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Dacryodes edulis (G. Don) H.J. Lam) is the most popular species under the genus Dacryodes. It is well known for its nutritional and ethno-medicinal uses in South-eastern and South-western Nigeria. This study was aimed to evaluate the toxicity of the aqueous-methanol fraction of crude methanol extract of Dacryodes edulis leaves (AMDE). The test rats were randomized to groups of single oral treatment of AMDE (10−5000 mg/kgbw) for the acute toxicity study. They were monitored for obvious signs of behavioural change and mortality. For the subacute toxicity study, the rats were randomized to three daily treatment groups (of 200, 400 and 600 mg/kgbw of AMDE) for 28 days. The fourth group (control) received 2.5 %v/v DMSO. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. The histopathology of the livers and kidneys were assessed using the excised organs. The cytotoxicity and genotoxicity of AMDE were also evaluated using Allium cepa model. The result showed that acute administration of AMDE, up to a dose of 5000 mg/kgbw did not result in mortality of the test rats. The observed median lethal dose (LD50) was greater than 5000 mg/kgbw. The subacute oral administration of AMDE for 28 days showed no significant (p > 0.05) effect on liver function, kidney function indices, organ - body weight ratio, but significantly (p

Objective: The present study aimed to investigate the acute and subacute toxicity profile of fucoidan obtained from Sargassum wightii Greville, a brown marine algae in order to assess its safety. Methods: Fucoidan was isolated from Sargassum wightii Greviile and subjected to FTIR analysis to confirm the functional groups. In acute toxicity study, a single dose of fucoidan (2000 mg/kg) was orally administered to three female rats as per OECD guideline 423. OECD guidelines 407 was adopted for subacute toxicity study. Fucoidan was orally administered to male and female rats at doses of 100, 200 and 400 mg/kg. Hematological, biochemical and histopathological analyses were carried out. Results: FTIR analysis confirmed the presence of major functional groups. The animals did not show any remarkable toxic signs or mortality in acute toxicity study at single oral administration of fucoidan at the dose of 2000 mg/kg bodyweight. In subacute toxicity, no statistically significant difference in body weight, relative weight of vital organs, food and water intake compared to the control group was observed. Serum glucose and cholesterol showed a statistically significant reduction at all the doses when compared to normal control and the reduction was in a dose dependent manner. There were no other changes observed in biochemical or haematological parameters. Histopathological analysis showed no significant toxic signs at organ levels in treated groups when compared to normal control. Conclusions: Based on the results obtained from acute and subacute toxicity study, fucoidan is considered to be safe in the models tested, which encourages its long term administration for medicinal uses. This study supports the application of fucoidan as a traditional medicine.

Anacardic acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing anacardic acid (9.375 μg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated anacardic acid at 2.25 and 112.5 μg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs’ relative weight reductions. Blank and anacardic acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD50) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30–80 nm. The LD50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.

Evaluation of toxicity induced in laboratory animals is paramount to the screening step in the assessment of the safety profile of all compounds. 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative has been investigated due to its pharmacological properties, including its antinociceptive and anti-inflammatory. However, the safety profile of this compound is yet to be determined. The present study seeks to highlight the toxicity effect of this compound using acute and subacute toxicity studies in the mice model. A single highest dose (1000 mg/kg) and repeated dose (0.1, 0.5, 1, 5 and 10 mg/kg) of DMPF-1 supplementation were executed. All toxicity study performed was supported by behavioural and body weight changes, haematological, serum biochemical analysis, macroscopic and microscopic analysis of the vital organs. The present result simplifies that DMPF-1 compound supplementation for four weeks is non-toxic as it caused no significant alteration in mice body weight and behaviour. Besides, no significant changes in haematological and biochemical parameters were observed. Further evaluation of its safety profile was confirmed by the normal architecture of the tissues organs obtained. Collectively, this report showed that DMPF-1 was safe to be consumed. [ABSTRACT FROM AUTHOR]

Introduction: The bark of Bois Bande (Parinari campestris) is a popular aphrodisiac in the Caribbean that has been traditionally used for many years to restore sexual vitality, increase sperm count, and treat erectile dysfunction, without valid scientific data. Acute and 28-day subacute toxicity studies were conducted to evaluate the safety of the hydroalcoholic extract of P.campestris bark and to find a safe dose for human use in conventional medicine. Methods: The acute toxicity study used a single oral dose of P.campestris extract at four separate doses, 5, 50, 300, and 2,000 mg/kg, and was seen for 14 days, while the subacute toxicity study used a daily oral dose of P.campestris extract at 3 different doses, 100, 300, and 1000 mg/kg/day for 28 days. Results: The LD50 of P.campestris extract was found to be greater than 2000 mg/kg in the acute toxicity study. P.campestris extract did not show toxicity at 1000 mg/kg/day in subacute toxicity trial; NOAEL was 1000 mg/kg/day in rats. However, the body weight was increased in males. Conclusion: In conclusion, 1000 mg/kg P.campestris extract can be considered safe and non-toxic in males. [ABSTRACT FROM AUTHOR]

Background: Vitex doniana Sweet fruit, an under-utilised crop specie of Ghana, has not been validated for its ethnomedical use in managing inflammatory conditions. Therefore, the study sought to investigate its anti-inflammatory and antioxidant activities as well as isolate and quantify one of its active constituents. Materials and methods: In-vivo anti-inflammatory activity of the methanol fruit extract was evaluated using the carrageenan-induced oedema model in chicks. The in-vitro antioxidant property was also investigated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The acute and subacute toxicity studies of the fruit extract were evaluated in rodent models. Results: No signs of autonomic and central nervous system stimulation/depression were recorded. The LD50 by oral route, was estimated to be beyond 3000 mg/kg. Subacute studies revealed an increase in red blood cell and lymphocyte counts. Liver enzymes, serum proteins and bilirubin levels did not significantly increase. The crude extracts at doses of 10, 30 and 100 mg/kg inhibited paw oedema considerably. The ethyl acetate fraction showed the highest antioxidant activity (IC50 = 99.35 ± 0.77 μg/mL). Oleanolic acid, isolated from the ethyl acetate extract, showed significant anti-inflammatory and antioxidant activities. A sensitive high-performance liquid chromatography method for the detection and estimation of oleanolic acid, as a biomarker compound for V. doniana fruit, was developed and validated for quality assurance purposes. Conclusion: The extract of V. doniana fruits possesses considerable anti-inflammatory and antioxidant properties and was non-toxic under laboratory conditions.

