Poisoning Research Articles

A Comparison of European Union and Turkish Reports on the Statistics of Experimental Animal Use in Toxicity Testing.

The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK data after Brexit for 2020 were included too). The total number of listed vertebrates used for regulatory toxicity testing in the full 6-year reporting period in Turkey was 3.6% of that reported for the EU+. However, these numbers showed an increasing trend over the reporting period in Turkey, while the trend decreased in the EU+. In the top three most-used species for regulatory toxicology purposes in Turkey, 41% were fish (68,758 animals), followed by rats (29%; 49,975 animals), and then mice (20%; 33,292 animals). Turkey used low numbers of cats and dogs, while the corresponding number for the EU+ was more than 70-fold higher. Non-human primates were not used at all in Turkey, whereas about 34,000 were used in EU+ laboratories. The majority of toxicity tests (57%) performed in Turkey were categorised as 'Other' toxicity tests, and 27% were acute and sub-acute toxicity tests. Successful replacement alternatives (e.g. in vitro and in silico approaches) are already used in a wide range of research areas. However, although this new research and testing paradigm is underpinned by scientific evidence, the legislation and pace of acceptance of these new techniques in Turkey is considerably lagging behind other countries.

Biocompatibility analysis of titanium bone wedges coated by antibacterial ceramic-polymer layer

This paper presents the surface treatment results of titanium, veterinary bone wedges. The functional coating is composed of a porous oxide layer (formed by a plasma electrolytic oxidation process) and a polymer poly(sebacic anhydride) (PSBA) layer loaded with amoxicillin (formed by dip coatings). The coatings were porous and composed of Ca (4.16%-6.54%) and P (7.64%-9.89% determined by scanning electron microscopy with EDX) in the upper part of the implant. The titanium bone wedges were hydrophilic (54° water contact angle) and rough (surface area (Sa):1.16 μm) The surface tension determined using diiodomethane was 68.6 ± 2.0° for the anodized implant and was similar for hybrid coatings: 60.7 ± 2.2°. 12.87 ± 0.91 µg/mL of amoxicillin was released from the implants during the first 30 min after immersion in the phosphate-buffered saline (PBS) solution. This concentration was enough to inhibit the Staphylococcus aureus ATCC 25923, and Staphylococcus epidermidis ATCC12228 growth. The obtained inhibition zones were between 27.3 ± 2.1 mm–30.7 ± 0.6 mm when implant extract after 1 h or 4 h immersion in PBS was collected. Various implant biocompatibility analyses were performed under in vivo conditions, including pyrogen test (3 rabbits), intracutaneous reactivity (3 rabbits, 5 places by side), acute systemic toxicity (20 house mice), and local lymph node assay (LLNA) (20 house mice). The extracts from implants were collected in polar and non-polar solutions, and the tests were conducted according to ISO 10993 standards. The results from the in vivo tests showed, that the implant’s extracts are not toxic (mass body change below 5%), not sensitizing (SI < 1.6), and do not show the pyrogen effect (changes in the temperature 0.15ºC). The biocompatibility tests were performed in a certificated laboratory with a good laboratory practice certificate after all the necessary permissions.

Interstitial brachytherapy for periocular nonmelanoma skin cancers: Impact on organ and function preservation

PurposeTo study the local control, toxicity, organ and functional preservation and cosmetic outcomes after interstitial brachytherapy for periocular nonmelanoma skin cancers. Methods and MaterialsPatients with skin cancers of upper and lower eyelid, medial and lateral canthus and the infra-orbital region treated with high dose rate (HDR) interstitial brachytherapy (ISBT) using 192-Iridium (192Ir) between December 2010 and July 2022 were included and data collected from a prospectively maintained database. Local control, survival outcomes, acute and late RTOG toxicity, functional and cosmetic outcomes were analysed. ResultsSixteen patients were included. Nine patients had lower eyelid tumors, 5 patients had tumors in canthi and two patients had skin tumor in the infra-orbital region. The median dose for definitive ISBT was 49 Gy in 14 fractions. After a median follow up of 73 months, all patients treated with definitive and adjuvant ISBT were locally controlled. Three of the four patients who received salvage ISBT for post-surgical failure had local recurrences and all were effectively managed with salvage re-surgery. Of the two deaths, none were disease related. Organ and function preservation was achieved in 15 (93.7 %) and 13 (81.2 %), respectively, with one patient being lost to follow up. Excellent, good, fair and poor cosmesis was seen in 6 (40 %) patients, 6 (40 %) patients, 2 (14 %) patients and 1(6 %) patient, respectively. ConclusionHDR-ISBT was safe and effective for skin tumors around the eye and resulted in excellent local control and survival outcomes preserving organ and function in majority of patients with good-excellent cosmesis.

