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Background: 18KHT01 is a novel synergistic composition of Quercus acutissima, Camellia sinensis, Geranium thunbergii, and a small portion of Citrus limon. Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet‐induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. Methods: Broad‐spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC‐DAD) method was developed and validated using six marker compounds. Results: Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no‐observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30‐day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long‐term administration in ICR mice of either sex. UPLC‐DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. Conclusion: The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control. [ABSTRACT FROM AUTHOR]

We aim to investigate perioperative and subacute postoperative complications in patients undergoing LDR or HDR monotherapy for prostate cancer. We hypothesize a low rate of complications, and a favorable toxicity profile in patients treated with HDR compared to LDR. A prospectively collected institutional database was queried for patients treated with HDR or LDR prostate monotherapy between 1998 and 2021. Toxicities were determined per CTCAE. Claims based billing codes were obtained to identify additional events. Events occurring within 4 months of treatment were defined as perioperative or subacute postoperative complications. 759 patients were identified, 446 received LDR with 125I, and 313 received HDR with 192Ir. HDR patients had higher risk features: 75.7% with Gleason score 7+ versus 2.4% of LDR, and 16% with initial PSA 10+ ng/mL versus 2.7% of LDR. Toxicities were mild with the most common being grade 1 GU frequency and nocturia at ∼50%. HDR patients had significantly less grade 2 dysuria (2.6% vs. 9.0%), frequency (4.8% vs. 9.4%), hematuria (1.0% vs. 5.2%), nocturia (3.8% vs. 9.4%), and urinary obstructive symptoms (7.3% vs. 11.2%), all statistically significant. 11 (1.4%) patients had infection requiring antibiotics: 8 (1.8%) from the LDR group and 3 (1%) from the HDR group. Cardiopulmonary events were low at <2% overall, without difference between HDR and LDR. Overall toxicity rates support the safety of prostate brachytherapy. HDR monotherapy is associated with significantly less perioperative and subacute postoperative GU events when compared to LDR monotherapy. Cardiopulmonary events were equally rare in both groups. [ABSTRACT FROM AUTHOR]

Medicinal plants harbor numerous natural bioactive compounds with therapeutic potential, utilized in the synthesis of various drug formulations. While the diverse benefits of herbal formulations have been extensively researched, a toxicity assessment is crucial to establish a wide margin of safety for the therapeutic application of this polyherbal formulation. The recent study aimed to assess the phytochemical profile and potential toxic effects of an aqueous extract derived from a polyherbal formulation containing Petroselinum crispum L., Coriandrum sativum L., and Apium graveolens L. The investigation involved acute and sub-acute toxicity studies conducted in male and female Swiss albino mice, as well as adult rats. High-performance liquid chromatography analysis revealed a rich composition of phytochemical compounds in the extract. In acute toxicity assessments, oral administration of the extract up to 14 g/kg showed no signs of toxicity or fatalities in mice. However, intraperitoneal administration resulted in dose-dependent toxicity, with a calculated LD 50 of 11.8 g/kg. Sub-acute toxicity studies in rats over 28 days showed no significant changes in organ weights, hematological, or biochemical parameters, except for a minor decrease in WBC count. Histopathological examination revealed no morphological disturbances in the liver and kidneys, indicating a wide margin of safety for therapeutic use. [Display omitted] • This is the first report on the toxicity assessment of the Moroccan polyherbal formulation containing Petroselinum crispum L., Coriandrum sativum L., and Apium graveolens l. • The acute and subacute toxicity profiles of the polyherbal formulation aqueous extract in mice and rats. • The lethal dose 50 (LD 50) for the polyherbal formulation via oral administration exceeded 14 g/kg, while it equaled 11.8 g/kg for intraperitoneal administration. • No severe toxic effects on hematological and biochemical parameters, as well as vital organs, were observed in the subacute toxicity test conducted over a period of 28 days. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the acute and subacute toxicity of the of Aphrodisiac Herbal Formulation in albino rats. The acute toxicity was performed where the limit dose of 2000 mg/kg body weight used. Observations were made and recorded for 24 h, and once daily further for a period of 14 days. The rats were weighed and various observations, like mortality, behaviour, injury, or any signs of illness were conducted once daily during the period. For subacute study, four groups of 10 animals (female rats) received 60mg/kg, 120mg/kg and 200mg/kg oral by dissolving in water for 28 days. of freshlyprepared Aphrodisiac Herbal Formulation, respectively, every 24 h orally for 28 days. At the end of each study, haematological analysis and biochemical parameters were evaluated. Histopathological examination of vital organs of the animals were taken for gross findings, compared to controls. There was no significant difference (p > 0.05) observed in the relative organs, body weights, haematological, biochemical parameters, and gross abnormalities, compared to the control. No mortality was recorded. Therefore, analysis of results may lead to the conclusion that the medium-term oral administration of the Aphrodisiac Herbal Formulation for 28 days does not cause toxicity. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this investigation was to assess the subacute oral toxicity of the Pankajakasthuri Orthoherb Tablets, a polyherbal formulation used to manage pain and inflammation due to various pathological reasons, including osteoarthrosis, polyarthritis, rheumatoid arthritis, and other chronic degenerative disorders. Materials and Methods: The subacute toxicity studies of Pankajakasthuri Orthoherb Tablets were conducted using Wistar albino rats of both sexes, according to Organization for Economic Cooperation and Development-approved procedures. In this study, rats were orally administered Pankajakasthuri Orthoherb Tablets daily at doses of 250, 500, and 1000 mg/kg body weight for 28 days. Throughout the study period, general behavior, mortality, and adverse effects were recorded. Body weight, selected hematological and clinical chemistry parameters were determined at the end of the investigation period. Finally, histopathological analysis was performed to determine whether the study drug was inducing any alternations in the vital organs. Results: Daily administration of Pankajakasthuri Orthoherb Tablets for a continuous 28 days did not record any major toxicity indications. Additionally, no significant variation in food and water consumption, body weight, relative organs and hematology and clinical chemistry parameters was recorded in both sexes compared to the control. Histopathological investigation of the vital organs also revealed normal architecture, which suggests no morphological alterations after the administration of Pankajakasthuri Orthoherb Tablets. Conclusion: The outcomes of this investigation confirmed that Pankajakasthuri Orthoherb Tablets did not have the potential to induce toxicity signs in the experimental rats. The No observed Adverse Effect Level (NOAEL) for female and male rats of Pankajakasthuri Orthoherb Tablets under these experimental conditions was 500 mg/kg body weight. Based on the NOAEL, the human equivalent dose of the Pankajakasthuri Orthoherb Tablet was calculated at 5.195 g/day. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future. [ABSTRACT FROM AUTHOR]