Fluorescent gold nanoclusters conjugated with α-lipoic acid (FANC) is a promising biocompatible fluorescent nanomaterial with a high potential for drug development. However, there is still no FANC-related research on toxicology, which is very important for future research and the development of healthy food supplements or drugs. This study uses oral administration of FANC to determine the most appropriate dose range in ICR mice for further evaluation. The in vivo acute and subacute toxicity study was conducted by oral administration of FANC to male and female ICR mice. Animal survival, body weight, daily food consumption, hematological profile, organ coefficient, serum biochemistry profile, and histopathological changes were analyzed. FANC did not show any form of morbidity or mortality at acute and subacute toxicity in both male and female ICR mice. Animal behavior, daily food consumption, hematological profile, organ coefficient, and histopathology showed no treatment-related malignant changes at single and repeated doses. Furthermore, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine (CRE) levels showed no significant malignant changes, which indicated that FANC does not cause liver and renal damage. The only change observed in this study was the change in body weight. The body weight of the FANC-treated group was slightly decreased in female mice but increased in male mice; however, the body weight decreases were below the threshold of concern, and there was no dose–response effect. In conclusion, no observed adverse effect level (NOAEL) in repeated doses was considered in 20 μM/100 μL/25 g male and female ICR mice.

The present study aimed to evaluate the acute and subacute toxicity profiles of Erodium guttatum extracts in mice using the methods described in the guidelines of the OECD. In the acute toxicity study, the LD50 value was greater than 2000 mg/kg. The subacute toxicity study of E. guttatum extracts showed no significant changes in body or organ weights. The administration of E. guttatum extracts to mice at a dose of 200 mg/kg led to an increase in white blood cells, platelets and hemoglobin. Moreover, the aqueous extract of E. guttatum only decreased liver aspartate aminotransferase (ASAT) levels at a dose of 200 mg/kg, and creatinine and urea levels did not show any significant alterations compared to the control group. Our results showed that the extracts of E. guttatum caused a slight increase in alanine aminotransferase (ALAT) and triglycerides. The histological study showed that mice treated with E. guttatum extracts experienced some histopathological changes in the liver, particularly with the methanolic extract, and slight changes in the kidneys and pancreas. Regarding the renal profile, no toxicity was observed. These results provide basic information on the toxicological profile of E. guttatum used in traditional medicine.

Background: Biosynthesized silver nanoparticles (AgNPs) are widely used in various biomedical applications. However, limited reports are currently available about the safety of biofabricated AgNPs using Cinnamomum zeylanicum bark extracts. Objectives: The current study is aimed to assess the potential toxicity of biosynthesized AgNPs (using C. zeylanicum) by subacute oral administration in experimental rats. Methods: AgNPs were biofabricated using methanol extract of C. zeylanicum bark and characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Twenty-four Rattus norvegicus female rats were divided into 4 groups (6 animals per group) as follows: Group-I was the control, while groups II, III, and IV were given 0.85, 1.76 and 3.53 mg/kg doses of AgNPs, respectively for 14 consecutive days. After 14 days of oral administration of AgNPs, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured using an ELISA technique. Serum concentrations of urea, creatinine, aspartate transaminase (AST) and alanine transaminase (ALT) were also determined as well as histopathologic features of the liver and the kidney. Results: AgNPs did not induce any changes in mean body weight, biochemical parameters (AST, ALT, urea and creatinine), oxidative stress biomarkers (MDA, SOD and CAT) and histopathologic features (of the liver and kidneys) of the treated groups when compared to control group. Conclusions: Our findings suggest that the oral administration of biogenic AgNPs (biofabricated using methanol extract of C. zeylanicum) to rats at a specific dose is relatively safe and does not show any signs of toxicity.

Carissa spinarum L. (Apocynaceae) is used traditionally, in Africa, to treat many diseases such as malaria, sickle cell anemia, epilepsy, helminthoses, and sexual weakness. The aim of this study is to investigate the cytotoxicity on Artemia salina, the acute and subacute (28 days) oral toxicity of C. spinarum hydroalcoholic root extract on Wistar rats. The cytotoxicity was performed on A. salina larvae. The acute and subacute toxicity was performed using Organization of Economic Cooperation and Development guideline. Malondiadehyde as lipoperoxidation marker was evaluated and expressed according to tissue proteins. The cytotoxicity has shown that the lethal concentration 50 (LC50) was 0.9 mg/mL. The limit test dose of 5000 mg/kg did not provoke death or toxicity signs. For the subacute toxicity, no signs of toxicity or mortality were observed during the experiment. Results of biochemical and hematological parameters have not shown any treatment-related abnormalities, except a significant decrease of alkaline phosphatase at 1000 mg/kg (P < .05) and an increase of chloride ion level at 500 mg/kg (P < .01). There was no significant difference between the treated group and the control group concerning the malondialdehyde concentration, the body weight, and the organs relative weight (P < .05), except for testis at 500 mg/kg (P < .05). According to our results, the hydroalcoholic extract of C. spinarum roots is safe when administrated at 500 mg and 1000 mg/kg to Wistar rats for 28 days. [ABSTRACT FROM AUTHOR]

Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and β-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated. This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice. The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study. Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC 50 μg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p < 0.05) increase in liver enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The histopathological score showed mild hepatocellular necrosis in administering 250, 500, and 1000 mg/kg of MLE. The parameters of renal injury were within normal limits, with the increase in eosinophilic cytoplasm observed in the histological scoring at 1000 mg/kg of MLE. Morus alba leaf extract showed abundant polyphenols. In a study on subacute toxicity, MLE caused mild hepatotoxicity in mice. The toxic effect of the extract may be due to kaempferol and chlorogenic acid compounds. The 125 mg/kg MLE dose was safe with no adverse effects. [Display omitted] • MLE contains more flavonoid compounds than phenolic acid. • Chlorogenic acid was documented as the primary compound. • MLE caused mild hepatotoxicity correlated with kaempferol and chlorogenic acid. • 125 mg/kg MLE dose was safe with no adverse effects. [ABSTRACT FROM AUTHOR]