Apodanthera glaziovii (Cucurbitaceae) Shows Strong Anti-Inflammatory Activity in Murine Models of Acute Inflammation.

Background/objectives:Apodanthera glaziovii is an endemic species from the semi-arid Brazilian, which has limited toxicological and pharmacological studies. This species belongs to a well-studied family known for its bioactive compounds used in treating inflammatory. This study aimed to identify secondary metabolites in the stems from A. glaziovii, evaluate toxicity, and investigate the anti-inflammatory potential of the stem hydroalcoholic extract (SHE-Ag). Methods: qualitative and quantitative assays were employed to identify secondary metabolites, along with chromatographic analyses and 1H and 13C NMR. Toxicity was assessed through in vitro hemolytic toxicity, in vivo genotoxicity, and oral acute toxicity tests before the pharmacological assays were conducted. Results: phytochemical screening, HPLC and NMR analyses suggested the presence of saponins of the norcucurbitacin class. The SHE-Ag exhibited no hemolytic activity and no mutagenic potential. However, in vivo toxicity at a dose of 2000 mg/kg revealed hematological and biochemical alterations, while the 500 mg/kg dose was safe. In the anti-inflammatory assays, SHE-Ag at 100 mg/kg reduced paw edema by 55.8%, and leukocyte and neutrophil migration by 62% and 68% in the peritonitis model, respectively; inflammatory cell migration by 70% in the air pouch model, outperforming indomethacin, which showed a 54% reduction. Conclusions: these findings indicate that SHE-Ag is rich in saponins, confirmed through HPLC and 1H and 13C NMR analyses. The SHE-Ag also demonstrated low toxicity. The inflammation models used showed a reduction in inflammation, pro-inflammatory cells, and edema, highlighting the significant anti-inflammatory activity of hydroethanolic extract A. glaziovii stems.

Proteomic Profile of Blood Plasma of Mus Musculus in the Acute Toxicity Test of Single Black Garlic (Allium Sativum)

This study aims to obtain overall information about all proteins formed in body fluids, cells, or tissues at a certain time and to analyze the mechanism of cell responses to various types of stress and drugs. Single black garlic (SBG) has the potential to be a pharmacological agent. However, the safety of using single black garlic is still unknown, so a material toxicity test is needed. This research is a laboratory experimental research with a post-test-only control group design. An oral acute toxicity test was used. Observation time was 14 days and consisted of four treatments, negative control, SBG dose 2000 mg/kgbw (P1), 3000 mg/kgbw (P2), and 5000 mg/kgbw (P3). Post-treatment protein analysis was done using the SDS-PAGE electrophoresis method. Observations of clinical symptoms of SBG at doses of 2000 mg/kgbw, 3000 mg/kgbw, and 5000 mg/kgbw showed no clinical symptoms in mice, both motor activity and pupils were still normal, no convulsions (seizures), lacrimation, paralysis or death were seen in mice. Observations on plasma proteins showed differences in protein between the treatments at the SBG dose of 2000 mg/kgbw with the SBG dose of 3000 mg/kgbw and 5000 mg/kgbw, but the four treatments have the same type of protein in the protein band with a molecular weight of 25 kDa. So, it can be concluded that SBG doses of 2000 mg/kgbw, 3000 mg/kgbw, and 5000 mg/kgbw are not toxic to mice but can stimulate the expression of certain proteins. Keywords: Single Black garlic (SBG), oral acute toxicity test, proteomic analysis, SDS-PAGE

Insight into didecyl dimethyl ammonium bromide toxicity following acute exposure in pullets (Gallus gallusdomesticus).

