Organ Weights Research Articles

Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE-/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE-/- mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

Toxicological evaluation of Carthamus lanatus L (Carthame laineux) hydro-alcoholic extract in Wistar rats: acute oral toxic effects

Background: Despite the well-known phytotherapeutic properties of Carthamus lanatus L in traditional medicine, there is little evidence on its toxicity profile in hematological and biochemical parameters. Objective: This study was intended to evaluate the acute toxicity effect of Carthamus lanatus L. Methods: The toxicological impact of a hydroalcholic extract of Carthamus lanatus (HAECL) at 200, 400, and 800 mg/kg body weight on hematological indices in rats was assessed gradually at 24 hours after 1, 10, and 14 days. Results: We observed no significant difference in the consumption of food, body weight, or relative organ weights. Hematological and biochemical parameters revealed the non-adverse effects of prolonged oral consumption of Carthamus lanatus except for a slight increase but no significant increase in ASAT and ALAT and a no significant decrease in the percentage of basophils. Conclusions: These data imply that the extract has a non-hematotoxic potential. Overall, the impact of carthamus lanatus extract in this study shows that it is unlikely to be hematotoxic and might be a promising candidate in the treatment of coronary heart disease if taken at the levels tested.

Cold-Pressed Aristotelia chilensis (Mol.) Stuntz Seed Oil Prevents Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat-Diet-Induced Obesity Murine Model

This study evaluated the effects of cold-pressed maqui (Aristotelia chilensis (Mol.) Stuntz) seed oil (MO) on liver metabolism and biochemical markers in a high-fat diet (HFD) murine model. In it, the fatty acid profile, tocopherol and tocotrienol contents, and antioxidant capacity of MO were analyzed. Male C57BL/6 mice were divided into four groups (i.e., a, b, c, and d groups) and supplemented for 12 weeks according to the following distribution: (a) control diet (CD)-sunflower oil (SO), (b) CD+MO, (c) HFD+SO, and (d) HFD+MO. Total body and organ weights, serum markers, and liver fat infiltration were assessed. MO contained 32.31% oleic acid, 46.41% linoleic acid, and 10.83% α-linolenic acid; additionally, α- and γ-tocopherol levels were 339.09 ± 5.15 and 135.52 ± 38.03 mg/kg, respectively, while β-, δ-tocopherol, and α-tocotrienol were present in trace amounts and the antioxidant capacity measured was 6.66 ± 0.19 μmol Trolox equivalent/g. MO supplementation significantly reduced the visceral fat (0.76 ± 0.06 g vs. 1.32 ± 0.04 g) and GPT (glutamate pyruvate transaminase) levels (71.8 ± 5.0 vs. 35.2 ± 2.6 U/L), and the liver fat infiltration score (6 vs. 3) in the HFD+MO group compared to HFD+SO. It is suggested that MO may effectively prevent fatty liver disease, warranting further research on its potential benefits for human health.

Preclinical delayed toxicity studies of BCMA CAR T-cell injection in B-NDG mice with multiple myeloma

PurposeBased on the efficacy data from the previous study of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell injection, we further examined the delayed toxicity for 8 weeks after a single dose of BCMA CAR T-cell injection to observe possible toxic reactions.MethodsB-NDG mice transplanted with multiple myeloma (MM) cells were given a single dose of BCMA CAR T-cell injection at two dosages or human normal T cells and then subjected to examinations including clinical signs, weight and food intake measurements, haematology, blood biochemical analysis, cytokine assay, T-lymphocyte subpopulation quantification and histopathology on days 28 and 56 after dosing. In addition, quantitative polymerase chain reaction (qPCR) was used to quantify DNA fragments in different tissues to assess the tissue distribution of CAR and provide a basis for its preclinical safety evaluation and clinical dosing.ResultsIn the delayed toxicity study, no mortality or significant toxic effects such as reductions in food intake, body weight, relevant biochemical parameters and target organ weights were observed in the BCMA CAR T-cell-treated groups. Compared to the model group, restorative changes in clinical signs and clinicopathology indicating therapeutic effects were seen in the BCMA CAR T-cell-treated groups. Human-derived cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-12, IL-10, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) could be detected in all cancer cell–bearing mice by cytokine level measurement. IFN-γ levels showed a geometric increase due to the graft versus host disease (GVHD) response induced in the mice, while the levels of the other cytokines did not show significant changes. Histopathological examination indicated that the BCMA CAR T-cell treatment groups showed mixed cellular infiltration of human-derived T cells, cancer cells, and inflammatory cells in several target organs including the liver, spleen, lung, and kidney, and some of them showed mild tissue damage, but the number of the animals and the severity of damage were significantly less than those of the T-cell control group as well as the model group. The results of the tissue distribution study showed that BCMA CAR T cells were mainly concentrated in the kidney, lung, bone marrow and the related immune organs/tissues, and the distribution of BCMA CAR T cells was highly consistent with that of MM cells, suggesting that BCMA CAR T cells could follow the cancer cells during metastatic targeting of the tissues.ConclusionsThe present study demonstrated a low toxicity of BCMA CAR T-cell injection, with manageable side effects and good anticancer activity and without observable adverse effects. This study provides data to support future clinical studies of BCMA CAR T-cell injection for MM.

