Acute Oral Toxicity Study Research Articles

Isolation, preparation and investigation of leaf extracts of Aloe barbadensis for its remedial effects on tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) by in vivo and in silico approaches in experimental rats.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

GC-MS profiling and evaluation of acute oral toxicity, anti-tumour, antimicrobial and antioxidant activities of Croton socotranus Balf.f. aerial parts: in-vitro, in-vivo and in-silico studies

Croton socotranus Balf.f. shrub is widely used traditionally in Asia as an anti-infective. The study was conducted for metabolite profiling, oral acute toxicity and antioxidant studies, antimicrobial activity and anticancer effect against human hepatoma (HepG2), breast cancer (MCF-7) and rhabdomyosarcoma (RD) cells. Gas chromatography-mass spectrometry analysis revealed the presence of 39 compounds, predominantly comprising fatty acids (57.76%), sesquiterpenes (24.56%) and triterpenes (9.54%). The n-hexane fraction exhibited promising antimicrobial activity and displayed a potent anti-tumour effect against HepG2, MCF-7 and RD cells with IC50 values of 3.4, 6.5 and 7.1 μg/mL, respectively. Histological examination revealed significant morphological changes consistent with the changes observed in the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with phosphoinositide 3-kinase and poly(ADP-ribose)polymerase-1 enzymes. Our findings suggest the potential of C. socotranus as a valuable source of antimicrobial and anticancer agents.

Assessment of Safety Profile of Activated Curcumin C3 Complex (AC3®), Enriched Extract of Bisdemethoxycurcumin from the Rhizomes of Curcuma longa.

The present work was carried out to investigate the toxic effects of Activated Curcumin C3 Complex (AC3®) through the methods of acute, subacute, subchronic, reproductive/developmental toxicity, and genotoxicity when administered orally in experimental rodents. The studies were carried out in line with OECD principles of good laboratory practice. A single-dose acute oral toxicity study was conducted on female Wistar rats that produced no toxic effects after 14 days (the observation period) of treatment. Subacute, subchronic, and reproductive/developmental studies were conducted in Wistar rats, divided equally into vehicle control, 125, 250, and 500 mg/kg dose groups along with recovery groups for vehicle control and high dose. In all the studies, there were no abnormal clinical signs/behavioral changes, reproductive and developmental parameters, or gross and histopathological changes. Likewise, no alteration was found in the body weight, hematology, and other biochemical parameters. Also, it did not show mutagenicity in the in vitro AMES test or clastogenicity and aneugenicity in the in vivo micronucleus test, indicating that AC3® did not induce any genotoxic effects. This revealed that oral administration of AC3® is safe in rodents, nonmutagenic, and had no observed adverse effects under experimental conditions.

Efficacy of Acute Oral Supplementation of Aquilaria malaccensis Leaves Aqueous Extract on Adult Female Sprague Dawley Rat Growth Performance

Aquilaria malaccensis belongs to the Thymelaceae family and is frequently encountered in select states of Peninsular Malaysia, notably Terengganu, Kelantan, Pahang, and Johor. Its favorable pharmacological and nutritional attributes have attracted the attention of experts in the pharmaceutical and food industries. They are currently investigating its potential as an organic substitute herb for the formulation of diverse medicinal commodities. In spite of its growing utilization as a supplementary component, it is crucial to acknowledge that improper or excessive consumption of Aquilaria malaccensis leaf extract might pose a risk of oral toxicity. To evaluate this aspect, an acute study was carried out to investigate both the immediate and delayed toxic repercussions of aqueous extract from Aquilaria malaccensis leaves on rats during a 14-day span.The study involved twenty-four female Sprague Dawley rats, divided into four groups: Control (C); 1 ml of distilled water, Treatment 1 (T1); 1 g of Aquilaria malaccensis per kg of body weight, Treatment 2 (T2); 2 g per kg of body weight, and Treatment 3 (T3); 3 g per kg of body weight. The data were analyzed using appropriate statistical methods; one-way analysis of variance (ANOVA) for parametric data and the Chi-Square test for non-parametric data.The results indicated that both T2 and T3 led to a significant increase in the mean weight of the organ (i.e.,ovary) compared to the control group. However, no significant differences were observed among the treatment groups with regard to weekly food intake (WFI), feed conversion ratio (FCR), and body weight gain (BWG) throughout the 14-day acute oral toxicity assessment. In conclusion, this preliminary study involving female rats suggests that doses of Aquilaria malaccensis up to 3 g/kg of body weight do not result in immediate (within 3-4 hours) or delayed toxic effects over a 14-day period, as evidenced by behavioral and physical, and growth parameter assessments (weekly food intake (WFI), feed conversion ratio (FCR), and body weight gain (BWG). The study indicates that exposing the animals to Aquilaria malaccensis aqueous extract at doses of 1 g, 2 g, and 3 g/kg of body weight does not adversely affect their overall condition. No instances of mortality or severe clinical effects were observed in any of the female rats during this acute oral toxicity study.

