Acute Toxicity Test Research Articles

BBPT attenuated 6-OHDA-induced toxicity by modulating oxidative stress, apoptotic, and inflammatory proteins in primary neurons and rat models of Parkinson's Disease

Parkinson’s disease (PD) results from the degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Adenosine A2AR acting through the striato-pallidal pathway has emerged as a non-dopaminergic target in the therapy of PD. In the present work, the anti-parkinsonian potential of (4E)-4-(4-bromobenzylideneamino)-3-phenyl-2,3-dihydro-2-thioxo- thiazole-5-carbonitrile (BBPT) was explored. BBPT exhibited significant antioxidant activity in situ. In the MTT assay, the BBPT treatment showed insignificant toxicity to the primary midbrain neuronal (PMDN) cells. 6-OHDA induced PMDN cells, 3h post-treated with BBPT showed 80-85% survival of the cells and restoration of dopamine and TNF-α levels. The acute and sub-acute toxicity test for BBPT was performed with Sprague Dawley (SD) rats. In toxicity assay, any significant physical, hematological, or biochemical changes in the rats were not observed. To evaluate the effect of BBPT in vivo, a 6-OHDA-induced unilaterally lesioned SD rat model of PD was established. We observed that the BBPT treatment improved the behavioral symptoms in 6-OHDA-induced unilaterally lesioned rats. The proteins of 6-OHDA-induced BBPT-treated rats were isolated from the brain tissue to assess the antioxidant effect (GSH, catalase, SOD, lipid-peroxidation, nitrite), dopamine levels, and the restoration in the apoptosis and inflammation. Our results demonstrated that BBPT increased the anti-oxidant enzyme levels, restored the caspase-3/Bcl-2 levels to arrest apoptosis, and attenuated the TNF-α/IL-6 levels, thus restoring the neuronal damage in unilaterally lesioned 6-OHDA-induced SD rats. Precisely, the findings suggested that BBPT possessed significant anti-parkinsonian activity and has the potential to prevent dopaminergic neurodegeneration.

The Fibrotic Phenotype of Human Precision-Cut Lung Slices Is Maintained after Cryopreservation.

Human precision-cut lung slices (hPCLS) prepared from fibrotic lungs recapitulate the pathophysiological hallmarks of fibrosis. These hallmark features can also be induced by treating non-fibrotic hPCLS with a fibrotic cocktail (FC). As a result, the fibrotic and fibrosis-induced hPCLS are rapidly emerging as preferred models for disease modeling and drug discovery. However, current hPCLS models are limited by tissue viability in culture, as they are usually only viable for one week after harvesting. Here, we demonstrate that the fibrotic hPCLS can be cryopreserved, stored for months, and then thawed on demand without loss of hPCLS viability or protein content for 14 days post-thawing. Cryopreservation also preserves the pro-fibrotic potential of non-fibrotic hPCLS. Specifically, when we treated the thawed non-fibrotic hPCLS with an FC, we observed significant pro-fibrotic cytokine secretion and elevated tissue stiffness. These pro-fibrotic changes were inhibited by the small-molecule tyrosine kinase inhibitor, Nintedanib. Taken together, our work indicates that a feasible solution to prolong the pre-clinical utility of fibrotic and fibrosis-induced hPCLS is cryopreservation. We anticipate that cryopreserved hPCLS will serve as an advantageous predictive model for the evaluation of pro-fibrotic pathways during acute and chronic toxicity testing.

Review Article: Study of The Toxicity of Herbal Plants on Vital Organs of Experimental Animals

Background: Indonesia is a tropical country with many natural resources, including flora and fauna. Herbs are natural plants with therapeutic qualities but can also be harmful. As a result, many studies evaluate the toxicity of herbal plants because conducting clinical trials for herbal medicines requires safe treatment. Purpose: This article aims to learn more about the harmful effects of compounds not found in acute and subchronic toxicity tests. The method of writing the article was found through searches in Google Scholar, Science Direct, Research Gate, Garuda, and Pubmed, which are online publications of scientific journals. Several nationally accredited scientific papers, including Sinta 4 and Sinta 5, were accepted. Fifteen literary journals are all relevant to this topic. The toxicity test results reveal that certain plants are classified as non-toxic, slightly toxic, or highly hazardous.

Xanthophyllomyces dendrorhous Is a Safe Dietary Supplement with Potent Antioxidant Defense Enhancing Activity.