The Effect of Ketoconazole and Quinestrol Combination on Reproductive Physiology in Male Mice

This study investigates whether ketoconazole, a CYP3A4 inhibitor, can enhance the suppressive effects of quinestrol on reproductive capacity, potentially allowing for a reduced quinestrol dosage while maintaining its efficacy. A total of 104 healthy adult male mice were divided into two groups, assessed at 10 and 30 days. Within each group, six treatment categories were tested: the control (CK), quinestrol alone (Q1, Q5), and quinestrol combined with varying doses of ketoconazole (Q1 + K0.4, Q1 + K2, Q5 + K0.4). The key parameters measured included internal and reproductive organ weights, sperm density, sperm motility, sperm abnormalities, and CYP3A4 enzyme content in intestinal and liver tissues. After 10 days, the combination of a low dose of quinestrol with ketoconazole (Q1 + K0.4) showed the most significant pronounced effects in reducing reproductive potential, with notable reductions in epididymal weight, sperm density, sperm abnormality rate and vitality, serum hormone levels, and CYP3A4 content in the small intestine and liver. Although some reproductive parameters returned to near-baseline levels after 30 days, the Q1 + K0.4 regimen continued to exhibit reduced seminal vesicle weight and testosterone levels. Importantly, the combination did not significantly increase CYP3A4 enzyme content, indicating effective metabolic inhibition. The combination of quinestrol and ketoconazole, especially the Q1 + K0.4 regimen, demonstrated the most noticeable impact on reducing reproductive capacity. This regimen significantly reduced key reproductive parameters and showed strong metabolic inhibition, suggesting that ketoconazole substantially enhances the efficacy of quinestrol in fertility control.

TUDY OF CHRONIC TOXICITY OF AN IMPROVED A-SILICONE IMPRESSION MATERIAL PRODUCED IN UKRAINE

The objective of this study is to evaluate the potential toxic effects of an improved A-silicone impression material with decorative properties on the organs and mucous membranes of laboratory animals. Materials and Methods The experiment was conducted on white laboratory rats aged 9 months and weighing 230–285 g. Findings indicate that prolonged contact (30 days) with the material does not result in significant changes in the function of major organ systems in these laboratory rats. Results. A single exposure of laboratory rats to A-silicone impression material with disinfectant properties did not cause significant changes in the physiological state of the animals. Weights of internal organs, including the liver, spleen, heart, and adrenal glands, remained within normal limits, indicating that the material had no toxic effects. The analysis of the peripheral blood composition did not reveal any abnormalities in the number of red blood cells, leukocytes, hemoglobin and other cellular components. The functional state of the liver and kidneys, including the activity of the enzymes AlаT and AсаT, levels of total protein, albumin, creatinine and urea, remained stable and did not change under the influence of the material. There was also no effect on carbohydrate metabolism. No abnormalities in protein synthesis and nitrogen excretion functions were detected, which confirms the safety of the material during the 30-day observation. Conclusion. It was established that this material in the tested dose does not affect the enzyme-synthetic function of the liver and does not exhibit cytolytic effects. The material was found to have no toxic impact on liver function with prolonged use, nor does it cause statistically significant deviations in the measured indicators between the control and experimental groups. The absence of sugar, ketones, and protein in the urine indicates no adverse effect on the renal nitrogen-excreting and saluretic functions, as well as on the vital organs of the rats.