Evaluation of an in vitro experimental platform of human polarized intestinal epithelial monolayers for the hazard assessment of insecticidal proteins

Previous work demonstrated the utility of using human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on Transwell® filters to differentiate between hazardous and non-hazardous proteins. The current study seeks to further resolve appropriate concentrations for evaluating proteins of unknown hazard potential using the IEC experimental platform and leverages these parameters for evaluating the potential toxicity of insecticidal proteins characteristic of those expressed in genetically modified (GM) agricultural biotechnology crops. To establish optimal test protein concentrations, effects of several known hazardous (C. perfringens epsilon toxin, Listeriolysin O, Phaseolus vulgaris erythroagglutinin, E. coli Shiga toxin 1, C. difficile Toxin B and wheat germ agglutinin) and non-hazardous (Ara-h2, β-lactoglobulin, fibronectin and Rubisco) proteins on IEC barrier integrity and cell viability were evaluated at concentration ranges. Two insecticidal proteins (AfIP-1A and AfIP–1B) were evaluated for effects in the IEC assay, a seven-day insecticidal bioassay, and assessed in a high-dose 14-day acute oral toxicity study in mice. The results obtained from the human in vitro IEC assay were consistent with results obtained from an in vivo acute oral toxicity study, both demonstrating that the combination of AfIP-1A and AfIP–1B do not exhibit any identifiable harmful impacts on mammalian cells.

New supporting data to guide the use of evident toxicity in acute oral toxicity studies (OECD TG 420)

Currently there are three test guidelines (TG) for acute oral toxicity studies of substances or mixtures from the Organisation for Economic Co-operation and Development (OECD). TG 423 and TG 425 use lethality as an endpoint, while TG 420 replaces death with ‘evident toxicity’, defined as clear signs that exposure to a higher dose would result in death. However, the perceived subjectivity of ‘evident toxicity’ may be preventing wider use of TG 420. To address this, the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the European Partnership for Alternative Approaches to Animal Testing (EPAA) collaborated to provide recommendations on the recognition of ‘evident toxicity’. Historical data from acute oral toxicity studies were analysed for clinical signs at the lower dose that could have predicted death at the higher dose. Several signs including ataxia, laboured respiration, and eyes partially closed, alone or in combination, are highly predictive. Others such as lethargy, decreased respiration, and loose faeces have lower but still appreciable positive predictive value (PPV). The data has been used to develop recommendations to promote use of TG 420 and thus reduce the suffering and numbers of animals used in acute oral toxicity studies.

Evaluation of Cassia fistula seed galactomannan as tablet-binder in formulation of diclofenac sodium-loaded monolithic matrix tablet

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder.