Vernonia amygdalina's medicinal properties are well established. Furthermore, the safety of the V. amygdalina leaf aqueous fraction has yet to be proven. This study aims to determine the subacute toxicity of Vernonia amygdalina leaf aqueous fraction (VALAF) on haematological parameters in male BALB/c mice. The sub-acute oral toxicity test consisted of three treatment groups of nine animals each and a control group. The BALB/c mice were given repeated oral doses of VALAF at 250, 500, and 1000 mg/kg BW for 21 days. The observed parameters were red blood cells (RBC), haemoglobin (Hb), white blood cells (WBC), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and hematocrit (HCT). All parameters were measured on the 8th, 15th and 22nd days. This study revealed no mortality or morbidity in the subacute toxicity tests. VALAF dose and the duration of administration did not differ significantly from the control group (p>0.05). This study showed that VALAF was relatively safe for male BALB/c mice. [ABSTRACT FROM AUTHOR]

SCIENTIFIC RELEVANCE. Studies of the inhalation administration of chemicals are associated with challenges in designing experiments. The parameters to be selected include the experimental animal species, the inhalation chamber, and the mode of inhalation (dynamic or static).AIM. This study aimed to analyse the practical application of regulatory requirements to non-clinical studies of the inhalation toxicity of chemicals.DISCUSSION. This review compares international and Russian standards for studying the inhalation toxicity of chemicals, including GOST 32542-2013, GOST 326432020, GOST 32636-2020, GOST 32383-2013, and GOST 2646-2014. The improvement of the legal and regulatory framework correlates with adopting the Good Laboratory Practice and the risk-based approach to categorising test substances into hazard classes. Hazard classes are determined in rodents without dose extrapolation to humans. The authors present the differences between the main guidelines on inhalation exposure in rodent studies of acute, subacute, subchronic, and chronic toxicity. The article describes current approaches to assessing the inhalation toxicity of chemicals, which allow researchers to replace animal studies with in vitro tests.CONCLUSIONS. According to the current regulatory standards, inhalation toxicity is studied in rats/mice, which have anatomical differences from humans. As an alternative to animal studies, researchers are developing and validating in vitro methods, which yet require regulatory review and approval.

Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. Erigeron annuus (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that Erigeron annuus extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used H2O2-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with H2O2 showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. Methods: Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. Results: The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. Conclusion: In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Deltamethrin is one of the most effective pyrethroid compounds, widely employed in veterinary medicine, public health, and farming. Deltamethrin-triggered oxidative stress largely causes serious harm to an organism. Acute toxicity of this compound was extensively investigated, while less information is available on its oral sub-acute effects. This study assessed, in the male Albino rats, the effects of oral gavage of either 0.874 mg/kg (0.01 LD50) or 8.740 mg/kg (0.10 LD50) of deltamethrin for successive 14 days to investigate its effects on biomarkers and to detect the tissue injury in rats following subacute deltamethrin treatment. It was found that levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, kidney, and liver, alkaline phosphatase (ALP), and uric acid in serum, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC)s, eosinophils, and basophils were significantly reduced compared with untreated rats. However, when rats were treated with deltamethrin for successive 14 days, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in serum and the levels of thiobarbituric acid reactive substances (TBARs) in brain, kidney, and liver, red blood cell distribution width (RDW-CV), total protein, monocytes, and basophils and the ratios of neutrophils to lymphocytes, an aggregated marker of systemic inflammation and systemic immune inflammation indexes, significantly increased compared with the control group. Histologic lesions were observed in the liver, kidney, brain, testis, and epidemies in rats exposed to subacute deltamethrin for 14 days, and most tissues of rats treated with 0.10 LD50 of deltamethrin were more affected than those treated with 0.01 LD50. These findings strongly suggest that subacute exposure to deltamethrin caused significant systemic toxicity through oxidative stress resulting in biochemical and histological changes in the studied tissues. These findings highlight the potential harmful effects of deltamethrin and emphasize the importance of understanding the subacute effects of this compound, particularly in the context of veterinary medicine, public health, and farming. [ABSTRACT FROM AUTHOR]

The current study aimed to find out the anti-arthritic activity and safety study of Coronopus didymus aqueous extract (CDAE) as well as its chemical characterization by HPLC–DAD. Safety study including acute and subacute toxicity studies of the plant aqueous extract was also performed. In complete Freund's adjuvant-induced arthritic model (CFA), 0.15 ml CFA was injected in the left hind paw at day 1 in all rats except normal rats. Treatment with CDAE at 200, 400, and 800 mg/kg and methotrexate (1 mg/kg) was administered at day 8 and continued till 28th day using oral gavage. The CDAE considerably (p < 0.05) reduced the paw swelling and arthritic score, and reinstated the body weight and blood parameters. The CDAE considerably modulated superoxide dismutase, catalase, reduced glutathione, and malondialdehyde level in liver homogenate in contrast to disease control. The CDAE at 400 mg/kg considerably reduced IL-6, IL -1β, COX-2, and NF-ĸβ, whereas elevated IL-10, IL-4, and I-kappa β as equated to disease and standard groups. The LD50 of CDAE > 2000 mg/kg. In subacute toxicity study, CDAE at 200–800 mg/kg did not exhibit clinical signs of toxicity, mortality, hematological, biochemical, and histological alteration in the liver heart, kidney, and lungs in contrast to the normal group. It was concluded that the presence of delphinidine-3-glucoside, diosmetin, 3-feruloyl-4,5-dicaffeoyl quinic acid, and gallic acid in CDAE might be accountable for its anti-arthritic activity and safe use for a long period. [ABSTRACT FROM AUTHOR]