Panchvalkala is a conventional Ayurvedic medicine used as a douche in gynecological disorders such as leucorrhea, infertility, and endometriosis. Recently, we have reported the anticancer activity of Panchvalkala aqueous extract (PVaq) in cervical cancer cell lines, SiHa (HPV16+), HeLa (HPV18+), and mouse papilloma models. Here, we have evaluated the safety of the aqueous extract of Ayurvedic formulation, Panchvalkala (PVaq), in Swiss albino mice by performing subacute toxicity study. Male and female Swiss albino mice (n = 5/sex/group) were gavaged orally with different doses of PVaq for 28 consecutive days. The mice were distributed into six groups: I (vehicle control), II (vehicle control reversal), III (PVaq 250 mg/kg), IV (PVaq 500 mg/kg), V (1000 mg/kg) and VI (1000 mg/kg high dose reversal). Animals were observed periodically to record any clinical signs of toxicity or mortality. After completion of treatment and recovery periods, animals were evaluated for the effect of PVaq on urine parameters, followed by hematological and biochemical parameters. Animals were sacrificed on day 29 for gross observation of vital organs and to study their histopathology. Reversal groups were maintained for further 14 days to observe any delayed onset of toxic side effects or reversal of toxicity, followed by sacrificing the mice on day 43. In the subacute toxicity study, PVaq did not show any significant change in food, water consumption, and body weights. There were no significant alterations in hematology, biochemistry, urine parameters, and histopathology of the analyzed tissues (brain, heart, liver, lung, spleen, thymus, kidney, epididymis/ovaries, and testis/uterus). The parameters were comparable to their respective controls in both the female as well as the male mice groups. Upon macroscopic and microscopic observation of vital organs, no abnormality was detected compared to the respective control groups. The subacute toxicity study demonstrated that oral administration of PVaq was safe in female and male Swiss albino mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Dysphania ambrosioides (L.) Mosyakin and Clemants is a medicinal plant that has traditionally been used to cure a range of diseases. There has been no thorough investigation of the potential toxicity of this plant. The objective of this study is to assess the acute and subacute toxicity of D. ambrosioides hydroethanolic extract (DAHE), as well as it alkaloids composition, utilizing LC-MS/MS analysis. An in silico approach was applied to determine pharmacokinetic parameters and to predict the toxicity of D. ambrosioides identified alkaloids. A 14-day treatment with a single oral dose of 1–7 g/kg was carried out to investigate acute toxicity. DAHE was given orally at dosages of 5, 50, and 500 mg/kg for 15 days in the subacute toxicity investigation, and body weight and biochemical parameters were evaluated. Livers, kidneys, lungs, and heart were examined histologically. Chromatographic investigation revealed the existence of nine alkaloids, with N-formylnorgalanthamine being the most prevalent. The oral LD50 value of DAHE was found to be 5000 mg/kg in an acute toxicity study. No variations were observed with respect to food intake, water consumption, mortality, or body and organ weight in the subacute toxicity study. On the other hand, DAHE (500 mg/kg) significantly enhanced alanineaminotransferase, aspartate aminotransferase, and urea. Liver and kidney histological examinations revealed modest infiltration of hepatocyte trabeculae by inflammatory cells in the liver and slight alteration in the kidney histoarchitecture. According to our findings, DAHE exhibits low to moderate toxicity.

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD50. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

Maduramicin, an extensively used anticoccidial drug, has been introduced into environment due to poorly absorbed in the intestine of broiler chicken. To understand the potential ecological toxicity of maduramicin on aquatic organisms, acute and subacute toxicity, hemolymph biochemistry, histopathology and the expressions of drug metabolism and stress response genes of crayfish (Procambius clarkii) were investigated in this study. For the first time, the 96 h median lethal concentration (LC50) of maduramicin on crayfish was 67.03 mgL−1 with a 95% confidence interval (54.06–81.32 mgL−1). Then, the crayfish were exposed to 0.7 mgL−1 (1/100 LC50), 3.5 mgL−1 (1/20 LC50) and 7.0 mgL−1 (1/10 LC50) maduramicin for 28 days. Maduramicin significantly altered biochemical parameters including AST, ALT, CK, LDH and ALP of hemolymph in crayfish at several time points. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of crayfish gills, hepatopancreas and abdominal muscle were significantly decreased or elevated by different concentrations of maduramicin treatment at varying time points. Furthermore, histopathological damage of crayfish gills, hepatopancreas and abdominal muscle were observed in a concentration-dependent manner. The expressions of metabolic and stress response genes (CYP450, GST, COX1, COX2, HSP70 and MT) in hepatopancreas of crayfish were significantly up-regulated by maduramicin (7.0 mgL−1) treatment for 8 h to 7 d, and returned to normal levels after the removal of maduramicin for 3–7 days. In conclusion, our findings demonstrated that environmental exposure of maduramicin threaten to the health of crayfish living in the areas nearby livestock farms or pharmaceutical factory. Crayfish exhibited resistance to the stress of maduramicin via activating drug metabolite and detoxification pathways.

Taurodeoxycholate (TDCA) inhibits various inflammatory responses suggesting potential clinical application. However, the toxicity of TDCA has not been evaluated in detail in vivo. We investigated the acute toxicity and 4-week repeated-dose toxicity of TDCA following intravenous infusion under Good Laboratory Practice regulations. In the sighting study of acute toxicity, one of two rats (one male and one female) treated with 300 mg/kg TDCA died with hepatotoxicity, suggesting that the approximate 50% lethal dose of TDCA is 300 mg/kg. Edema and discoloration were observed at the injection sites of tails when rats were infused with 150 mg/kg or higher amount of TDCA once. In 4-week repeated-dose toxicity study, no treatment-related mortality or systemic changes in hematology and serum biochemistry, organ weights, gross pathology, or histopathology were observed. However, the tail injection site showed redness, discharge, hardening, and crust formation along with histopathological changes such as ulceration, edema, fibrosis, and thrombosis when rats were infused with 20 mg/kg TDCA. Taken together, TDCA induced no systemic toxicity or macroscopic lesions at the injection site at a dose of 10 mg/kg/day, which is 33 times higher than the median effective dose observed in a mouse sepsis model. These findings suggest that TDCA might have a favorable therapeutic index in clinical applications. [ABSTRACT FROM AUTHOR]