Toxicological Evaluation of <i>Vaisvanara churna</i> an Ayurvedic Formulation

Vaisvanara churna an ayurvedic formulation was screened for its toxicity profile. The study was carried out based on CCRAS Protocols. For the acute oral toxicity study, Group I served as vehicle control, Vaisvanara churna at a single oral dose of 6500 mg/kg b.w., was administered to 5 male and 5 female Swiss albino mice (Group II) and observed for 14 consecutive days for clinical signs, body weight and mortality. For 90 days repeated dose toxicity study eighty animals (40 male and 40 female) were distributed into four groups. Group I served as vehicle control. Groups II, III, and IV were administered with 450, 2250 and 4500 mg/kg b.w., respectively for 90 days orally. During this period, feed intake, body weight, signs of toxicity, haematological and biochemical parameters were recorded at periodical intervals. After 90 days animals were sacrificed for necropsy, vital organs were weighed and preserved for histopathological analysis. In an acute toxicity study, a single dose of Vaisvanara churna at 6500 mg/kg b.w., caused no mortality in animals, suggesting that the median lethal dose is greater than 6500 mg/kg b.w. In 90-day, repeated dose toxicity study, administration of Vaisvanara churna for 90 days, up to 4500 mg/kg b.w., caused no significant changes in body weights or organ weights of rats in the treated groups when compared with the control group. In addition, haematological and biochemical parameters were within the physiological limits. Histopathological analysis revealed no signs of degeneration. These results showed that Vaisvanara churna is apparently safe as indicated therapeutically for long-term administration for chronic ailments.

Exploration of the anti-diabetic potential of hydro-ethanolic leaf extract of Koenigia polystachya L.: an edible wild plant from Northeastern India

BackgroundGlobally, medicinal plants are used to treat diseases like diabetes. The present study evaluates the possible antioxidant, acute oral toxicity, the in-vitro and in-vivo antidiabetic potential of the hydro-ethanolic leaf extract of Koenigia polystachya (HELeKP) against beta-cell damage in experimentally induced diabetes mellitus. The DPPH (2,2-diphenyl-1-picrylhydrazine), ABTS [2,2′-azino bis-(3-ethylbenzothiazoline-6-sulfonic acid)], H2O2 (Hydrogen peroxide), superoxide radical scavenging activity and NO (Nitric oxide) assay estimated the in-vitro antioxidant assay of HELeKP. The acute oral toxicity study was evaluated per the OECD (Organization for Economic Cooperation and Development) test guidelines 425. Diabetes was stimulated in rats with a single dose of Streptozotocin (STZ), and after confirmation of diabetes, HELeKP was given orally for 21 days. Blood/serum samples were gathered and examined for biochemical changes, while tissue samples were evaluated for histopathological alterations.ResultsThe IC50 value of the HELeKP for all the anti-oxidant assays confirms the free radical scavenging activity. The data on acute oral toxicity revealed that the HELeKP used in the study was comparatively very safe. The outcomes of the in-vivo study suggested that the extract significantly reduced (p < 0.001) the fasting glucose level in STZ-induced diabetic rats. Furthermore, the lipid profile level was significantly normalized (p < 0.01, p < 0.001) in diabetic rats. The histopathological observation of the pancreas in HELeKP-treated rats showed significant beta-cell restoration.ConclusionsBased on the outcomes of this study, the HELeKP-treated rats have significant free radical scavenging and anti-diabetic potential. Therefore, it can be recommended as a beneficial functional vegetable for consumption.

Phytochemical Screening and Acute Oral Toxicity Studies of Seeds of Hyptis Suaveolens and Fruits of Coccinia Grandis.

Hyptis suaveolens, a member of the Lamiaceae family, is traditionally used as a carminative and an expectorant. It is also found to haveanti-inflammatory, antimicrobial, and anti-cancer potential. Coccinia grandis, a member of the Cucurbitaceae family, is found to be anti-helminthic,antioxidant, anti-ulcer, anti-malarial, anti-inflammatory, antipyretic, analgesic, antifungal, antitussive and hypoglycemic in different animal models.The objective of the present study is intended to focus on the phytochemical evaluation of Hyptis suaveolens seeds and Coccinia grandis fruits andto study their toxic effects by acute oral toxicity study and establish the safety category of these extracts as per organization for economiccooperation and development (OECD-TG-423) guidelines and GHS classification system. Hyptis suaveolens seeds, and Coccinia grandis fruits werecollected, and the extraction was made and stored for phytochemical analysis. The extract was tested for phytochemical constituents like alkaloids,phenol, flavonoids, carbohydrates, triterpenes, sterols, saponins, and tannins. In an acute oral toxicity study, the hydroalcoholic extracts of bothplants were administered orally at a dose of 2000mg/Kg b.w. to the three rats in each group in Step I of the individual group. They were observedfor 48 hrs and followed for 14 days (step II). They were examined for sensory, physiological, and behavioral parameters and signs of toxicity andmortality. The phytochemical study revealed the presence of many pharmacologically active constituents, and the acute oral toxicity study showedno changes in physical, sensory, physiological, or behavioral parameters, with all animals remaining healthy and active. There were no signs ofmortality or moribund status in both step I and II. The results indicate that the hydroalcoholic extracts of Hyptis suaveolens seeds and Cocciniagrandis fruits fall under category '5' or 'unclassified' of the GHS system, allowing them to be used safely in pharmaceutical formulations fortherapeutic use.