DDEL-17. INTRA-TUMORAL CONVECTION ENHANCED DELIVERY OF DEXAMETHASONE REDUCES INFLAMMATORY SIGNATURES AND EXTENDS SURVIVAL IN GBM MODEL

Abstract Dexamethasone is the most widely utilized drug for glioblastoma (GBM). However, systemic delivery of dexamethasone in GBM patients is associated with significant side effects and increasing doses with worse survival. Convection-enhanced delivery (CED) can deliver high doses of immunotherapy directly into the tumor microenvironment (TME) while avoiding systemic toxicity. Here, we report that high doses of dexamethasone can be delivered locally by CED without side effects and increase survival in a GBM model along with reduced inflammatory myeloid signatures. We investigated CED of dexamethasone treatment on survival(n=40), adverse side effects, and the immunological TME through peripheral analyses, liquid chromatography–mass spectrometry, and histology in a preclinical syngeneic mouse model. Additionally, we assessed the transcriptional responses of human GBM slices and stem-cell-derived human microglia after steroid treatment through bulk and single-cell RNA sequencing. We found that 7-day treatment with CED of dexamethasone produced a significant survival advantage in glioma-bearing mice compared to non-treated control(p=0.03). Systemic dexamethasone achieved low levels of drug in the TME and caused dysregulated blood glucose, blood counts, and peripheral organ weights, while high CED doses avoided these side effects(p< 0.05 each). Steroid treatment of acute GBM slices and lipopolysaccharide-activated microglia in-vitro both reversed inflammatory myeloid signatures associated with poor survival and recurrence on RNA sequencing analyses. We demonstrate the preclinical efficacy of delivering high local doses of dexamethasone in a GBM model through CED and observed prolonged survival along with reduced adverse inflammatory myeloid signatures. No side effects were demonstrated after chronic CED treatment of dexamethasone while systemic delivery achieved poor tumor penetration and caused known hematologic and metabolic side effects supporting the potential to optimize the clinical use of this therapy. CED of dexamethasone provides us a new treatment paradigm to locally control inflammatory signatures in the glioma TME in a controlled fashion.

Responses in organs, sperm, steroid hormones and CYP450 enzyme in male mice treated by quinestrol only or in conjunction with clarithromycin

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Optimising growth performance, nutrients digestibility, immunity and gut health in broilers through ginger-derived phyto-protease enzyme (zingibain) supplementation

This study investigated the impact of ginger-derived phyto-protease enzyme on growth performance, immunity, gut health and nutrient digestibility in broilers. A total of 360 day-old broiler chickens were randomly assigned to four treatments with six replicates each: a control group (T1) and groups supplemented with 50 g/ton (T2), 100 g/ton (T3) and 150 g/ton (T4) of the enzyme. Over a 35-day period, birds were provided with free access to feed and water under controlled conditions. The highest feed intake was observed in T3 during the second week, while T4 showed the lowest intake overall. Body weight gain was significantly highest in T4, demonstrating enhanced growth performance. Feed conversion ratio (FCR) was lowest in T4, indicating improved feed efficiency. Carcase quality analysis revealed higher dressing percentages and organ weights (bursa, spleen and thymus) in T4 compared to the control. Gut pH levels were significantly lower in T3 and T4 across different segments of the gastrointestinal tract, enhancing nutrient absorption. Antibody titres against Newcastle disease virus were significantly higher in T4 on days 21 and 35, indicating improved immunity. Histomorphological analysis of the intestines showed increased villus height and width in T4, with reduced crypt depth, further supporting enhanced nutrient absorption. These findings suggest that the highest inclusion rate of ginger-derived phyto-protease enzyme (150 g/ton) optimally enhances growth performance, immunity, gut health and nutrient digestibility in broilers. This study highlights the potential benefits of incorporating ginger-derived phyto-protease in poultry diets to improve overall health and performance.