Didecyl dimethyl ammonium bromide (DDAB) is a quaternary ammonium compound used for the sanitation of drinking water of poultry and water pipelines in farms. There is scarcity of information on the toxicology of DDAB in poultry. This study set out to profile the acute toxicity of DDAB in poultry. Issa brown pullets (n = 34) as experimental birds were orally administered varying doses of DDAB, using a syringe, after 12h fasting, and observed for toxicity over 14 days. Control birds (n = 10) were similarly given normal saline orally. Toxic signs in the experimental birds were depression, anorexia, adipsia, vocalization with foamy salivation, later emaciation and death. The LD50 was calculated as 458.00mg/kg. Birds given 2151mg/kg DDAB died within 24h, while those treated with 516mg/kg succumbed on Day 14. At necropsy, grossly, there were necrosis and sloughing of the oesophagus and intestines, pale and friable liver, congested and necrotic lungs, friable popped out kidneys and emaciated carcasses. Microscopically, desquamation and necrosis of the oesophagus, crop, proventriculus and intestines and disruption of the koilin membrane of the gizzard were observed. The lungs, liver and kidneys were congested with mononuclear cellular infiltration plus loss of architecture in the lungs and liver. In conclusion, at high doses, DDAB caused significant toxicity in chickens and these findings provide new information which could serve as a guide in the diagnosis of quaternary ammonium toxicity in chicken. The results could be extrapolated to other quaternary ammonium toxicities in related avian species.

Early developmental anomalies in zebrafish (Danio rerio) embryos induced by the Clematis florida Thunb.

Ethnopharmacological relevanceThe C.florida. is one of the common medicines used by She population in China, with therapeutic effects of promoting blood circulation and anti-inflammatory. According to the acute toxicity grading standard of chemical substances, this herb is a low-toxicity herb. At present, the safety of C.florida., especially its impact on early embryonic development, is still unclear. Aim of the studyThis study investigated the toxic effects of C. florida. on early embryonic development using a zebrafish embryo model. Materials and methodsIn this study, we used zebrafish embryos exposed to C.florida. at early stage to assess the early developmental toxicity by analyzing the developmental toxicity phenotype, oxidative stress, cell apoptosis, total enzyme activity, behavioral trajectory, and gene expression levels. ResultsEmbryos of the zebrafish exposed to different concentrations of C.florida. exhibited multiple organs and systems developmental disorders, including the heart, vessels, brain, bone, liver, and so on. Especially, with the increase of drug concentration, it is observed that the developmental malformations of the cardiovascular structure and function in larvae are becoming increasingly severe. In addition, results show that the abnormalities in embryonic development may be attributed to oxidative stress induced by apoptosis and activation of immune system resulting from an imbalance in the hematopoietic system. ConclusionsThis study provides a comprehensive and detailed summary of the toxic effects of C.florida. on embryonic development, which contributes to a deeper understanding of the potential adverse developmental consequences, and also prompt people to pay considerable attention to its treatment in medicinal practice.

Subchronic Toxicity of Ethanol Extract of Mangosteen Rind (Garcinia Mangostana L.) on Kidney Function in Wistar Rats