Syzygium polyanthum (Wight) Walp. var. polyanthum (serai kayu) leaves is a popular herb and widely used in traditional medicine. Despite the ethnomedicinal benefits, very limited studies have researched on the toxicity of this plant. The aim of the present study was to investigate the potential effects of methanolic extract of Syzygium polyanthum (MESP) leaves via 28-day repeated oral dosing in Sprague Dawley rats. MESP leaves was administered at doses of 0 (control), 400, 1000 or 2000 mg/kg to an equal number of male and female rats (n = 10/group). Results obtained indicated that MESP did not affect the general conditions (body weight, feed intake and oestrous cycle) and apparent behavioural changes of the rats. Biochemical parameters revealed a slight significant variation in the aspartate aminotransferase (AST) level between the male rats treated with the lowest and highest doses of MESP, but these findings were both statistically insignificant when compared to the control group. The liver of the males (dose 1000 and 2000 mg/kg/day) also exhibited histoarchitectural defects on the hepatocytes and cytoplasm when compared to those of the control group. In contrast, female rats did not encounter any significant findings in all parameters tested. In conclusion, this study suggests that the MESP leaves might exhibit sex-based variation effects and thus, the use of this extract particularly at higher doses should be thoroughly considered. [ABSTRACT FROM AUTHOR]

Phytochemical analyzes of the mixture were carried out by an assay by HPLC-DAD. The subacute toxicity studies were carried out by oral administration for 28 days, then the evaluations of the relative organ weights, biochemical, hematological, and histopathological analyzes were studied. The analyzes by HPLC-DAD showed the presence of gallic acid, chlorogenic acid, syringic acid, coumaric acid, sinapic acid, 4-Hydroxyphenylacetaldehyde, 3, 4 hydroxycinnamic acid and rutin. The assessment of subacute toxicity presented a statistically significant decrease in body weight and in the relative organ weight of rats treated with the dose of 500 mg / kg. After analyzing the biochemical and hematological parameters, the aqueous extract of the mixture showed functional renal and hepatic toxicity. Histologically, oral administration of the aqueous extract of the mixture at dose of 500 mg / kg showed a histological hepatic change, while the renal tissue presented no change. [ABSTRACT FROM AUTHOR]

Sodium taurodeoxycholate (TDCA) has been investigated for various inflammatory disorders such as sepsis. We recently evaluated nonclinical safety profile of TDCA using rats infused intravenously. As a series of preclinical safety investigations, we further conducted toxicity studies with TDCA delivered to dogs via intravenous administration under Good Laboratory Practice regulation in this study. In dose range-finding study (dose escalation study), dogs given with TDCA at a dose of 150 mg/kg showed marked changes in clinical signs, hematology, and serum biochemistry. And biochemical markers of liver damage and local skin lesions were observed following intravenous infusion of 100 mg/kg TDCA, suggesting that 100 mg/kg was chosen as the highest dose of TDCA for 4-week repeated-dose toxicity study using dogs. Despite no treatment-related significant changes in body weight, food consumption, ophthalmoscopy, and urinalysis, skin lesions were observed at the injection site of animals administered with higher than 50 mg/kg of TDCA along with biochemical and histopathological changes associated with liver injury. However, most of off-target effects were found to be reversible since these were recovered after stopping TDCA infusion. These findings indicate that the no-observed-adverse-effect-level (NOAEL) for TDCA in dogs was considered to be 5 mg/kg/d. Taken together, our results provide important toxicological profiles regarding the safe dose of TDCA for drug development or clinical application. [ABSTRACT FROM AUTHOR]

Pomegranate (Punica granatum L.) is a fruit used extensively in traditional medicine by ancient and modern cultures. Different parts of the tree and fruit, such as leaf, peel, pericarp, aril, seed, and juice contain considerable amounts of phenolic compounds with high antioxidant activities. To improve its storability, pomegranate juice was microencapsulated by spray drying. The present study evaluated microencapsulated pomegranate juice (MPJ) for toxic effects in Wistar rats and CD-1 mice to determine if MPJ can be considered safe for human consumption and used as a nutraceutical. No deaths or deleterious effects occurred when high doses of 5000 mg/kg were orally administered in rats for 14 days, indicating an absence of subacute toxicity. Similarly, 3000 mg/kg MPJ administered to CD-1 mice for 90 days did not show subchronic toxicity. In fact, MPJ resulted in lowered weight gain in both rats and mice. Cytotoxic and microbiological analyses of MPJ were also performed. MPJ did not cause any cytotoxicity in epithelial cell culture as tested using the Alamar blue assay. Additionally, histopathological analysis of kidney and liver corroborated the absence of toxicity in CD-1 mice. The microbial load of the MPJ was low, and no pathogenic bacteria were present. In conclusion, the results reported here show that high doses of MPJ are apparently innocuous in rats and mice for the 14 and 90 days investigated, respectively. Although preliminary, our results suggest that MPJ may be safe to ingest and may even have beneficial effects in reducing weight gain. Graphical Abstract [ABSTRACT FROM AUTHOR]

Qing Hao Gan Cao (QHGC), a Chinese medicinal formula containing Artemisia annua and Glycyrrhizae Radix et Rhizoma, has been used to treat sunstroke and as an antiviral agent for more than 800 years. It has not previously been subject to a toxicological safety evaluation in acute and subacute (28 days) studies. Therefore, the acute and subacute toxicity of an aqueous extract of QHGC were evaluated in vivo. For the QHGC preparation, the botanical raw materials were crushed into pieces and mixed in the ratio of 10:1 in distilled water for 12 h, then boiling three times for 2 h each time. The three decoctions were mixed and filtered, then spray-dried with hot air at 160°C for 30 min, and stored at room temperature. For the acute toxicity test, 72.0 g/kg of QHGC extract was administered by gavage to male and female mice. Body weight, general observations, and autopsy results were recorded. No mortality or toxicity signs were observed during the studies. For the subacute toxicity test, 4.0, 8.0, or 16.0 g/kg/day of QHGC extract was administered to rats for 28 days. General observations and mortality, body weight, biochemical and hematological parameters, organ weight, and pathological morphology were analyzed. The acute and subacute toxicity studies did not show significant changes in body weight, general observations, hematology and biochemical parameters, organ weight, and liver, spleen, stomach, duodenum, testis, ovary, lung, heart, and kidney histopathological analyses. The consumption of QHGC aqueous extract can be considered safe within the conditions of this study. [ABSTRACT FROM AUTHOR]

