivoagainstStaphylococcus aureusthan the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assessin vivothe impact of exposure to innovator and generic products of vancomycin onS. aureussusceptibility. A clinical methicillin-resistantS. aureus(MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log10CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies thanS. aureusATCC 29213 but without vancomycin-intermediateS. aureus(VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.

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In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

Human & Experimental Toxicology ◽

10.1177/0960327116685888 ◽

2017 ◽

Vol 36 (12) ◽

pp. 1270-1285 ◽

Cited By ~ 1

Author(s):

P Kumar ◽

D Swami ◽

DP Nagar ◽

KP Singh ◽

J Acharya ◽

...

Keyword(s):

Acute Toxicity ◽

Ache Activity ◽

Lethal Dose ◽

Acute Poisoning ◽

Control Group ◽

Swiss Albino Mice ◽

Albino Mice ◽

Brain Ache Activity ◽

Protection Index

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

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