A wide range of experiments have yielded empirical evidence pertaining to the efficacy of medicinal plants in the therapeutic treatment of several disorders. However, the use of herbs without conducting a thorough assessment of their effectiveness and safety can lead to sudden or harmful consequences that may pose a risk to the overall health of internal organs. Therefore, the current investigation's goal was to determine the ethanolic extract of Litchi chinensis toxicological profile in rats. The Soxhlet extraction method extracted the fruit with ethanol as a solvent. The extract's susceptibility to acute, subacute, and subchronic toxicity was assessed. The histopathology of several organs (e.g., heart, liver, lungs, kidney and spleen) were also studied after treatment with plant extract. With the dosage of 2000 mg/kg, p.o., no deaths or adverse consequences were reported during the examination of acute toxicity. The Litchi chinensis extract produced no death or any observable changes in weight, behavior, organ weights, hematological or biochemical values in both oral subacute and subchronic toxicity experiments. Essential organs, including the heart, liver, lungs, kidney, and spleen, have regular planning when examined histopathologically, indicating no morphological changes. On the basis of results, the fruit (pericarp) extract of Litchi chinensis showed a lack of toxicity. [ABSTRACT FROM AUTHOR]

The Sungkai plant (Peronema canescens Jack) is widely used as an immunostimulant. This study determined the toxicity of the ethanol extract of Sungkai leaves in Wistar rats by histological evaluation of their kidneys. The study used 36 male rats administered ethanol extract of Sungkai leaves for 7, 14 and 21 days at three doses of 140, 280 and 560 mg/kg bw, respectively. In each group, three rats were taken to be sacrificed on days 8, 15 and 22, and their kidneys were exercised for further histological evaluation. The degree of kidney tissue damage and the ratio of kidney organs were noted. The descriptive results showed that the highest kidney damage was due to an extract dose of 560 mg/kg bw with a score of 2.2 in the mild damage category, which occurred at 21 days of administration. The observation of the ratio of kidney organs showed that there was a significant effect of variations in dose and duration of administration on the ratio of kidney organs (p<0.05). However, there was no significant effect on the interaction between dose and duration of administration on the ratio of kidney organs (p>0.05). [ABSTRACT FROM AUTHOR]

The use of honey as food and medicine is widespread, but insufficient data support that it is safe, especially when consumed in high doses. As a result, the present work aimed to investigate the potential toxicity using a repeated dose oral toxicity study. In the toxicity study, Wistar rats were divided into five groups, and orally administered with distilled water (control), 3, 6, 12, and 24 g/kg body weight (BW)/day of honey for 28 days in a row. Body weight, food consumption, clinical pathology, and histopathology were then examined. Significant suppression of body weight, food consumption, and body weight gain was observed at the dose of 24 g/kg BW in both sexes. Honey administration had no statistically significant effect on any of the haematological parameters. The clinical observations, blood coagulation and biochemical parameters, target organs, or histopathology did not reveal any additional nor other treatment-related adverse effects. Mild pathological changes in hepatic tissues were observed in the control, 12, or 24 g/kg BW dose groups, which were common spontaneous lesions unrelated to honey treatment. In the 24 g/kg BW group, one male rat showed non-specific reactions such as focal basophilic change of renal tubule cells, which were also regarded as spontaneous lesions. Based on these results, the no-observed-adverse-effect level (NOAEL) of honey in this repeat dose oral toxicity study was determined to be 12 g/kg BW in both sexes of Wistar rats. [ABSTRACT FROM AUTHOR]

Background and objectives: This study evaluated the acute and subacute toxicity of the Coriander Triphala tablet (CTT) in Wistar rats. Methods: The CTT was prepared according to the method described in our previous work. In the acute toxicity study, five female Wistar rats received 2000 mg/kg CTT and five female rats were administered distilled water as control. In the subacute test, sixty male and female rats were randomly divided into six groups. Three groups received 200, 500, and 1000 mg/kg of the tablet; the satellite group was treated with 1000 mg/kg of CTT, and controls received distilled water for 28 days. Body weights and food and water intake of rats were recorded. Toxicity signs were recorded and hematological, biochemical, and histopathological analyses were performed. Results: No remarkable toxic effect of the tablet was observed in the rats after receiving a single dose of 2000 mg/kg. This indicated that the median lethal dose (LD50) was more than 2000 mg/kg. In the subacute toxicity study, different doses of CTT didn’t change hematological parameters. However, the tablet increased the levels of cholesterol, creatinine, and aspartate aminotransferase (AST) in males and alanine aminotransferase (ALT) and AST in females at high doses. Histopathological evaluation of liver samples from both sexes showed congestion and hydropic degeneration of hepatocytes. Renal histopathology revealed varying degrees of tubular cell necrosis. Conclusion: Our data indicated the toxic effects of CTT on the liver and kidney, suggesting the need for special precautions in administration of this medication to the patients.

Abstract Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

Background: Leaves from Physalis angulata L. plant have been used as a source of traditional herbal medicine. However, toxicity studies on the P. angulata leaf (PAL) extract are limited. This study aimed to determine the subacute toxicity of the PAL extract on renal and liver functions and the associated histopathology. Methods: The PAL material was prepared by maceration, and the total flavonoid content of the ethanolic extract was determined, using spectrophotometry. Twenty female Wistar rats were divided into four groups of five each. The control group was untreated, but the other three groups received the PAL extract at 100, 500, or 1000 mg/kg, body weight. The subacute toxicity testing was performed over 28 days, and the toxicity symptoms were recorded daily. Results: The PAL extract contained a total flavonoid content of 22.47 mg/g quercetin. At 500 or 1000 mg/kg, the extract caused significant diarrhea in rats. There were no significant differences in the relative organ weights, or the serum levels of aspartate aminotransferase, alanine transaminase, urea, and creatinine. There was no significant damage in the kidneys and liver, but mild histological changes were evident in rats treated with 1000 mg/kg of the extract. Conclusion: The PAL extract did not cause renal or liver dysfunction in rats following 28 days of exposure. However, since diarrhea and mild histological alterations occurred in the liver and kidneys, precautions should be exercised when using the P. angulata extract at high doses in humans, especially over long periods.