Nicotinamide mononucleotide (NMN), a key precursory metabolite of NAD+, has been shown to elevate the cellular level of NAD+ and ameliorate various age-related diseases. Despite these progresses, systemic evaluation pertaining to the subacute toxicity of NMN remains to be determined. Here, we examine the subacute toxicity of NMN in mice and beagle dogs. Mice were gavaged with a saturated concentration of NMN solution at the maximum intragastric dose once or twice per day for 7 days. Dogs were gavaged twice per day for 14 days. In mice, NMN administrated once per day for 7 days is well tolerated with minimal deleterious effects. Upon higher dosage, we observe slightly increased level of alamine aminotransferase, while other biomarkers remain unchanged. Consistently, administration of NMN in beagle dogs only results in mild increases in creatinine and uric acid. Together, our study highlights the safety of NMN, providing a possible safe dose range for oral administration of NMN.

Background: Malaria is an infectious disease-causing mortality and morbidity in children and adults. Our study planned to measure the antimalarial activity of Combretum molle extract in vivo assays against Plasmodium berghei in Swiss albino mice. Methods: Plasmodium berghei was inoculated to healthy mice and methanolic crude extract and solvent fractions of C. molle at 100, 200, and 400mg/kg/day were administered. Percent parasitemia inhibition, percent change in weight, temperature, packed cell volume, and mean survival time were determined. Data were analyzed using one-way ANOVA followed by the post hoc Tukey HSD test with SPSS software version 24.0 and P < 0.05 considered as statistically significant. Results: Chemosuppresive effect exerted by the methanolic crude extract ranged between 27 and 68%, chloroform fraction 52.93– 67.73%, hexane fraction 23.61– 44.97%, and aqueous fraction 29.48– 51.13%. The curative effect of the crude extract was within the range of 25– 49%, chloroform fraction 42.78– 69.22%, and prophylactic effect of the crude extract was within the range of 51– 76.2%% and chloroform fraction 46.57– 71.96%. The utmost effect in all tests on chemosuppresive, curative, prophylactic, prevention of weight loss, temperature and packed cell volume, and an increase in mean survival time was observed at higher doses of the crude extract. Conclusion: From this study, it will be concluded that crude extract of C. molle leaves has been shown promising antimalarial activity. The findings of this study may support the normal use of leaf as a part of the plant for malaria treatment. [ABSTRACT FROM AUTHOR]

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The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Ping, Sun, Yang, Lu and Pei.)

The aim of this study was to evaluate the 28 days repeated dose oral toxicity or subacute oral toxicity study of hydroalcoholic extract of Helicteres isora (HAEHI) dried fruits in male and female experimental wistar rats. This toxicity study was carried out at 200mg/kg, 500mg/kg and 1000mg/kg of doses of hydroalcoholic extract of Helicteres isora dried fruits. During the study period of 28 days all the animals were observed weekly for changes in body weight, food consumption, water consumption, behavior changes, any sign of morbidity and mortality. After 28 days of study period, all the animals were humanly sacrificed by using cervical dislocation technique and were examined for changes in their relative organ weight, biochemical and hematological parameters and also observed for histopathological changes. The results of the present study indicated that there is increase in food consumption as well as elevated body weight at 1000mg/kg doses in both male and female wistar rats. The results of biochemical tests and hematological tests show significant changes in some parameters at higher dose of HAEHI. In the histopathology, animals treated with extract at 1000mg/kg body weight showed minimal tubular degeneration in kidney of both male and female wistar rats; however, liver, heart and lungs did not show any toxicity at any of the doses when compared with control group animals. From results, our study concludes that repeated administration of hydroalcoholic extract of H. isora dried fruits for 28 days increases the food consumption along with body weight and indicates its role as dietary supplement. The hydroalcoholic extract of Helicteres isora dried fruits was found to be safe in 28 days repeated dose toxicity study. While at higher doses it shows minor significant alteration in histopathology, biochemical and hematological parameters. [ABSTRACT FROM AUTHOR]

Background: Arishta technology is an age-old heritage and uses herbal decoctions to prepare self-generated alcoholic medicines. In Ayurveda, Arishta preparations are widely used as a remedy for metabolic disorders. However, their safety and influence on herb metabolism pathways were not yet explored. Aim: To study the subacute toxicity of a polyherbal Arishta formulation (coded as DB-07) in rats and to evaluate its potential for inhibition of the drug-metabolizing enzyme (Cytochrome P450 3A4). Methodology: Experimentally naive rats were treated with graded oral doses of DB-07 (10 and 20 mL/kg/day) for 28 days. During the course of the experiment, all the animals were closely observed for apparent behavioural abnormalities and mortalities. Tissue histology was performed to assess any sign of toxicity. In addition, in vitro CYP3A4 inhibition assay was performed to study the effect on drug metabolism pathways. Results: Animals did not show any change in body weight, organ toxicity and food consumption throughout the dosing period of 28 days. Pathophysiological, behavioural status and locomotor activity were not altered. DB-07 did not inhibit CYP3A4 enzyme and drug metabolism pathway in-vitro. Gallic acid and quercetin were identified as phytomarker from the formulation that may be responsible for its activity related safety issue. Conclusion: These results indicate that use of DB-07 may be safe with no sign of toxicity for up to 28 days in rats. Further, CYP3A4 inhibition assay indicated that DB-07 is less likely to have herb–drug interactions when concomitantly administered with CYP3A4 inhibitors or inducer. [ABSTRACT FROM AUTHOR]