Xanthophyllomyces dendrorhous (X. dendrorhous), previously known as Phaffia rhodozyma, is a red yeast that is widely recognized as a rich source of carotenoids, particularly astaxanthin, which exhibits potent antioxidant activity and other health-promoting functions. However, there is currently a lack of research on the safety of consuming X. dendrorhous. To address this, we conducted an acute toxicity study followed by a 90-day subchronic toxicity trial to evaluate the safety of X. dendrorhous and investigate its in vivo antioxidant activity. In the acute toxicity study, Sprague-Dawley rats were administered a maximum of 12 g/kg body weight of X. dendrorhous powder by gavage and survived without any adverse effects for 14 days. In the subsequent subchronic toxicity test, the rats were randomly divided into five groups, each with free access to their diet adulterated with 0% (control), 2.5% (low), 5% (middle), 10% (high), and 20% (extreme high) X. dendrorhous powder. The rats' behavior, body weight, and food intake were monitored during the 90-day experiment. At the end of the experiment, urine, blood, and organs were collected from the rats for biochemical testing. Additionally, the antioxidant activity in rat sera was evaluated. The results of the acute toxicity test demonstrated that the LD50 of X. dendrorhous was greater than 12 g/kg body weight, indicating that the substance was not toxic. Throughout the 90-day period of subchronic toxicity, the triglyceride levels of male rats fed with 10 and 20% X. dendrorhous increased to 1.54 ± 0.17 and 1.55 ± 0.25 mmol/L (P < 0.05), respectively. This may be attributed to the elevated fat content of the diet in the high-dose and extreme high-dose groups, which was 5.5 and 2.5% higher than that in the control, respectively. Additionally, the white pulp in the spleen exhibited an increase, and the number of white blood cells in the extreme high-dose group increased by 2.41 × 109/L (P < 0.05), which may contribute to enhanced immunity. Finally, the body weight, food intake, blood and urine indexes, and histopathological examination results of the organs of the rats did not demonstrate any regular toxic effects. With the adulteration of X. dendrorhous, the activity of GSH-Px in male rats increased by 16-36.32%. The activity of GSH-Px in female rats of the extreme high-dose group increased by 14.70% (P < 0.05). The free radical scavenging ability of ABTS in male rats in the two high-dose groups exhibited an increase of 6.5 and 11.41% (P < 0.05). In contrast, the MDA content of male rats in the extreme high-dose group demonstrated a reduction of 2.73 nmol/mL (P < 0.05). These findings indicate that X. dendrorhous has no toxic effects, can be taken in high doses, and has a beneficial antioxidant effect that may enhance the body's immunity.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine

Ethnopharmacological relevanceIn traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear.Aim of the study: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. Materials and methodsThe effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. ResultsIn the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90–97% and 80–91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. ConclusionsThe present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

DNA interaction of selected tetrahydropyrimidine and its effects against CCl4-induced hepatotoxicity in vivo: Part II.

Tetrahydropyrimidine (compound A = methyl 4-[4'-(heptyloxy)-3'-methoxyphenyl]-1,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate) was chosen for in vivo studies after exhibiting noteworthy in vitro activity against the K562 and MDA-MB-231 cell lines, with IC50 values of 9.20 ± 0.14 µM and 12.76 ± 1.93 µM, respectively. According to experimental (fluorescence titration, viscosity, and differential scanning calorimetry) results, A interacts with DNA via the minor groove. In vivo, acute oral toxicity studies in Wistar albino rats proved no noticeable symptoms of either toxicity or death during the follow-up period. Genotoxic and antigenotoxic studies at three different concentrations of A (5, 10, and 20 mg/kg of body weight) in Wistar albino rats showed that the dose of 5 mg/kg body weight did not cause DNA damage and had a remarkable DNA protective activity against CCl4-induced DNA damage, with a percentage reduction of 78.7%. It is also important to note that, under the investigated concentrations of A, liver damage is not observed. Considering all experimental outcomes realized under various in vivo investigations (acute oral toxicity, genotoxicity, antigenotoxicity, and biochemical tests), compound A could be a promising candidate for further clinical testing.

Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in Daphnia magna: An Advanced Ecotoxicological Testing Tool.