Artemisinin-hydroxychloroquine sulfate tablets (AH) are regarded as a relatively inexpensive and novel combination therapy for the treatment of various forms of malaria, particularly aminoquinoline drugs-resistant strains of Plasmodium falciparum. Our aim was to conduct acute and subacute oral toxicity studies in non-rodents to obtain more nonclinical data on the safety of AH. Acute toxicity evaluation was performed in beagle dogs at single doses of 230, 530, 790, 1180, 2660, and 5000 mg/kg. Beagle dogs at doses of 0, 56, 84, and 126 mg/kg were used to assess subacute toxicity for 14 days. The approximate lethal dose range for acute oral administration of AH in dogs is found to be 790–1180 mg/kg, and toxic symptoms prior to death include gait instability, limb weakness, mental fatigue, tachypnea, and convulsion. Repeated doses of AH in dogs caused vomiting, soft feces, decreased activity, anorexia, and splenic red pulp vacuolation. Of note, AH could reduce body weight gain and prolong the QTc interval of individual dogs. Therefore, the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of oral administration of AH for 14 days in dogs are determined to be 84 mg/kg and 126 mg/kg, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Myrmecodia platytyrea, locally known as 'Sarang Semut', is an epiphytic plant native to Asia and the Asia Pacific. The tubers were traditionally used to manage cancer, hyperuricemia, and coronary heart diseases. Scientifically, the aqueous tuber extract has potential pharmacological benefits, including anti-cancer, anti-diabetic, and anti-inflammatory properties. Since the extract had no acute or subacute toxic effects, it might be used as a supplement to reduce inflammation and improve physiological functioning with better bioavailability than conventional preparations. This study aims to investigate the subacute toxicity of the microgranulated aqueous extract of M. platytyrea tuber (gMPAE). Methods: The formulation of the microgranules was established and analysed using a scanning electron microscope (SEM). The subacute oral toxicity study was carried out. The female nulliparous and non-pregnant ICR mice were divided into three groups (n=5), a group treated with normal saline (control group), a group treated with a placebo (blank microgranules), and a group treated with gMPAE, orally once daily for 28 days. Results: The gMPAE was produced using a spray-dry method and displayed microparticles with irregular shapes typical for spray-dried formulations. The sub-acute toxicity study showed no physical or behavioural changes in both placebo or gMPAE-treated mice compared to the control mice, with no mortality observed after 28 days of treatment and no signs of delayed occurrence of toxic effects 14 days post-treatment. Conclusion: Standardised spray-dried microgranules of M. platytyrea tuber aqueous extract were successfully developed to enhance the extract's efficacy and are safe to be used as health supplements. [ABSTRACT FROM AUTHOR]

This study was undertaken to screen for some biomarkers of toxicity in the liver of Nile tilapia fish during subacute Diazinon toxicity (0.28 mgL-1 for 25 days) by using Targeted metabolomics analyses and quantitatively measure 17 amino acids, and also to monitor antioxidant status of liver (glutathione peroxidase, catalase, superoxide dismutase and malondialdehyde). There were significant increases in branched chain amino acids valine, leucine and isoleucine (P>0.01, P>0.05 and P>0.01) respectively. There was a significant increase in phenylalanine (an aromatic amino acid) P>0.05, a significant increase in lipid peroxidation (malondialdehyde P>0.001), and significant decreases in the activity of antioxidant enzymes (SOD, CAT, GSH-px) with p values (P>0.01, P>0.01, and P> 0.001) respectively. Histopathological examination showed diffuse hepatocellular necrosis with multifocal granuloma and massive hepatocellular vacuolation with congested sinusoids. It can be concluded that subacute toxicity of DZN in Nile tilapia is involved in proliferation and growth of tumor cells and negatively affects the antioxidant status of the liver. [ABSTRACT FROM AUTHOR]

Sungkai plant (Peronema canescens Jack.) is an herbal plant that people widely use traditionally to treat various diseases. Sungkai is proven to have immunostimulant, antihyperuricemia, and antibacterial activities. Due to its widespread use and to ensure its safety, it is necessary to evaluate its toxicity. This study aimed to determine the effect of variations in dose and duration of administration of ethanol extract of Sungkai leaves (Peronema canescens Jack.) on SGPT and SGOT levels in male white mice. Thirty-six mice divided into four groups (a control group and three treatment groups) of nine each were used for this study. The control group received 0.5% Na CMC suspension, and the treatment groups (II-IV) were given the ethanol extract suspension of Sungkai leaves (Peronema canescens Jack.) at a dose of 200, 400 and 800 mg/kg BW p.o, respectively. The extracts were administered daily to the experimental animals for 7, 14, and 21 days. SGPT and SGOT levels were examined on days 8, 15 and 22 using a 5010 v5+ photometer. Data analysis was performed using the SPPS with a two-way ANOVA test based on variations in dose and duration of administration. The results of this study indicate that the ethanol extract of Sungkai leaves has no significant effect on SGPT and SGOT levels (p>0.05) based on variations in the dose and duration of administration. [ABSTRACT FROM AUTHOR]

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5 nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10 mg/kg bw was provided once a day for 14 days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines. [ABSTRACT FROM AUTHOR]

Only a small number of the many medicinally important species in the genus Psidium L. have had their safety assessed. Psidium glaziovianum, a plant native to Brazil, is reported to exert antinociceptive and anti-inflammatory effects; however, there are no apparent reports of long-term safety following administering of repeated doses. The aim of this study was to examine the effects of 28-day oral of treatment at 250, 500 or 1,000 mg/kg Psidium glaziovianum essential oil (PgEO) on behavioral and physiological parameters in male and female Swiss mice. First, PgEO was chemically characterized by gas chromatography mass spectrometry (GC-MS). The following parameters were examined: motor activity, body temperature, blood glucose, urine, hematology, biochemistry, histology, and oxidative stress. Characterization of PgEO revealed 48 components which were dominated by sesquiterpenes 1,8-cineol (24.29%), α-pinene (19.73%) and β-pinene (17.31%). Data showed that PgEO treatment in mice increased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) without markedly affecting body weight, hematological or biochemical parameters, as well as water or food consumption. Administration of PgEO in repeated daily dosages over 28 days did not significantly alter exploratory or locomotor activities. Based upon our findings, PgEO administration daily for 28 days, exhibited low toxicity and absence of effects on the nervous system. Data demonstrated that PgEO produced hypoglycemic and antioxidant actions which need to be considered in safety assessment. [ABSTRACT FROM AUTHOR]