Global dissemination of carbapenem resistant-Gram negative bacteria (CR-GNB) is supposed to be clinically alarming because it extremely delimits the treatment options against serious infections. 4-Chloromercuribenzoic acid (pCMB) is an efficient metallo-enzyme inhibitor, and quercetin is known for antioxidant, antiviral, anticancer, antimicrobial, and anti-inflammatory activities. These two compounds could be considered as potential candidates for the treatment of CR-GNB mediated infections. Hence, in this study, antibacterial activity of pCMB and quercetin was evaluated against CR-GNB through minimum inhibitory concentration (MIC) determination. Toxicity of pCMB and quercetin was evaluated by LC50 calculation through brine shrimp test (BST) and by investigating hematological, serum biochemical, and histopathological parameters in Swiss-albino mice. Moreover, aggressive–depressive–cognitive behavioral effects of pCMB and quercetin on murine model were evaluated. All the carbapenem resistant isolates (CR-GNB) exhibited MIC values in the range of 4–256 μg/ml, 16–256 μg/ml, and 64–1024 μg/ml for pCMB, quercetin, and meropenem, respectively. BST determined LC50 of pCMB and quercetin at 91.57 ± 0.35 mg/L and 448.45 ± 0.46 mg/L, respectively. Oral administration of low dose of pCMB and quercetin did not induce any significant changes in morphological, behavioral, hematological, serum biochemical, and histopathological parameters among Swiss-albino mice. But, a high dose of pCMB and quercetin exhibited slight toxicity. However, no death was reported for any dosage of pCMB and quercetin. Therefore, pCMB and quercetin might be considered for further investigations on alternative therapeutics to combat against CR-GNB. [ABSTRACT FROM AUTHOR]

Introduction: Camellia sinensis var. assamica (Assam tea or Cha-Miang [CM]) is widely accepted to be beneficial to health. The tea leaf is used to produce various fermented tea products such as black tea (China, India) and Miang (Thailand). Despite its medicinal properties, toxicological information regarding certain tea variety and its fermented Miang product, especially its long-term toxicity, is currently limited. This study aimed to evaluate the potential toxicity of the extract of fresh resh Cha-Miang leaves (CM) and its fermented Miang product (FCM) in both in vitro and in vivo models. Materials and Methods: Cytotoxic effect on cell viability of HepG2, HEK293, and EA.hy926 cell lines incubated with CM or FCM extract for 24 h and 48 h was investigated by the MTT assay. After that, 14-day repeat oral toxicity test was performed on Wistar rats. Results: No in vitro cytotoxic effect of CM and FCM extract was found in the tested cell types, at a dose up to 1000 μg/ml. For in vivo study, both CM and FCM extracts at a dose of 300 mg/kg/day did not produce any sign or symptom of toxicity; no mortality was observed. Furthermore, investigation of hematological parameters, blood chemistry, body weight, and organ weight in the treated rats revealed no significant difference compared with that of normal controls. Conclusion: The results suggested that crude extract of CM and FCM at the doses used in this study are safe, however, further evaluation of possible chronic toxicity is recommended. [ABSTRACT FROM AUTHOR]

Objectives: Vanillic acid (VA) is a flavoring agent, a phenolic acid, and an intermediary by-product formed during transformation of ferulic acid to vanillin. It has been investigated for diverse pharmacological actions and used in Chinese medicine for decades. However, there is no information in the literature about its mechanism of toxicity or safety with long-term use. The present study will not only supply information on its pharmacological profile but also encourage evidence-based pharmacotherapeutic use. Hence, we performed a subacute toxicity study. Materials and Methods: According to the Organisation for Economic Co-operation and Development Test Guideline 407 (2008), 3 groups of rats were formed consisting of 12 rats (6 male and 6 female) in each group. For the subacute toxicity, the dose was chosen after a limit test was conducted. VA (1000 mg/kg/day) was orally administered for 2 weeks to the treatment group, whereas the control group received an equivalent volume of the vehicle. To assess reversibility, VA (1000 mg/kg/day, p.o.) was administered to the satellite group for 2 weeks and animals were observed for an additional 2 weeks after treatment. The adverse signs, variation in body weight, and mortality were evaluated throughout the study period. On days 15 and 29, blood was collected to evaluate essential biochemical and hematological parameters. The animals were subsequently weighed and sacrificed. The weights of internal organs were recorded; gross necroscopy and histopathological studies were performed. Results: The hematological parameters of the satellite group increased and the serum sodium level decreased after the treatment. Satellite groups showed no other major change in biochemical parameters when compared to the control group. In addition, relative organ weights, gross necropsy examinations and histopathological structure of the internal organs showed no major alterations. Conclusion: VA showed no adverse effect on the process of leukopoiesis, erythropoiesis or on internal organs, as verified by hematological and biochemical evaluations, gross necropsy, and histopathological studies. The decrease in serum sodium is not considered as a major toxic effect. [ABSTRACT FROM AUTHOR]

Melodinus henryi is a good source of terpenoid indole alkaloids, and traditionally used as a folk medicine in the treatment of meningitis and fracture. In order to further exploit their potential uses, its anti-inflammatory and immunosuppressive activities, safety evaluations and chemical profiles have been illustrated. Compared to the crude methanol extract from M. henryi and its non-alkaloidal fraction, the total alkaloidal fraction (MHTA) had the strongest anti-inflammatory and immunosuppressive activities. In the acute oral toxicity assay, the half lethal dose (LD50) of MHTA was more than 2000 mg/kg. The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe, and might damage spleen, liver, kidney, and heart when the dose is higher than 1000 mg/kg. In addition, a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids. Thus, in regard with the potent side effects of MHTA, it should be used with caution in the development of phytomedicine. [ABSTRACT FROM AUTHOR]

The present study was carried out to evaluate oxidative stress mediated pathophysiological alterations in brain cerebral cortex and testes of rats exposed to cadmium chloride at 15, 50 and 100 ppm in drinking water for 28 days. The activity of SOD in brain of rats of all toxicity groups was non- significantly decreased. The SOD activity in testes was significantly decreased in animals exposed to 50 and 100 ppm level of cadmium. The catalase activity in brain cerebral cortex and testes was significantly decreased in dose dependent manner. The GSH levels in brain and testes tissue were increased at all tested levels of exposure of cadmium. The acetylcholinesterase activity in brain of rats exposed all levels of Cd were significantly decreased. Cadmium exposure at 100 ppm level significantly reduced the total epididymal sperm count. However, the epididymal sperm motility was significantly reduced in rats exposed to all tested levels of cadmium. The different levels of cadmium exposure produced pathological lesions in brain cerebral cortex and testes which were remarkable at 100 ppm level of exposure as compared to other levels of exposure in rats. In conclusion, cadmium exposure at 100 ppm for 28 days in rats produced marked alterations in both brain and testes through oxidative insult. [ABSTRACT FROM AUTHOR]