A REVIEW ON ACUTE AND SUBACUTE ORAL TOXICITY STUDIES OF SNUHI (EUPHORBIA NERIIFOLIA LINN.)

(Euphorbia neriifolia Linn.) is included in Upavisha as per Ayurvedic classics, and according to modern toxicology, it is classified as irritant organic vegetable poison. It is an active ingredient of many Ayurvedic formulations like Chitrakadi taila, Jatyadi varti, Snuhi kshara etc. These formulations are widely used to treat disease conditions like Shotha (Edema), Dushivisha, Aamdosha, etc. Before administering any potential drug to humans, it is essential to evaluate its safety in animals to define safe human doses through validated scientific toxicity studies. Hence, there is a need to conduct toxicity studies of Snuhi and its phytoconstituents in various extract forms to recognise its safety from the perspective of the Globally Harmonised Classification System. In this article, a special emphasis is done on gathering details on acute and subacute oral toxicity studies of Snuhi (Euphorbia neriifolia Linn.)

OECD GUIDELINES FOR ACUTE ORAL TOXICITY STUDIES: AN OVERVIEW

The OECD Guidelines for testing chemicals provide a unique method for assessing the potential impact of chemicals on human health and the environment. These are divided into five sections. Oral toxicity studies are mentioned in the fourth section, i.e. Health Effects. This section cites the guidelines for acute, sub-acute, sub-chronic and chronic oral toxicity studies. Acute oral toxicity refers to those adverse effects of oral administration of a single dose or multiple doses given within 24 hours. OECD guidelines for Acute oral toxicity include 420 (Fixed Dose Procedure), 423 (Acute Toxic Class Method) and 425 (Up-and-Down procedure). OECD guidelines 420, 423 and 425 provide information on the hazardous properties and allow the substance to be ranked and classified according to the Globally Harmonised System (GHS) for the classification of chemicals which cause acute toxicity. In OECD Guideline 423, the method classifies the test substance as one of a series of toxicity classes defined by fixed LD50 cut-off values, while the OECD Guideline 425 method permits estimation of LD50 with a confidence interval. Based on these guidelines, a toxic dose of the drug is obtained. This study aims to compare and highlight the acute oral toxicity guidelines.

Herbal formulation: Constac plus granules for severe constipation; an acute oral toxicity study

The main aim of this study was to evaluate the acute oral toxicity of Constac® Plus granules. Twelve rats were randomized into four groups of three at random. Groups 2 and 3 received doses of 2000 mg/kg body weight of Constac Plus granules, while group 4 received doses of 5000 mg/kg body weight of Constac Plus granules. Group 1 served as the control and merely received distilled water. For 14 days, the rats were closely monitored for any indications of toxicity. At the end of the study, all rats underwent necropsy and gross pathology was noted. The results demonstrated that during the 14-day observation period, none of the rats in the control or treatment groups showed any clinical symptoms of toxicity or mortality. It was determined that the LD50 value was more than 5000 mg/kg body weight. The acute oral toxicity study of Constac Plus granules in wistar rats concluded that there was no toxicity at dosages up to 5000 mg/kg body weight. These results proved that the usage of Constac Plus granules administered orally is safe.

Screening the Extract of Laportea bulbifera (Sieb. et Zucc.) Wedd. Based on Active Component Content, Its Antioxidant Capacity and Exploration of Hepatoprotective Activity in Rats.