Fenugreek (Trigonella-foenum-graecum.L) seeds are commonly utilized in cuisine as spices, in the traditional treatment and in the prevention of various troubles. This study attempts to assess the acute and subacute toxicity of its extract in wistar rats. In the acute toxicity, single oral administration of four doses (0,05 g, 0,3 g, 2 g and 5 g /kg.bw) to wistar rats was tested and to test subacute toxicity, quotidian oral administration of fenugreek seed extract at dosages of 1, 2 and 3 g/kg.bw was used for 28 days. The results of acute toxicity did not show any deaths and no indication of intoxication was observed in the rats for 14 days following receipt of the various doses of the extract. The subacute toxicity results demonstrated that repeated administration of the extract led to a significant weight gain (p<0.05) in treated rats in comparison to control rats. Treatment of rats with fenugreek seed extract did not cause any signs of intoxication and did not affect the hematological parameters of the rats compared to control rats (p>0.05). Gross examination revealed that the appearance of vital organs was not altered and histological examination revealed steatosis and an increase in the nuclei of hepatocytes in rats given a repeated dose of 3 g /kg of fenugreek seed extract. Fenugreek seeds extract is generally tolerated by rats even at high doses but more care should be taken at chronic use. [ABSTRACT FROM AUTHOR]

An indigenous Saharan species called Ephedra alata can be found in Algeria, North Africa, and other places. It has a wide range of applications in conventional medicine all around the world. So, the objective of the current investigation was to evaluate the safety of Ephedra alata's ethanolic extract (EEEA) through subacute oral toxicity in Swiss female mice. Mice received daily oral doses of the EEEA ranging from (250, 500, 1000, 2000, 4000, and 5000 mg/kg body weight) for 21 days. To assess the toxicity, the blood, as well as the primary organs (kidney, liver, brain, and heart), were collected and examined. No mortality or any clinical signs of intoxication were observed in treated mice. There were also no significant differences (p > 0.05) in body, kidney, brain, and heart weights, the majority of hematological parameters (HB, HT, RBC, WBC..), and biochemical parameters (PROT, CRE, URE, and TC). Furthermore, a significant (p > 0.05) decrease in liver weight, an increase in ALT, AST, LDH, and some histological alterations (with no hepatocyte necrosis) were observed in mice administrated relatively high doses of EEEA. This finding suggests a possible hepatotoxic effect of the EEEA particularly at high doses. From the study, EEEA can be used as a complementary treatment that helps to raise the antioxidants, as a stage that is used in the treatment of cancerous diseases. [Display omitted] • There are several therapies for breast cancer with adverse effects. • The use of natural sources became extremely important in cancer treatment. • Ephedra alata is an endemic Saharan species that grows in Algeria. • Evaluation of the sub-acute toxicity of EEEA is important for antioxidant study. • Oral administration of EEEA is safe at 1000 mg/kg. [ABSTRACT FROM AUTHOR]

Introduction: Moringa oleifera Lam has many pharmacological activities, such as immunostimulants. Aim: This study aims to determine the safety profile of repeated use and routine use of Moringa oleifera Lam on liver function and histology. Material and Method: This study used 36 male white rats as test animals. Moringa leaves were administered orally as standardised ethanol extract at doses of 7, 21, and 140 mg/kg BW for 21 days. The liver function observed was the activity of the ALT enzyme. On days 8, 15, and 22, three animals from each group had their blood collected through the orbital sinuses of the eyes and sacrificed to excise the livers. The parameters observed were ALT enzyme activity, liver ratio value, and histological damage of liver tissue. The two-way ANOVA was used to analyse the data of ALT enzyme activity and organ ratio values, followed by DMRT. In contrast, descriptive analysis was used to describe liver histological damage. Result: Test animals had no toxic symptoms or sudden death during the study. The results showed that ALT enzyme activity was significantly affected by the dose and duration of administration of the ethanol extract of Moringa leaves (p<0.05). However, on the organ ratio values, there were no significant effects of dose (p>0.05), but significantly affected by duration of administration (p<0.05). The liver histological descriptive analysis showed histological differences between the control and treatment groups. The 7 mg/kg BW and 21 mg/kg BW showed liver tissue with average to minimal damage. However, the dose groups at 140 mg/kg BW for 14 and 21 days showed changes in liver histology, although only minimal to mild impairment. Conclusion: It concluded that the administration of extract of Moringa oleifera Lam did not cause severe damage to the liver of white male rats. [ABSTRACT FROM AUTHOR]

Previous studies have shown that mice fed a diet containing 1% mantle tissue exhibited decreased food consumption and led to death. Toxic substances present in the mantle tissue have been isolated and identified. In the present study, we explored the characteristics and stability of mantle tissue toxicity. The treatment of mantle tissue with 1 mM hydrochloric acid, 1 mM sodium hydroxide, 1 mM dithiothreitol, and 1 mM hydrogen peroxide followed by heating did not significantly reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic conditions and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Mice fed a diet containing 20% mantle tissue did not show a distinct increase in toxicity compared with mice fed a diet containing 1% mantle tissue, demonstrating that feeding mantle tissue does not lead to acute toxicity. Finally, mantle tissue toxicity in the small intestine was examined. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time polymerase chain reaction analysis revealed that mantle tissue feeding caused changes in inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that mantle tissue feeding causes toxicity after initial damage to the small intestinal tissue. [ABSTRACT FROM AUTHOR]