An ethanol extract complex of Descurainia sophia seeds and Peucedanum praeruptorum roots, called BP10A, has antitumor potential against colorectal cancer. In the present study, we evaluated the 28‐day oral toxicity and the genotoxicity of BP10A. The subacute toxicity test was done through oral administration to mice. ICR mice (n = 10) received daily oral BP10A doses of 0, 500, 1000 and 2000 mg/kg for 28 consecutive days. During administration, general clinical signs, food consumption, organ weights, and hematologic, biochemical and histopathological parameters in male and female mice were assessed. No significant adverse effects up to the highest dose (2000 mg/kg) were found. The genotoxicity was evaluated using a battery of tests, including an in vitro bacterial reverse mutation (Ames) test, an in vivo micronucleus test using bone marrow cells in ICR mice and a chromosomal aberration test using CHL/IU cells. BP10A did not show any genotoxic signs in the Ames (up to 5000 μg/plate), micronucleus (up to 5000 mg/kg) and the chromosomal aberration tests (550‐1750 μg/mL). Therefore, BP10A was considered safe based on the subacute toxicity and genotoxicity results, indicating that it is a useful pharmaceutical material with no adverse toxicity. An ethanol extract complex of Descurainia sophia and Peucedanum praeruptorum was evaluated toxicologically by subacute oral toxicity and genotoxicity studies. The genotoxicity was evaluated using a battery of tests including an in vitro bacterial reverse mutationtest, an in vivo micronucleus testusing bone marrow cells in ICR mice, and a chromosomal aberration test usingCHL cells. BP10A did not show significant adverse effects and genotoxic signs within the dose range used inthis study. [ABSTRACT FROM AUTHOR]

This study evaluated the biodistribution and organ oxidative effects of silver nanoparticles (AgNPs) coated with/without polyvinylpyrrolidone (PVP) (AgNP‐20 and AgNP‐PVP) in mice; these were administered by gavage at a dose of 10‐250 mg/kg body weight per day for 28 days. The results showed that both the AgNPs could induce subacute toxicity and oxidative damage to mice and were mainly accumulated in the liver and spleen and excreted by feces. AgNPs could be absorbed into blood and might cross the blood‐brain barrier, and be distributed extensively in mice. The malondialdehyde content in the liver, lungs and kidneys increased in both AgNP groups, while the content of glutathione decreased, and the activity of superoxide dismutase increased at first and then decreased along with the increased doses. Inflammatory pathological changes in the lung and liver at high dose of both AgNPs were consistent with increases in glutamate pyruvic transaminase, glutamate oxaloacetic transaminase and the total protein in serum detection. The Ag content was detected in organs, with the highest content in the liver, followed by spleen, while the Ag content in feces was about 500 times higher than that in urine. AgNP‐PVP could induce higher oxidative stress and subacute toxicity than AgNP‐20 at the same dose, which might be related to the higher concentrations and more Ag+ ions released in mice after AgNP‐PVP exposure. The data from this research provided information on toxicity and biodistribution of AgNPs following gavage administration in mice, and might shed light for future application of AgNPs in daily life. The biodistribution and organ oxidative effects of nanosilver with/without coating were evaluated by general behavior, body weight, organ coefficient, serum biochemistry, histopathology and Ag content detection following oral administration in mice for 28 days. It was found that the two Ag nanoparticles (NPs) could cause subacute toxicity and organ oxidative damage to mice, and were distributed extensively in the body of mice. The toxicity caused by 20 nm silver nanoparticles coated with polyvinylpyrrolidone (AgNPs‐PVP) was greater than that caused by silver nanoparticles without coating at 20 nm (AgNPs‐20). [ABSTRACT FROM AUTHOR]

Thymoquinone (TQ) is a naturally occurring quinone derivative and its metabolism may produce reactive oxygen species which in turn may lead to various adverse effects. Here, we discuss in vivo data concerning toxicological effects of TQ. Previous studies showed LD50 values of 250–794 mg/kg in rats and 300–2400 mg/kg in mice for oral TQ but 57 mg/kg in rats and 90.3–104 mg/kg in mice for intraperitoneal TQ. In subacute toxicity evaluations, NOAEL was about 10 mg/kg. Though TQ has been found as an almost safe chemical, detailed studies are required before introducing TQ as a therapeutic agent for human use. [ABSTRACT FROM AUTHOR]

Background: Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissuecultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. Results: No death or toxicity symptomswere observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. Conclusions: The water extract of tissue-cultured T. formosanumwas non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains. [ABSTRACT FROM AUTHOR]

Aim: Nalbuphine (NLB) is an approved opioid analgesic for the management of severe pain in wounds, battlefield injuries and is recommended to subsidize labour pain during childbirth. The study aims to develop an intranasal opioid formulation for faster pain relief. Secondly to avoid patient inconvenience and make it available for buddy care. In case of war, accident or any natural calamities the feasibility of giving drugs from the parenteral route is not feasible as it requires high skilled medic/paramedic staff. Materials and Methods: Different formulations were made using NLB as an Active Pharmaceutical Ingredient (API), prepared formulations (F1-F10) were characterized and evaluated for various parameters. The formulation F5 was optimized as it met the desired criteria. F5 was further studied for its efficacy in an established pain model using Eddy's hot plate method and pain scoring in animals. Pharmacodynamics study was conducted in Sprague dawley rats which were further verified by gamma scintigraphy using 99mTc-pertechnetate labelled NLB showing significant and rapid deposition in the brain tissue. Results: NLB nasal formulation was optimized successfully; at pH 6.4±0.10 and viscosity 2.5±0.13 (cps). Osmolarity and percent drug release of optimized nasal drop at 240 min was found to be 288±18 milliosmol/litre and 96.98±3.1% respectively. Gamma scintigraphy study results revealed that the formulation (F5) was able to deliver NLB to the brain within 10 mins of administration and remained localized up to 240 min. Pre-clinical subacute toxicity profiling of optimized formulation was done in Sprague dawley rats at 3X dose. Conclusion: Data obtained from the study indicate that the developed NLB nasal formulation has better efficacy for pain management than conventional I.M injection. [ABSTRACT FROM AUTHOR]