Mangosteen (Garcinia mangostana L.) is a fruit that possesses antioxidant, antibacterial, antihistamine, anti-inflammatory, and antidiabetic properties. Before this, an acute toxicity test was conducted on the ethanol extract of mangosteen rind. However, further testing is required, specifically the subchronic toxicity test, to identify any hazardous effects that may not have been found in the previous study. The objective of this study is to evaluate the amount of toxicity based on the mortality rate, alterations in the relative weight of the kidneys, and changes in renal function as shown by levels of urea and creatinine. This study is an experimental investigation that employs the Post-test Only Control Group Design methodology, with a sample of 40 rats. The rats were categorized into two groups: the control group and the treatment group. The treatment group was divided into three subgroups, each receiving a dosage of 250 mg/kg body weight. The doses were 500 milligrams per kilogram and 1000 milligrams per kilogram of body weight, respectively. The control group received simply water and feed. The duration of the treatment was 28 days. Observations were conducted over 28 days, which involved monitoring animal mortality. On the 29th day, a surgical procedure was carried out to assess the comparative weight of the kidneys and collect blood samples for analyzing the levels of urea and creatinine. The findings demonstrated no mortality in the test subjects, although there was an elevation in the relative mass of the kidneys and an increase in urea concentrations. The increase in urea levels was observed in female rats using the Kruskal–Wallis test (P = 0.019). The study was further conducted using the post-hoc Mann–Whitney test. Control female rats exhibited notable disparities when administered dosages of 250 mg/kgBW and 500 mg/kgBW. The repeated administration of an ethanolic extract derived from the peel of the mangosteen fruit had a detrimental impact on the functioning of the kidneys, as evidenced by a rise in urea concentrations. Keywords: mangosteen, toxicity test, subchronic, kidney

Sharing Mono-Institutional Experience of Treating Pancreatic Cancer with Stereotactic Body Radiation Therapy (SBRT).

Stereotactic body radiotherapy (SBRT) is an evolving treatment for the local management of pancreatic cancer (PC). The main purpose of this study is to report our initial experience in terms of local control (LC) and toxicity for PC patients treated with SBRT. We conducted a retrospective review of patients treated with SBRT using abdominal compression (AC) or an end-expiratory breath-holding (EEBH) technique. The median prescribed dose was 35 Gy, delivered in five fractions. Toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and survival was estimated using the Kaplan-Meier method. From 2017 to 2023, 17 PC patients were offered SBRT. Their median age was 69 years. The median follow-up from the date of diagnosis was 22.37 months. The overall survival (OS) was 94% at 1 year and 60.9% at 2 years. The progression-free survival (PFS) was 63.1% at 6 months and 56.1% at 9 months. The median OS was 26.3 months, and the median PFS was 20.6 months. The 6-month and 1-year LC rates were 71% and 50.8%, respectively. We are successful in implementing the SBRT program at our centre. SBRT appears to be a promising treatment option for achieving LC with limited acute toxicities.

Evaluating the Root Extract of Reynoutria ciliinervis (Nakai) Moldenke: An Analysis of Active Constituents, Antioxidant Potential, and Investigation of Hepatoprotective Effects in Rats

Reynoutria ciliinervis (Nakai) Moldenke (R. ciliinervis) root, a traditional Chinese medicine, was found to exhibit remarkable pharmacological properties through a series of comprehensive investigations. Our study commenced with a qualitative phytochemical analysis that identified 12 bioactive compounds within the plant. Subsequently, utilizing ultraviolet-visible spectrophotometry, the methanol extract emerged as the optimal solvent extract, which was abundant in diverse classes of compounds such as carbohydrates, phenolics, steroids, alkaloids, phenolic acids, and tannins. In vitro antioxidant assays underscored the exceptional free radical scavenging, metal ion chelation, hydrogen peroxide scavenging, singlet oxygen quenching, and β-carotene bleaching capabilities of the methanol extract, significantly outperforming other solvent extracts. Further ultra high-performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry analysis revealed the presence of 45 compounds, predominantly anthraquinones and phenolics, in the methanol extract. The extract demonstrated robust stability under various conditions, including high temperatures, varying pH levels, and simulated gastrointestinal digestion as well as efficacy in inhibiting the oxidation in edible oils. Acute toxicity tests in mice confirmed the safety of the methanol extract and provided a valuable dosage reference for future studies. Importantly, high-dose methanol extract exhibited a significant pre-protective effect against D-galactosamine-induced liver injury in rats, as evidenced by reduced alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, malondialdehyde levels, and elevated catalase and albumin levels. These findings suggest a potential role for the methanol extract of R. ciliinervis root in treating oxidative stress-related disorders, highlighting the plant’s immense medicinal potential. Our research offers a thorough evaluation of the bioactive components, antioxidant properties, stability, and liver-protecting effects of the methanol extract, setting the stage for deeper investigation and potential clinical applications.