The acute toxicity and subacute toxicity of an anthocyanins extract of Lycium ruthenicum (AEL) were evaluated. Acute oral toxicity test was performed in mice via intragastric administration of AEL 8 000 mg/kg once by a fixed dose method, and the toxicity responses of the mice were observed while their general states within 14 days were recorded. SD rats were selected for a 30-day feeding experiment, the changes of body weight and physical signs of rats were recorded during theadministration. At the end of the experiment, the biochemical indexes of urine, hematological indexes, and serum biochemical indexes were examined, the morphological changes in organs were observed, and the visceral body coefficient and visceral brain coefficient were calculated. The study revealed that in the acute toxicity test, no side effects was observed in mice, and their body weights increased normally with no obvious abnormalities detected in the anatomical organs. After continuous intragastric administration for 30 days, the rats in each experimental group showed no obvious toxic reaction, and their weights increased normally; Compared with the control group, the percentage of monocytes (M%) in the female high-dose group increased significantly (P<0.05) while their AST/ALT ratios decreased significantly (P<0.05); The serum Cl- and spleen coefficients of the male high-dose group were higher than those of the control group (P<0.05). The other urine biochemical indexes, hematological indexes, serum biochemical indexes, visceral coefficient and visceral brain coefficient of the rats in the experimental group did not show significant abnormalities. The results showed that the maximum tolerable dose for single intragastric administration of AEL to mice was not lower than 8 000 mg/kg, and no toxicity reaction was found in the rats after continuous intragastric administration for 30 days. AEL had no acute and subacute toxicities under the experimental conditions, exhibiting relatively high safety. [ABSTRACT FROM AUTHOR]

To provide reference for the safety consumption of Phyllanthus acidus (PA) as food and its further medicinal development and utilization, a comparative study on acute and short-termtoxicity and α-glucosidase inhibitory ability of different components of its branches and leaves was conducted. The crude extract of PA, prepared under aqueous ethanol reflux extraction, was partitioned successively with petroleum ether, ethyl acetate and N-butanol according to the polarity. Furthermore, an alcohol-eluted and water-eluted fractions were obtained from water-soluble residue by column chromatography. The half inhibitory concentration (IC50) of α-glucosidase was used as the evaluation index to compare the in vitro hypoglycemic activity of different extracts. The acute toxicity of these fractions was screened by maximum tolerated dose (MTD), median lethal dose (LD50) values, and their subacute toxicity was evaluated by continuous oral administration of samples for 20 days. The results showed that each component of PA had a certain inhibitory ability to α-glucosidase. The MTD of crude extract of PA was 2.0 g/kg, and the order of acute toxicity for different fractions was ethanol-eluted fraction>water-eluted fraction>petroleum ether fraction>ethyl acetate fraction>N-butanol fraction>crude extract. The main acute toxicity symptoms were startle followed by idling, writhing, and shortness of breath. Subacute toxicity test showed no obvious toxicity and lesions. It was indicated that it was safe to take 2 g/kg/d (equivalent to 8.6 g/kg of dried branches and leaves) of the whole component of PA at oral ingestion. Thus, they have the potential to be developed as hypoglycemic, weight-loss food and medicine.

Gardenia, as a medicinal and edible herb, has the pharmacological activity of protecting the liver and cholagogue, but the hepatotoxicity induced by the chemical component genipin (GP) limits its application. The aim of this study was to evaluate the acute and subacute hepatotoxicity of genipin in normal mice and mice with α-naphthalene isothiocyanate (ANIT)-induced liver injury. The results of the acute study showed that the LD50 of genipin was 510 mg/kg. Genipin exhibited hepatotoxicity in normal and jaundiced mice at doses of 125 mg/kg, 250 mg/kg, and 500 mg/kg, which increased with dose. In a 28-day subacute study, the 50 mg/kg and 100 mg/kg dose groups showed some pharmacodynamic effects at 7 days but exhibited hepatotoxicity that increased with time and improved after drug withdrawal. In addition, based on proteomics, the mechanism of liver injury induced by genipin may be related to the disruption of the UDP-glucuronosyltransferase system and cytochrome P450 enzyme activity. In conclusion, this study showed that genipin hepatotoxicity was time- and dose dependent, but it is worth mentioning that hepatotoxicity was reversible. It is hoped that this study will provide a scientific basis for circumventing the adverse effects of genipin.

Coptosapelta flavescens Korth. is one of the medicinal plants used as a traditional medicine in Vietnam for a long time. However, few documents proved its safety for a long time. Therefore, the study aimed to determine the toxicity effects of the aqueous extract of C. flavescens by determining its effects after subchronic oral administration in Swiss albino mice. The toxicity of C. flavescens extract was tested at doses of 400 and 1200 mg/kg, respectively, over 30 and 60 days on an in vivo model. Animal weight, behavior, and condition changes were monitored throughout the process. At the end of the observation periods, hematological indices and histopathological features of the animal specimens were analyzed. The administration of C. flavescens extract at doses of 400 and 1200 mg/kg caused a weight difference in male mice after 30 days and in both sexes after 60 days of administration compared to the control group. There were no significant changes in hematological parameters and biochemical indexes of the liver and kidney compared with the control group. The histological structure of the liver showed changes when treated with C. flavescens at both doses after 60 days, whereas the histological structure of the kidneys exhibited differences only at the dose of 400 mg/kg. Overall, the findings of this study indicate that Coptosapelta flavescens Korth. is unlikely to have subacute and subchronic oral toxicity. However, there are some minor effects on the liver and kidneys.

Opiates produce analgesia via G-protein signaling, and adverse effects, such as respiratory depression and decreased bowel motility, by β-arrestin pathway. Oliceridine, a G protein-biased MOR agonist, only presents modest safety advantages as compared to other opiates in clinical trials, possibly due to its limited bias. Our previous study shown that LPM3480392, a full MOR biased agonist, is selective for the Gi pathway over the β-arrestin-2. In the present article, we evaluated the subacute toxicity of LPM3480392 in rats. The rats were administered with control article or LPM3480392 0.6, 1.2 or 2.4mg/kg/day for 4 consecutive weeks followed by a 4-week recovery phase. Intravenous infusion was conducted at tail vein at 0.2, 0.4 or 0.8 mg/kg/day with a dosing volume of 10 mL/kg and 5 min/rat/dose, three times a day with an interval of approximately 4 h. The concomitant toxicokinetics study was conducted. Two unscheduled rats at 2.4 mg/kg/day died with no clear cause. For the scheduled necropsy, the major effects were associated with the MOR agonist-related pharmacodynamic properties of LPM3480392 (e.g., increased activity, increased muscle tone; decreased food consumption and body weight gain; and clinical chemistry changes related with decreased food consumption) in three LPM3480392 groups. In addition, LPM3480392 at 2.4 mg/kg/day also induced deep respiration and histopathology changes in testis and epididymis in sporadic individual rats. However, different from other opiates, LPM3480392 presents weak/no immunosuppression and the decreased adrenal gland weight, which may be due to LPM3480392' full MOR bias. At the end of recovery phase, all findings were recovered to some extent or completely. In the toxicokinetics study, the dose-dependent elevation of drug exposure was observed, which partly explained the toxicity of high dose. In summary, LPM3480392 has exhibited good safety characteristics in this subacute toxicity study in rats. [ABSTRACT FROM AUTHOR]