Fish processing produces a lot of by‐products highly containing large amount of proteins which mainly consist of collagen, implying great potential value for application as nutraceutical ingredients. In present study, two kinds of sharks, Chiloscyllium plagiosum and Mustelus griseus, were used as raw material to gain three kinds of "compound peptides" (CPs) by enzymolysis, FCP (CPs from the flesh of C. plagiosum), SCP (CPs from the skin of C. plagiosum), and SMG (CPs from the skin of M. griseus). According to a series of constituent analysis, the molecule weights of FCP, SCP, and SMG were under 800 Da; amino acids composition analysis of FCP, SCP, and SMG showed that there were high glycine, proline, and hydroxyproline and low cysteine contents in SCP and SMG, which is the characteristic of collagen peptides; their total protein contents were 87.500%, 91.875%, and 95.625%, respectively; and heavy metal contents of CPs were all beneath national standards. After three kinds of CPs were administrated intragastrically to C57BL/6 mice at a total dosage of 15 g/kg, bone‐strengthening effects of SCP and SMG were manifested by osteoblasts activity promotion, bone mineral density (BMD) increase, and marrow adipocyte number decrease, yet nonsignificant effects were shown in FCP group. No index showed toxicity of SCP and SMG in subacute toxicology trial, indicating their safety as functional foods. Herein, industrial application foundation of the skins from these two sharks was explored but more efforts should subsequently be implemented for further exploitation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low‐sodium sausages were manufactured using sodium substitution and biopolymer encapsulation. A diet comprising 10% treatment sausages (six treatment groups: C (100% NaCl), T1 (55% sodium substitute + 45% saltwort salt), T2 (55% sodium substitute + 45% saltwort salt with chitosan), T3 (55% sodium substitute + 45% saltwort salt with cellulose), T4 (55% sodium substitute + 45% saltwort salt with dextrin), and T5 (55% sodium substitute + 45% saltwort salt with pectin)) was added to a 90% commercial mouse diet for 4 weeks. RESULTS: Subacute toxicity, hematology, liver function, and organ weight tests in low‐sodium sausage groups showed results similar to those of the control group, and all toxicity test levels were within normal ranges. CONCLUSIONS: All low‐sodium sausage types tested are suggested to be safe in terms of subacute toxicity. Moreover, low‐sodium sausages can be manufactured by biopolymer encapsulation of saltwort using pectin, chitosan, cellulose, and dextrin without toxicity. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Hematotoxicity study of butanol fraction of Cassytha filiformis L. on white male mice has been performed. A total of 12 white male mice were used, and they were divided into four groups. Each group consists of 3 mice. These animals were treated with Cassytha filiformis L. butanolic fraction at several doses of 2.5, 5, and 10 mg/kg for seven days. Hemoglobin value, erythrocytes, platelets, leukocytes, monocytes, lymphocytes, eosinophils, neutrophils, and basophils counts were measured at the 1st, 3rd, and 7th day of treatment. The data of this study were analyzed using two-way ANOVA, followed by Duncan's multiple region tests. The results showed that the doses of butanol fraction did not affect hemoglobin value, erythrocytes, leukocytes, and neutrophils (p >0.1), but it significantly reduced platelet, monocyte, lymphocyte count, and increases eosinophils (p <0.01) counts within their normal limits. There is no influence on the duration of administration and the interaction of dosage, and also the duration of use of the parameters above. This result implies that the Cassytha filiformis butanol fraction at doses of 2.5-10 mg/kg does not affect hematology parameters if it were used for seven days. [ABSTRACT FROM AUTHOR]

Background: Naturally ripened fruits play a vital role in human nutrition. Under certain conditions, synthetic chemicals like calcium carbide (CaC2) and ethylene glycol (EG) are being freely used illegally in India and other countries for fruit ripening without serious concern on its toxic effects. This preclinical study evaluated the toxicity on different organs after the exposure of industrial-grade CaC2 and EG to the rats. Methods: Acute toxicity was induced by the oral administration of a single dose of chemicals to the rats, and their morbidity and mortality were monitored. For subacute study, different organs of animals were analyzed biochemically and histologically after the exposure of low doses of chemicals for 30 days. Results: At an acute dose of 5 mg/kg body weight of CaC2, 85% of the animals were found dead within 14 days; however, no mortality was observed following EG administration. At subacute doses, RBC and hemoglobin levels were found to be declined (p < 0.01), whereas total WBC and platelet counts, especially lymphocytes, were elevated remarkably (p < 0.01). Total protein, albumin, and urea were also found to be increased (p < 0.01). Histopathological observations support the toxicity in rats at higher doses of CaC2 and EG. Conclusions: The study revealed that the artificial fruit-ripening agents like CaC2 and EG cause toxic effects on the internal organs of rats. The subsequent inflammatory response might have weakened the immune system. This in turn suggests the requisite for urgent measures to regulate the use of harmful synthetic agents in fruit ripening. [ABSTRACT FROM AUTHOR]

Herbal products from Paullinia pinnata Linn are widely used in African folk medicine to treat several infectious diseases. Although the extracts from this plant has been shown to possess antimicrobial potential, their activity in infectious diarrhea is less reported. Diarrhea was induced by oral administration of 1.2 × 109 CFU/mL of Shigella flexneri to the rats. The infected rats were treated for 5 days with the doses of 111.42, 222.84, and 445.68 mg/kg of P pinnata. The level of biochemical parameters was assessed and histology of organs examined by 14 days subacute toxicity. S flexneri stool load was considerably reduced after 4 days of treatment with the dose of 445.68 mg/kg, 5 days at the dose of 222.84 mg/kg for the extract, and 2 days with ciprofloxacin. The dose of 111.42 mg/kg appeared efficient after 5 days of treatment. The creatinine level increased at the dose of 445.68 mg/kg in both male and female rats and decrease at the dose of 222.84 mg/mL in female rats while an increase was noted in the male rats. Liver and kidney histology were modified at the dose of 445.68 mg/kg while no change was observed at the doses of 111.42 and 222.84 mg/kg. P pinnata leaf extract is efficient against infectious diarrhea at 111.42 mg/kg without side effect. [ABSTRACT FROM AUTHOR]

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD50) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30–80 nm. The LD50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg. [ABSTRACT FROM AUTHOR]