This study demonstrated the strengths of in vivo molecular staining coupled with automated imaging analysis in Daphnia magna. A multiwell plate protocol was developed to assess mitochondrial membrane potential using the JC-1 dye. The suitability of five common anesthetics was initially tested, and 5% ethanol performed best in terms of anesthetic effects and healthy recovery. The staining conditions were optimized to 30 min staining with 2 μM JC-1 for best J-aggregate formation. The protocol was validated with the model compound carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and used to measure the effect of four environmental contaminants, 2,4-dinitrophenol, triclosan, n-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and ibuprofen, on mitochondrial health. Test organisms were imaged using an automated confocal microscope, and fluorescence intensities were automatically quantified. The effect concentrations for CCCP were lower by a factor of 30 compared with the traditional OECD 202 acute toxicity test. Mitochondrial effects were also detected at lower concentrations for all tested environmental contaminants compared to the OCED 202 test. For 2,4-dinitrophenol, mitochondria effects were detectable after 2 h exposure to environmentally relevant concentrations and predicted organism death was observed after 24 h. The high sensitivity and time efficiency of this novel automated imaging method make it a valuable tool for advancing ecotoxicological testing.

Acute and Sub-acute Oral Toxicity Studies of an Aqueous Extract of Ocimum gratissimum (Lamiaceae) in the Mouse Mus Musculus

Ocimum gratissimum is a medicinal plant that is widely used in the world, and has multiple uses in traditional medicine, including the treatment of epilepsy in children. The objective of this study was to evaluate the acute and subacute toxicity of decoction of Ocimum gratissimum leaves in Mus musculus mice. For the acute toxicity test, a single dose of 50, 300 and 2000 mg/kg of extract was administered orally to randomly selected to mice; then they were observed for 14 days. In the subacute study, the extract was administered orally daily to mice of both sexes at doses of 250, 500 and 1000 mg/kg body weight during the 28 days of the experiment. finally, Body weight was measured weekly, haematological, biochemical and histological analysis were performed. The aqueous extract of Ocimum gratissimum did not cause any mortality or significant changes in relative animal and organ weights during the acute and subacute tests at all doses. Few significant changes in food and water intake were observed at the dose of 1000 mg/kg. The highest dose of aqueous extract (2000 mg/kg) administered orally in the acute toxicity did not induce mortality. There were no significant changes in haematological parameters in the different batches treated. Therefore, the oral aqueous extract of Ocimum gratissimum did not produce any adverse side effects compared to the control group (distiller water) in the acute and subacute study. We can therefore conclude that Ocimum gratissimum can be considered safe in oral administration at the dose tested since it did not cause lethality or undesirable effects in general behaviour in white mice.

TOXICITY AND HAEMATOLOGICAL CHANGES OF Datura innoxia STEM ON Clarias gariepinus JUVENILES

The acute toxicity and haematological changes of Datura innoxia stem on Clarias gariepinus juveniles was investigated in a static bioassay to determine the Median Lethal concentrations (LC50) at 96 hrs of exposure. Six graded concentrations of 0, 320, 330,340, 350 and 360mg/l of the aqueous extract were applied to C. gariepinus juveniles in plastic bowls. The result obtained revealed the 96hrs LC50 values to be 86.67mg/l with an 87% confidence interval between the lower and higher limits of 320 and 360mg/l. Fish exposed to acute toxicity test exhibited several abnormal behaviours, including air gulping/gasping, erratic swimming, discolouration haemorrhage, loss of reflex and molting were observed at the bottom of the bowl just before death The oxygen consumption by juveniles decreased with increased concentrations of Datura innoxia stem extract. The packed cell volume (31.34-34.78%), the red blood cell counts (1.75-2.01), haemoglobin (9.03-11.12g/dl) and mean corpuscular haemoglobin concentration were significantly depleted while, white blood cell counts (6.05-7.21) significantly decreases as the concentrations of Datura innoxia stem extract increases. The implication of these findings revealed that the stem of D. innoxia stem have negative effects on the test fish. The toxic effect of Datura innoxia stem on Clarias gariepinus juveniles were both time (12hrs) and dose dependent (340mg/l). It was concluded that Datura innoxia stem are harmful to Clarias gariepinus juveniles with significant haematological alterations.