Introduction: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother‐to‐child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. Method: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28‐day feeding test was conducted to assess the potential subacute toxicity. Results: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose‐dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high‐dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high‐dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high‐dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high‐dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium‐ and high‐dose groups increased significantly (P < 0.05). Conclusion: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions. [ABSTRACT FROM AUTHOR]

The use of probiotics in animal husbandry ensures the maintenance of homeostasis of the digestive tract and prevents the development of factor infections in young animals – colibacteriosis, dyspepsia, and others, promotes the growth of animals with high survival rates. The main advantages of probiotics over chemotherapeutic drugs and antibiotics are that they are harmless to animal organism and are ecologically clean. In connection with the great attention paid to probiotics as ecologically safe drugs, the study of biological properties and the selection of bacterial strains, the most promising in the probiotic sense, are currently being intensified. This is the direction of the selection of species-specific strains for the intestinal biocenosis of a specific animal species, which have high colonization and antagonistic properties. Therefore, the development of the scientific basis for the creation of new probiotic preparations gave an impetus to their improvement and continued research in this direction. The aim of the work was to study the effect of the probiotic “Bioseven” on the intestinal biocenosis of white rats depending on the dose. Objectives of the study: to establish the toxicity of the drug “Bioseven” on laboratory animals with a single dose (“acute toxicity”) according to microbiological indicators; to investigate the toxicity of “Bioseven” on laboratory animals with long-term administration (“subacute toxicity”) according to microbiological indicators. Research work was carried out during 2022 at the department of veterinary and sanitary examination, hygiene of animal husbandry products and pathanatomy named after J. S. Zagaevskii. The toxicological characterization of the probiotic drug “Bioseven” (study of subacute and acute toxicity) was carried out under the conditions of the State Research Control Institute of Veterinary Medicines and Feed Additives (Laboratory of Pharmacology and Toxicology), (Lviv), the manufacturer of the drug was PP “BTU-CENTER” Ladyzhyn, Vinnytsia region. On the 31st day of use of the drug “Bioseven” (a feed additive with probiotic action) in a therapeutic dose, microorganisms of the genus Lactobacillus were sown 0.3 lg CFU/g more from the large intestine of experimental rats, microorganisms of the genus Bifidobacterium were sown at 0.5 lg CFU/g more than in the control group. The number of Candida fungi decreased by 0.6 lg CFU/g, and the total number of Escherichia coli – 0.2 lg CFU/g. When using the “Bioseven” probiotic in a 5-fold therapeutic dose, 0.5 lg CFU/g more microorganisms of the Lactobacillus genus and 0.6 lg CFU/g more Bifidobacterium microorganisms were sown from the large intestine of experimental rats than in the control group. At the same time, the number of Candida fungi decreased by 0.7 lg CFU/g, and the total number of Escherichia coli to 0.4 lg CFU/g. Under the conditions of use of the drug “Bioseven” in a 10-fold therapeutic dose, microorganisms of the genus Lactobacillus were sown from the large intestine of experimental rats, 0.9 lg CFU/g more, microorganisms of the genus Bifidobacterium 1.2 lg CFU/g more than in the control the group At the same time, the number of Candida fungi decreased by 1.1 lg CFU/g, and the total number of Escherichia coli by 0.8 lg CFU/g. Prospects for further research consist in the study of the impact of the biotic drug “Bioseven” on indicators of metabolic processes and productive qualities of farm animals. [ABSTRACT FROM AUTHOR]

Laboratory studies were conducted to determine the subacute toxicity and tolerance of the veterinary drug “BTF plus” on white rats, dogs, and guinea pigs. The “BTF plus” preparation is a complex vitamin and mineral preparation based on butophosphane, L-carnitine, and cyanocobalamin, which normalizes and corrects metabolic processes in animals and poultry. The drug is used for various types of animals and poultry as a stimulating, tonic and general strengthening agent for obstetric pathologies (difficult births, postpartum complications, paresis, eclampsia, sexual cycle disorders); metabolic disorders caused by irrational feeding, malnutrition, asthenic syndrome, etc.; anemia with helminthiasis; secondary anemias, as an additional means in the treatment of magnesium and calcium deficiency; to increase muscle activity, with significant loads, overstrain and exhaustion in animals; to increase the body's resistance to various pathogens; to stimulate growth, development and live weight gain in young animals and poultry; as an additional means in the treatment of diseases caused by various factors (infectious and non-infectious origin). When administered subcutaneously to rats, the drug “BTF plus” under the conditions of a subacute toxicological experiment in doses (by absolute weight of the drug) of 200.0, 1000.0, and 2000.0 mg/kg of body weight does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, but on the contrary, stimulates hematopoietic processes and has a positive effect on metabolic processes in their body. Subcutaneous administration of the drug “BTF plus” to dogs in doses (by absolute weight of the drug) of 200.0, 1000.0, and 2000 mg/kg of body weight for ten days does not cause hepatotoxic and nephrotoxic effects on the body under the conditions of a subacute toxicological experiment, but on the contrary, stimulates hematopoietic processes and has a positive effect on metabolic processes in the body of target animals. The tolerance of guinea pigs to the drug “BTF plus” was studied. It was established that the drug does not hurt the body and behavior of ants when administered subcutaneously in doses (based on the absolute weight of the drug) (5000,0–15000,0) mg/kg of body weight. Further studies will be the next stage of pre-registration tests aimed at studying the embryotoxic and carcinogenic effect of “BTF plus”, which is mandatory material of the “Safety and residue studies” section of the dossier for this medicinal product [ABSTRACT FROM AUTHOR]