Acute toxicity of salicylic acid and its derivatives on the diatom Phaeodactylum tricornutum: Physico-Biochemical and transcriptomic insights

Salicylate pollutants (SAs) poses a serious threat to marine ecosystems as emerging contaminants. However, the toxic effects of SAs on marine phytoplankton, as well as the potential mechanisms and their ecological risks linked with them, are remain largely unknown. In this study, we aimed to evaluate the toxic effects of salicylic acid (SA) and its 5-substituted derivatives (5-sSA) on the marine diatom Phaeodactylum tricornutum, as well as the potential molecular mechanism involved in the toxicity. Physiological assays conducted on P. tricornutum revealed significant changes in photosynthetic pigments, chlorophyll fluorescence parameters, and antioxidant enzyme activities. The results showed that exposure of P. tricornutum to SAs caused a significant decline in chlorophyll contents and damage to the photosystem II (PSII) core resulting in the decline of photosynthesis. Although the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced, oxidative damage occurred. Transcriptome analysis showed that a large number of differentially expresses genes (DEGs) were significantly enriched in metabolic pathways such as porphyrin metabolism, terpenoid backbone biosynthesis, and carbon fixation in photosynthetic organisms after SA and 5-BrSA treatments. In addition, key genes in transcriptomic metabolic pathways were further analyzed and validated using weighted correlation network analysis (WGCNA) and real-time fluorescence quantitative PCR (qPCR). Considering the above results, SAs mainly inhibit the processes of photosynthesis by repressing the expression of genes involved in secondary metabolite synthesis and photosynthetic carbon sequestration pathways, thus exerting toxic effects on algal cells. The results of the study will provide key data for understanding the ecological risk and toxicity mechanisms of SA pollutants.

Cardiovascular effects and clinical outcomes in acute opioid toxicity: A case-control study from Port Said and Damietta Governorates Egypt

Substance abuse, particularly opioid intoxication, presents a significant public health challenge, leading to severe cardiovascular complications. This case-control study assessed the cardiac profile and clinical outcomes of 51 patients with confirmed acute opioid toxicity, compared to 51 control participants, in general hospitals across Port Said and Damietta governorates, Egypt. The study revealed that opioid-intoxicated patients exhibited significant cardiovascular abnormalities, including hypotension (39.2 %) and electrocardiogram (ECG) changes (72.5 %), with sinus bradycardia (51 %) being the most common. Additionally, echocardiographic abnormalities were found in 40 % of cases, with abnormal regional wall motion and valvular defects observed in several patients. Elevated levels of cardiac enzymes, such as Troponin-I and CK-MB, were significantly correlated with increased ICU stay length and higher mortality rates. The most common morbidities included coma (64.7 %) and shock (39.2 %). The study underscores the critical need for early cardiac assessment in opioid-intoxicated patients to predict clinical outcomes and guide therapeutic interventions.

Determination of acute sertraline intoxication by high-performance thin-layer chromatography

Determination of acute sertraline intoxication by high-performance thin-layer chromatography

Risk assessment of Arsenic in surface water of China water systems based on a time-dependent species sensitivity distribution (SSD) method

Arsenic (As) is a naturally occurring metalloid element widespread in the environment. Assessing the ecological risk of As in surface water, especially the acute risk caused by emergent pollution incidents, is of great significance. However, acute toxicity data including median lethal concentration (LC50) and median effective concentration (EC50) of As derived by toxicology experiment may vary according to the exposure time, which is referred as time dependence effect. Time dependence not only affects toxicity data but also influences the characterization of acute risk in the ecosystem. However, previous research on the time dependence effect of As, especially the quantitative influence on the risk assessment is still limited. In this research, acute toxicity data of As(III) and As(V) was collected. Time dependence of toxicology data of inorganic As was studied. Time-dependent species sensitivity distributions of freshwater species were established. The hazardous concentration for 5% of species (HC5) values in different exposure time were further derived. Finally, the dynamic ecological risk of As in major Chinese water basins was evaluated. The results suggested that the toxicity data of inorganic As had a significant linear relationship (p < 0.01) with time. The HC5 values of As (III) and As (V) at an exposure time of four days were reduced by 15.5% and 77.5%, respectively, as compared to the HC5 value of one day. According to the ecological risk characterized by the probability density overlapping area method, the ecological risk of As(III) and As(V) increases with the exposure duration. The Yangtze River had the highest risk, with risk values ranging from 19.9% to 22.6%. According to the results, the time dependence of toxicity data should be fully considered in the formulation of water quality criteria or ecological risk assessment so as to provide better protection for the water ecosystem security.