Acute Toxicity Test of Zebrafish, Antifungal and Antibiofilm Activity of Etlingera rubroloba A.D Poulsen against Candida albicans

Acute Toxicity Test of Zebrafish, Antifungal and Antibiofilm Activity of Etlingera rubroloba A.D Poulsen against Candida albicans

The physiological effects of acute and sub-lethal exposure to phenol on antioxidant enzyme activity in the freshwater sludge worm Tubifex tubifex

The current study investigates the severe effects of commonly employed chemicals, such as phenol, on the freshwater bottom-dwelling annelids of Tubifex tubifex. In an acute toxicity test, phenol's 96-hour LC50 value against Tubifex tubifex was identified to be 221.552 mg/L. Using the GUTS simulation, which places the GUTS-SD model on top of the GUTS-IT model, it was possible to confirm that the test organism would survive an acute exposure to phenol overall. After 14 days of treatment with 10 % and 20 % of the phenol's 96-hour LC50 values, long-term bioassays revealed changes in protein levels and in oxidative stress enzyme levels. Total protein concentration dropped during the bioassay, but levels of antioxidant enzymes (CAT, GST, SOD, and MDA) increased. The Pearson correlation matrix and the Integrated Biomarker Response (IBR) index were used for examining the relationship between biomarkers, toxicants, and phenol-induced stress. The results show that exposure to phenol is detrimental to the survival and general health of Tubifex tubifex.

Cinnamon essential oil incorporated chitosan submicron emulsion as a sustainable alternative for extension of mango shelf life

In the present study, cinnamon bark essential oil (CEO)-incorporated chitosan-based submicron emulsion coatings (CEO-CSSEs) were successfully prepared by an ionic gelation method using sodium tripolyphosphate (STPP) as a crosslinking agent and Tween 20 as a surfactant. A chitosan:CEO mass ratio ≤1:0.5 was found to have a unimodal and narrow size distribution. The FTIR absorption bands confirmed the successful encapsulation of CEO into the chitosan particles, which exhibited a spherical shape and aggregated regions with cracks. Acute oral toxicity tests revealed that the cinnamon bark essential-loaded chitosan submicron emulsion was nontoxic and could be used for coating mango fruits. Postharvest submicron emulsion coatings on mangos significantly delay physio-chemical changes linked to ripening. However, mangos coated with CEO-CSSEs at 1:0.75 and 1:1 ratios remained unripen, while those coated with CEO-CSSEs at 1:0.5 ratio ripened slowly, implying a negative impact of CEO at higher concentrations on mango quality and shelf quality. Therefore, it is concluded that CEO-CSSEs at 1:0.5 successfully slowed different physio-chemical parameters linked to the deterioration of mango quality; thus, treatments can be suggested to extend the shelf life to 18 days during ambient storage at 25 ± 2 °C and 65% RH.

Synthesis, performance evaluation, and plasticization dynamics of biobased vanillic acid plasticizer for poly(vinyl chloride)

Phthalate-based plasticizers are widely used to improve the flexibility and ductility of engineering plastics. However, their hazardous toxicity and unsustainability have prompted the plastics industry to develop safe and efficient green plasticizers. Therefore, it is imperative to develop safe biobased plasticizers from renewable resources. The ether group had been introduced into renewable vanillic acid to synthesize vanillic acid ester derivatives (VAE) using a clean method, and characterized using various spectral methods. The application performances were compared for VAE and three commercial plasticizers for poly(vinyl chloride) (PVC) plasticization. Dynamic mechanical analysis (DMA) indicated that the presence of VAE could reduce the glass transition temperature of PVC by over 50 %, which is 32 % lower than induced by the dioctyl phthalate. The presence of carbonyl and ether groups in VAE increases the elongation at break of PVC by more than 12 times, and the elongation at break (419.8 %) is 10 % higher than that of acetyl tributyl citrate plasticized PVC. Thermogravimetric analysis and aging experiments indicated that PVC blend plasticized by VAE exhibited superior thermal stability compared to acetyl tributyl citrate. The interaction between PVC and the carbonyl and ether groups in VAE has been demonstrated through multifaceted analysis utilizing density functional theory calculations. The binding energy between fragments was −17.8 kcal/mol, and the interaction was visualized by IGMH. Under this interaction, VAE exhibited extremely low migration in PVC blends. Acute oral toxicity tests were used to demonstrate that VAE is harmless to rats even at high doses. Overall, VAE, as a sustainable, low-risk, and efficient PVC plasticizer, outperforms typical commercial plasticizers and is a promising alternative to phthalates.

Chemical characterization of the essential oil from the leaves of Eugenia flavescens DC. (Myrtaceae) and its potential in the treatment of pain, inflammation, and ethanol- and ethanol/HCL-induced gastric ulcers in mice.

Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.