Laportea bulbifera (Sieb. et Zucc.) Wedd., a plant with a long history of medicinal use, possesses uncertainly defined medicament portions while its antioxidant capacity remains largely unexplored. To gain a better understanding of its medicinal value, this study focused on investigating the Laportea bulbifera aboveground part (LBAP) and the Laportea bulbifera root (LBR). Through an assessment of the bioactive compound content, a significant finding emerged: the LBR exhibited notably higher levels of these bioactive phytochemicals compared to the LBAP. This observation was further reinforced by the antioxidant assays, which demonstrated the superiority of the LBR's antioxidant capacity. The experimental results unequivocally indicate that the root is the optimal medicament portion for Laportea bulbifera. Furthermore, it was discovered that the presence of alcohol in the extraction solvent significantly enhanced the extraction of active ingredients, with the methanol extract of LBR performing the best among the extracts tested. Consequently, this extract was selected for further research. Leveraging cutting-edge UHPLC-ESI-Q-TOF-MS technology, the methanol extract of LBR was meticulously analyzed, revealing the presence of 41 compounds, primarily belonging to the phenolics and fatty acids. Remarkably, stability experiments demonstrated that the phenolics in the methanol extract maintained their stability across various pH values and during in vitro simulations of the human digestive system, albeit showing gradual degradation under high temperatures. Furthermore, the oxidative stability tests conducted on oils revealed the potential of the methanol extract as a stabilizer for olive oil and sunflower oil. Moreover, oral acute toxicity studies confirmed the low toxicity of the methanol extract, further supporting its safe use for medicinal purposes. Of particular note, histopathological examination and biochemical analysis affirmed the remarkable protective effects of the methanol extract against d-galactosamine-induced liver damage. These findings underscore the therapeutic potential of the methanol extract from the LBR in the treatment of diseases associated with oxidative imbalance.

Green synthesis of quince/pectin cross-linked superporous hydrogel sponges for pH-regulated sustained domperidone delivery

The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of domperidone. The designed hydrogel sponges were evaluated for a sol–gel fraction (%), swelling studies and kinetics, drug loading (%), electrolyte-responsive character, scanning electron microscopy (SEM), thermal analysis, drug-excipient compatibility studies (FTIR), X-ray diffraction (XRD) analysis, mechanical testing, in-vitro drug release studies, and acute oral toxicity studies. The drug loading (%) ranged from 67 to 85%. Hydrogel sponges displayed pH-responsive swelling potential, with optimum swelling in a phosphate buffer (pH 7.4) and insignificant swelling in an acidic buffer of pH 1.2. The prepared hydrogel sponges displayed second-order swelling dynamics. The FTIR data revealed the successful fabrication of the hydrogel sponges with the primary drug peaks remaining unchanged, demonstrating excipients-drug compatibility. SEM confirmed the rough, porous surface of hydrogel sponges with numerous cracks. XRD measurements revealed the transformation of the crystalline nature of domperidone into an amorphous one within the developed hydrogel sponges. Dissolution studies revealed little domperidone release in an acidic environment. However, hydrogel sponges exhibited release up to 10 h in phosphate buffer.The sponge's non-toxic or biocompatible character was confirmed through toxicological studies. Thus, the finding indicates that quince/pectin cross-linked hydrogel sponges are durable enough to deliver the domperidone to the gut for a longer time.

Synthesis, design, in silico, in vitro and in vivo (streptozotocin-induced diabetes in mice) biological evaluation of novels N-arylacetamide derivatives

The organic compounds 2-chloro-N-(aryl)acetamide (Ps13–Ps18) and 2-azido-N-(aryl)acetamide (148–153) were synthesized and analyzed using 1 H, 13C NMR. The acute oral toxicity study was carried out according to OECD guidelines, which approve that the compounds (Ps18 and 153) were nontoxic. In addition, the compounds were evaluated for its antidiabetic and antihyperglycemic properties (in vitro and in vivo) and for antioxidant activity by utilizing several tests as 1,1-diphenyl2-picrylhydrazyl DPPH, (2,2’-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid) ABTS, reducing power test FRAP and hydrogen peroxide activity H2O2 . The molecular docking studies were performed to investigate the antidiabetic activity of Ps18 and 153 and compared with the experimental results. These compounds are a potent antidiabetic from both the experimental and molecular docking results. Finally, the physicochemical, pharmacokinetic and toxicological properties of Ps18 and 153 have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction. Communicated by Ramaswamy H. Sarma

Acute and Sub-Acute Oral Toxicity Studies of Hydroalcoholic Extract of Terminalia arjuna (Roxb.) Bark in Rodents