Meloxicam, a non-steroidal anti-inflammatory drug (NSAID) for the treatment of osteoarthritis. Despite being more effective against pain mediated by inflammation, it is associated with gastrointestinal, cardiovascular, and renal toxicity. In the current study, acute single-dose (2000 mg/kg) and subacute (500, 1000, and 2000 mg kg−1 for 28 days) dermal toxicity analyses of meloxicam emulgel were conducted in Wistar rats. Various biochemical, hematological, histopathological and immunohistochemical parameters were evaluated. The dermal LD 50 (lethal dose) of meloxicam emulgel was found to be > 2000 mg/kg. No significant adverse effects of meloxicam emulgel following topical administration in subacute toxicity studies were noticed. IL-1β was not expressed post treatment with meloxicam emulgel. IL-1β is an influential pro-inflammatory cytokine that is decisive for host-defence consequence to injury and infection. Therefore, using data gleaned from the extant study, topical administration of meloxicam emulgel may be regarded as safe as the "no observed adverse effect level" (NOAEL) was >2000 mg/kg in experimental animals. [Display omitted] • Meloxicam emulgel did not exhibit any clinical symptoms in acute toxicity study. • Meloxicam emulgel did induce any toxicity in repeated dose toxicity study. • Meloxicam emulgel did not induce any irritation and erythema multiforme in skin. [ABSTRACT FROM AUTHOR]

Vernonia cinerea (L.) Less is a medicinal plant distributed throughout India and is used traditionally for treating several diseases. This study aimed to analyze the toxicological effects of ethyl acetate extract (VCEA) of this plant. Preliminary phytochemical screening of VCEA was conducted by conventional methods. For acute toxicity studies, female Swiss albino mice were treated with a single oral dose of 2000 mg/kg body weight of VCEA and observed for any changes in general characters. For the subacute toxicity study, mice were treated (50 or 100 mg/kg body weight) consecutively for 28 days and the haematological, biochemical, and histopathological changes were analysed. From the phytochemical analysis, it was inferred that terpenoid content was more in the VCEA extract. No mortality or toxic effects were observed in the acute study. Repeated dosage of VCEA at 50 mg/kg body weight did not impart any adverse effects in any of the parameters assessed. The higher dosage (100 mg/kg body weight) made the animals slightly anaemic. Therefore a dose of up to 50 mg/kg body weight is recommended as safe for testing the pharmacological properties of VCEA in mice models. [ABSTRACT FROM AUTHOR]

Objective: To assess the acute and subacute toxicity as well as the phytochemical composition of two extracts and three fractions of Ammi majus L. Methods: The aqueous extracts were prepared separately by maceration for 48 h and by infusion for 1 h, while the fractions were prepared by the Soxhlet extractor, successively employing cyclohexane, ethyl acetate, and ethanol. The acute toxicity study was carried out in accordance with the OECD N°423 guideline at a single dose (2000 mg/kg) in mice for 14 days. The subacute toxicity study was performed by a daily oral administration of 250 mg/kg for 10 days and 100 mg/kg doses for 28 days. Phytochemical screening was performed using staining and precipitation reactions, while the chemical characterization of some analytes was detected by HPLC-MS/MS analysis. Results: In the acute toxicity study, no signs of toxicity such as convulsion, salivation, diarrhea, sleep and coma were observed during 30 minutes and 14 days, so the lethal dose was higher than 2000 mg/kg for each extract and fraction. The subacute toxicity results showed that at a dose of 250 mg/kg, 61.10% of the animals died and the rest developed morbidity. On the other hand, at a dose of 100 mg/kg, all the animals were still alive after 28 days, with no morbidity and the biochemical parameters were normal with no abnormalities in the liver, kidneys and pancreas. Phytochemical screening indicated the presence of flavonoids, tannins, coumarins, and free quinones and the absence of alkaloids and anthocyanins. Conclusions: The extracts and fractions of Ammi majus L. are not toxic in the short and long term with a varied chemical composition. Toxicological tests on animals other than rodents and in the long term (more than 28 days) are needed to further confirm the safety of Ammi majus extracts.

Background: Fumaria officinalis is largely used in traditional medicine due to its efficiency in the treatment and prevention of numerous diseases and its large spectrum of therapeutic effects. Its multiple beneficial properties are due to its richness in bioactive substances, particularly isoquinoline alkaloids. However, few studies have addressed the toxicity of this plant. Objectives: The present work aimed to study acute and subacute toxicity of alkaloids extracted from F. officinalis using Swiss albino mice as the in vivo model. Methods: Alkaloids from the aerial parts of F. officinalis were extracted and administered to male and female Swiss albino mice. The acute and subacute toxicities were studied by monitoring the weight and histopathological study of animal bodies and organs (e.g., liver, heart, spleen, and kidneys). Results: The results revealed that mice treated with increasing doses developed serious symptoms of toxicity (i.e., respiratory problems, tremors, coma, and paralysis leading the death) and lost weight. The LD50 was estimated at 1341.11 mg/kg permitting its classification as a low-toxic plant. The microscopic observations demonstrated disturbances in the kidney and liver, but not the heart and spleen. Conclusion: The alkaloids of the aerial parts of F. officinalis expressed severe toxicity in mice, particularly at high doses. Nevertheless, the neutral fraction of alkaloids is more indicated.

Abstract Background Jintiange capsule is composed of bionic tiger bone powder and has similar ingredients to natural tiger bone. Objective To characterize the subacute toxicities of Jintiange capsule in rats and beagle dogs for preclinical safety assessment. Methods Suspensions of Jintiange capsule were given via gastric lavage over a 26‐week period at low (500 mg/kg), mid (1500 mg/kg) and high doses (4000 mg/kg) in SD rats. Beagles were given by gastric lavage of suspensions of Jintiange capsule once daily for 6 days per week for 39 weeks at low (300 mg/kg), mid (900 mg/kg) or high dose (2000 mg/kg). Results Repeated gastric lavages of suspensions of Jintiange capsule at doses from 500 to 4000 mg/kg over 26 weeks caused no significant toxicity (No Observed Adverse Effect Level, NOAEL) in rats. In addition, repeated gastric lavages of suspensions of Jintiange capsule at doses from 300 to 2000 mg/kg over 39 weeks caused NOAEL in beagles. Conclusions Jintiange capsule was safe in rats at a dose 66.7 times the clinically recommended dose and in beagles at 33.3 times the clinically recommended dose. Our subacute toxicity studies in rats and beagles demonstrated no apparent overall toxicities including haematotoxicities, hepatotoxicities and renal toxicities.