Phytochemical Screening and Pharmacological Activities of Gentiana ornata from Lauribinayak, Rasuwa, Nepal

Gentiana ornata (Wall. ex G. Don) Griseb, also called decorated gentian or showy gentian, has been used as a decoction plant in temperate regions of Nepal. This work aims to evaluate the phytochemical properties, antioxidant values, and pharmacological properties of this plant collected from Lauribinayak, Gosainkunda Rural Municipality, Rasuwa, Nepal. The extract of whole plant was prepared by cold extraction process at 100% ethanol. Then, the qualitative preliminary phytochemical test of plant extract was performed to know its chemical constituents. The total phenolic content using Folin-Ciocalteu method, total flavonoid content using aluminium chloride colorimetric assay and antioxidant potential of the plant extract were also determined by using diphenylpicrylhydrazyl (DPPH) reagent. The pharmacological activities like oral acute toxicity test, antidiarrheal test and anti-ulcer test were also carried out in laboratory animals. The qualitative phytochemical screening showed the presence of flavonoids, steroids, glycosides, anthocyanin, alkaloids, terpenoids, and phenolic constituents. The total phenolic content, total flavonoid content and antioxidant assay value of this plant extract were 242.64±0.280 mg GAE/g, 39.23±0.005 mg QE/g and 42±0.072 µg/mL respectively. The extract showed no morbidity, mortality, toxicity signs, or symptoms in the oral acute toxicity test. Though it could not show considerable antidiarrheal effect by reducing gastrointestinal motility when compared to the standard drug, loperamide, it showed significant anti-ulcer effects by reducing gastric lesions when compared to the standard drug, sucralfate, which may be due to its mucosal protecting nature. Therefore, isolation and purification of phytochemicals responsible for the pharmacological activity of this plant have been recommended.

Safety evaluation of aqueous extract from Valeriana officinalis L. roots: Genotoxicity, acute, subchronic and teratology toxicity

Ethnopharmacological relevanceValeriana officinalis L., commonly known as “valerian”, is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. Aim of the studyThis study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). Materials and methodsThe genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague–Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague–Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. ResultsAEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. ConclusionIn vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

Phytochemical analysis, toxicity assessment, and wound healing properties of Emilia sonchifolia L. leaf extract in rats

Emilia sonchifolia is used in ethnomedicine to treat various diseases such as diarrhoea, diabetes, inflammation, cuts and wounds. This research focused on analyzing the phytochemical composition, toxicity levels, and wound healing effects of the leaf extract of Emilia sonchifolia (LEES). The phytochemical evaluation of LEES was conducted using gas chromatography-mass spectrometry (GC–MS). During the acute toxicity test, rats were orally given a single dose of aqueous LEES up to 5 g/kg. In the subacute toxicity assessment, the rats were separated into four groups. Group 1 (normal control), and groups 2, 3, and 4 were given oral doses of 200, 400, and 600 mg/kg of ALEES. The GC–MS LEES analysis identified fifty five (55) chemical constituents, with eight bioactive compounds including limonene, D-carvone, hexadecane, tetradecane, 1-docosene, 9-octadecenoic acid (Z)-, 2,3-dihydroxypropyl ester, 2-piperidinone, N-[4-bromo-n-butyl]- and oleic acid. No signs of toxicity or death were observed following a single dose administration of 5 g/kg. Oral administration of ALEES led to significant reductions (p < 0.05) in total cholesterol, low-density lipoprotein cholesterol, and triacylglycerol levels compared to the control group. Rats administered with ALEES exhibited dose-dependent elevations (p < 0.05) in the levels of glutathione peroxidase and superoxide dismutase. No significant changes (p > 0.05) were observed in the haematological indices, serum liver and renal biomarkers between the test and control groups. In wound healing studies, ALEES demonstrated higher wound contraction percentage and tensile strength in comparison to the control group. This study ultimately revealed that ALEES is non-toxic, yet contains bioactive compounds with pharmacological properties. These activities are associated with its ability to lower lipid levels, act as an antioxidant, and promote wound healing.