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.

Acute and Sub-Acute Toxicity Studies of Soursop Starch in Swiss Mice and Wistar Rats

Acute and Sub-Acute Toxicity Studies of Soursop Starch in Swiss Mice and Wistar Rats

Pinonic Acid Derivatives Containing Thiourea Motif: Promising Antifungal Lead Compound Targeting Cellular Barrier of Colletotrichum fructicola.

In order to explore novel antifungal lead compounds from plant essential oil, thirty-two pinonic acid derivatives containing thiourea groups were designed and synthesized using α-pinene as a raw material. One of these pinonic acid derivatives compound 3a exhibited noteworthy in vitro antifungal activity against Colletotrichum fructicola (EC50 = 9.22 mg/L), which was comparable to that of the positive control kresoxim-methyl (EC50 = 9.69 mg/L). Structure-activity relationship (SAR) studies demonstrated that the introduction of thiourea groups, F atoms, and Cl atoms into the structure of pinonic acid derivatives significantly improved their antifungal activity. The in vivo antifungal test revealed that compound 3a could effectively control pear anthracnose. It also proved that compound 3a showed low acute oral toxicity to honeybees (LD50 > 100 μg/bee) and low or no cytotoxicity to LO2 and HEK293 cell lines. The preliminary mechanism of action studies revealed that compound 3a caused mycelium deformity, increased cell membrane permeability, blocked the normal process of phospholipase C on the cell membrane, and reduced mycelium protein content. The results of molecular docking studies demonstrated the stable binding of compound 3a to phospholipase C and chitin synthetase. This study suggested that compound 3a could be used as a promising lead compound for the development of novel antifungal agents targeting the cellular barrier of C. fructicola.

A novel pectin-like polysaccharide from Crocus sativus targets Galectin-3 to inhibit hepatic stellate cells activation and liver fibrosis

Liver fibrosis may lead to cirrhosis and even cancer without effective clinical medicine available. Previous studies demonstrated that galactan-containing pectins or pectin-like polysaccharides might target Galectin-3 (Gal-3) to impede fibrosis. This research aims to discover novel pectin-like galactan to interfere with fibrosis for potential new drug development. Thus, we purify a novel homogeneous Rhamnogalacturonan-I like polysaccharide with galactan input, XHH2, from the Crocus sativus flower. XHH2 (MW: 35.7 kDa) consists of rhamnose, galacturonic acid, galactose, and arabinose in ratios of 6.6: 6.1: 25.2: 12.1. The backbone of XHH2 comprises 1, 3, 6-Gal and 1, 3, 4-GalA, with branches at O-3 of 1, 3, 6-Gal and O-4 of 1, 3, 4-GalA. O-3 branches include 1, 3-Gal, 1, 4-Gal, 1, 6-Gal, T-Gal, and T-Glc, while O-4 branches consist of 1, 2, 4-Rha, 1, 4-GalA, 1, 5-Ara, T-Ara, T-Gal, and T-α-HexA. Surface plasmon resonance measurement shows that XHH2 binds to both Gal-3 and integrin β1 to block Gal-3/integrin β1 interaction. Mechanism studies further suggest that XHH2 inactivates hepatic stellate cells (HSCs) via disturbing the Gal-3/Integrin-β1/FAK pathway to alleviate liver injury and fibrosis in vitro &in vivo. XHH2 shows a favorable drug safety in the acute toxicity test of oral administration of XHH2 in mice. Overall, XHH2 is an active ingredient against liver fibrosis by targeting the interaction between Gal-3 and Integrin-β1.