Acute and Sub-Acute Oral Toxicity Studies of Hydroalcoholic Extract of Terminalia arjuna (Roxb.) Bark in Rodents

Acute oral toxicity study of Acideem Plus Tablet: An Ayurvedic polyherbal formulation

Objective: This study aimed to evaluate the acute oral toxicity of Acideem Plus Tablet in female wistar rats. Materials and Methods: 12 rats were divided into four groups of three at random. Group 1 acted as the control and merely received distilled water. Acideem Plus Tablet, doses of 2000 mg/kg body weight, was given to groups 2 and 3, while group 4 received doses of 5000 mg/kg body weight. For 14 days, the rats were monitored for any indications of toxicity. At the end of the study period, all rats underwent necropsy, and gross pathology was documented. Results: According to the results, neither the rats in the treatment group nor the control group displayed any clinical indications of toxicity or mortality over the course of the 14-day observation period. The LD50 value was found to be greater than 5000 mg/kg body weight. Conclusions: The acute oral toxicity study of Acideem Plus Tablet in wistar rats concluded no adverse effect at doses up to 5000 mg/kg body weight. These results demonstrated the safety of the Acideem Plus Tablet's oral administration.

Toxicity and antidotal treatment by synthesized and optimized ferric(III) hexacyanoferrate(II) for thallium

Abstract Background The active pharmaceutical ingredient (API) of USFDA-approved Radiogardase®-Cs capsule is ferric(III) hexacyanoferrate(II) which is commonly known as Prussian blue insoluble (PB). It enhances the elimination of radioactive or non-radioactive caesium/thallium (Cs(I)/Tl(I)) from the body. The API of Radiogardase®-Cs capsules is not available commercially; therefore, in-house API was synthesized and evaluated. The present study includes toxicity evaluation and in vivo Tl(I) removal efficacy of in-house synthesized and optimized PB prepared by direct (PB-1) and indirect (PB-2) synthesis methods. PB-1 and PB-2 were evaluated for acute and sub-acute oral toxicity in accordance with OECD guidelines in rats. Results No significant changes were observed in treatment groups as compared to the control group of acute and sub-acute oral toxicity studies. The food intake, water consumption, body weight, clinical signs, organ weight and histopathological, biochemical and haematological parameters were monitored. The study found no evidence of mortality. The results indicated that the synthesized PB-1 and PB-2 were safe. As a result, the study further examined PB-1 and PB-2 for removal of Tl(I) in rats. A significant increase in Tl(I) removal was observed when PB-1 and PB-2 were administered orally to rats in comparison to no treatment group. The Tl(I) removal efficacy of PB-1 and PB-2 was comparable to Radiogardase®-Cs treated group. Results showed reduction in the body burden of Tl(I) as well as a higher level of elimination of Tl(I) in faeces and urine. Conclusions The study provides substantial support regarding Tl(I) removal efficacy and safety of in-house synthesized PB-1 and PB-2 which can be used for formulation development.

Phytochemical Analysis, Antioxidant Activities In Vitro and In Vivo, and Theoretical Calculation of Different Extracts of Euphorbia fischeriana

Euphorbia fischeriana has a long-standing history of use in traditional medicine for the treatment of tuberculosis diseases. However, the plant’s therapeutic potential extends beyond this specific ailment. The present study aimed to investigate the antioxidant properties of Euphorbia fischeriana and lay the groundwork for further research on its potential therapeutic applications. Phytochemical tests were performed on the plant, and 11 types of phytochemicals were identified. Ultraviolet–visible spectrophotometry was used to evaluate the active components and antioxidant properties of eight different solvent extracts, ultimately selecting acetone extract for further research. UHPLC-ESI-Q-TOF-MS identified 43 compounds in the acetone extract, and chemical calculations were used to isolate those with high content and antioxidant activity. Three stability experiments confirmed the extract’s stability, while cell viability and oral acute toxicity studies demonstrated its relatively low toxicity. In rats, the acetone extract showed significant protective effects against D-galactosamine-induced liver damage through histopathological examination and biochemical analysis. These results suggest that Euphorbia fischeriana’s acetone extract has potential in treating diseases related to oxidative imbalances. Therefore, this study highlights the plant’s potential therapeutic applications while providing insight into its antioxidant properties.