Delayed treatment with hydro-ethanolic extract of Khaya grandifoliola protects mice from acetaminophen-hepatotoxicity through inhibition of c-Jun N-terminal kinase phosphorylation and mitochondrial dysfunction

The use of N-acetylcysteine against acetaminophen(APAP)-induced hepatotoxicity, a leading cause of liver injury, has several drawbacks, including short therapeutic windows. Khaya grandifoliola (Meliaceae) has been traditionally used to manage liver-related diseases, and many reports have confirmed its hepatoprotective properties. However, its therapeutic potential as an antidote against APAP-induced hepatotoxicity has yet to be proven in a clinically relevant model. This study aimed to verify the efficacy of delayed treatment with the hydroethanolic extract of K. grandifoliola (KgE) in suppressing the early injury phase of APAP pathophysiology. KgE was analyzed using HPLC/UV. Acute oral toxicity tests were conducted in mice to determine the therapeutic dose of KgE. Mice were treated with 300 ​mg/kg APAP; 1h and 12h later, they were treated with either predetermined doses of KgE or 20 ​mg/kg c-Jun N-Terminal Kinase (JNK) inhibitor SP600125, which served as a reference antidote. At 6h and 24h after APAP treatment, the parameters of liver damage and mitochondrial dysfunction, phosphorylation of JNK, and mitochondrial translocation were assessed. KgE at a dose of 5000 ​mg/kg was safe for mice. Accordingly, 100, 200, and 400 ​mg/kg were selected as curative treatments. Delayed administration of KgE reversed the histopathological changes in the liver, inhibited serum levels of alanine aminotransferase, reduced the liver content of nitric oxide and malondialdehyde, and restored hepatic glutathione pools and superoxide dismutase and catalase activities in APAP-intoxicated mice. Moreover, KgE prevented APAP-induced JNK phosphorylation and p-JNK mitochondrial translocation and rescued the activities of mitochondrial enzyme complexes II and V. HPLC/UV analysis revealed the presence of gallic acid, Quercetin and Silibinin, with retention times of 3.77, 11.63 and 11.95 ​min as the major active ingredients present in KgE. Our findings demonstrate that post-treatment with KgE protects the mouse liver from APAP-hepatotoxicity through the inhibition of JNK activation and mitochondrial dysfunction.

Acute and chronic effects of the antifouling booster biocide Irgarol 1051 on the water flea Moina macrocopa revealed by multi-biomarker determination

Irgarol 1051 is an herbicide extensively utilized in antifouling paint due to its ability to inhibit photosynthesis. Irgarol and its photodegradation products are highly persistent in waters and sediments, although they are present in low concentrations. However, our understanding of the harmful effects of Irgarol on non-target organisms remains limited. In this study, we assessed the effects of acute (24 h) and chronic (14 days across three generations) exposure to different concentrations (including the 1/10 NOEC, NOEC, and 1/10 LC50 calculated from the 24-h acute toxicity test) of Irgarol using the water flea Moina macrocopa. Acute exposure to 1/10 LC50 significantly decreased survival, feeding rate, thoracic limb activity, heart rate, and acetylcholinesterase activity. Elevated levels of intracellular reactive oxygen species and malondialdehyde, along with a significant increase in catalase and superoxide dismutase activity, suggested the induction of oxidative stress in response to 1/10 LC50. An initial boost in glutathione level and the enzymatic activities of glutathione peroxidase and glutathione reductase, followed by a plunge, implies some compromise in the antioxidant defense system. Upon chronic exposure to the NOEC value, both generations F1 and F2 displayed a significant decrease in survival rate, body length, number of neonates per brood, and delayed sexual maturation, suggesting maternal transfer of potential damage through generations. Taken together, Irgarol induced acute toxicity through physiological and cholinergic damage, accompanied by the induction of oxidative stress, in the water flea. Even its sub-lethal concentrations can induce detrimental effects across generations when consistently exposed.

Study on the acute and subchronic oral toxicity of Calculus Bovis Sativus in rats

This study aims to assess the acute and subchronic toxicity of Calculus Bovis Sativus (CBS), which is an ideal substitute for natural Calculus Bovis. After conducting a test of acute toxicity with KM mice of both sexes, it was determined that oral CBS had a lethal dosage (LD50) of greater than 9.26 g/kg BW. For ninety days, Wistar rats were fed on CBS orally at dosages of 0, 167, 501, and 1503 mg/kg BW/day, respectively, as part of the subchronic investigation. A comparison of the controls with the 1503 mg/kg and 501 mg/kg dosage groups revealed significant differences in the hematological and serum biochemical parameters, such as RBC, HGB, MONO%, PLT, LYMPH% and GLU, TP, ALB, and Ca2+, were observed. However, values of the above parameters fell within our laboratory’s normal range. In terms of body weight, food intake, urinalysis, clinical chemistry, and pathology, no other adverse effects were observed. After 90 days of exposure, the no observed adverse effect level (NOAEL) of CBS in rats was determined to be 1503 mg/kg BW/day.