The Effects of Shrimp Waste Added to Broiler Diets on Growth Performance, Slaughter and Carcass Characteristics, Intestinal Morphology, Bone Traits, and Fatty Acids in the Meat.

Recycling animal waste is crucial for the circular economy, promoting environmental and sustainability. This study aimed to assess the impact of shrimp waste added to broiler diets on growth performance, slaughter and carcass characteristics, intestinal morphology, bone traits, and fatty acids in the meat. In the study, 315 ROSS-308 male broiler chicks were utilised as the animal subjects. The experiment consisted of five groups based on the timing and amount of shrimp (Penaeus vannamei) waste addition to their diet (Control [C], 1% added the first 11 days [1% FED], 1% added during fattening [1% DF], 2% added during the first 11 days [2% FED], 2% added during fattening [2% DF]). The differences in body weight, body weight gain, total feed intake and total feed conversion ratio, carcass parameters, relative internal organ weights, and fatty acids of thigh and breast meat among the groups were found to be statistically insignificant (p > 0.05). The addition of shrimp waste to the diet only significantly affected the VH/CD ratio in the jejunum, with the C group showing a lower ratio (p < 0.05). Adding shrimp waste to the diet only affected the seedor index of the femur among the characteristics of the leg bones, and an interaction between the period and the group was observed for this trait (p < 0.05). According to the results, up to 2% shrimp waste can be added to the diet without adversely affecting broiler performance, carcass quality, villus and bone properties, and fatty acid composition. The use of shrimp waste in feed can benefit the broiler industry and protect to environment.

Efficacy and safety assessment of probiotic Bacillus coagulans (Heyndrickxia coagulans) BCP92 for treatment of diarrhea.

Probiotics offer a potentially new therapeutic approach for the treatment of diarrhea. This study aimed to determine the anti-diarrheal activity of Bacillus coagulans BCP92 (MTCC 25460) and its safety assessment (acute and sub-acute toxicity studies) in animal models and cell lines. The antidiarrheal activity was studied in mice using a castor oil-induced diarrhea model. In the acute toxicity study, the rats were orally fed 2000 mg/kg (4 × 1011 CFU/g) of B. coagulans BCP92 (MTCC 25460) as a single dose, and for sub-acute toxicity study rats received 250, 500, and 1,000 mg/kg/day for 28 days. At the end of the treatment, body weight, organ weight, food intake, biochemical parameters, hematological parameters, and histopathology were studied. B. coagulans BCP92 is effective against diarrhea by reducing the onset of diarrhea (latency), frequency of defecation, total fecal weight, and percentage of defecation. In-vitro MTT assay was performed on Vero cell lines. In-vitro MTT assay showed a cytoprotective effect. In acute toxicity study, 2000 mg/kg dose did not cause any alteration in clinical signs, morbidity, or mortality. The findings of the subacute toxicity study showed no alterations in physical appearance and behavioral patterns. Moreover, no significant variations were found in organ weights and hematological and biochemical parameters of the treated groups in the control group. Furthermore, no visible histological changes were observed in the heart, lung, liver, and kidney of the high-dose treatment groups. Thus, the results of the present study conclude that B. coagulans BCP92 is safe for human use in the treatment of diarrhea.

The novel lipid emulsion Vegaven is well tolerated and elicits distinct biological actions compared with a mixed-oil lipid emulsion containing fish oil:a parenteral nutrition trial in piglets

BackgroundVegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 fatty acids, which elicits liver protection via interleukin-10 (IL10) in the murine model of PN. ObjectiveIn a preclinical model of PN in neonatal piglets, Vegaven was tested for efficacy and safety and compared with a mixed-oil lipid emulsion containing fish-oil (SMOFlipid). Methods4-5-day-old male piglets were randomly allocated to isocaloric isonitrogenous PN for 14 days that varied only by the type of lipid emulsion (Vegaven, N=8; SMOFlipid, N=8). Hepatic IL10 tissue concentration served as primary outcome. Secondary outcomes were organ weights, bile flow, blood analyses, plasma insulin and glucagon concentrations, insulin signaling, proinflammatory cytokines, tissue lipopolysaccharide concentrations, and fatty acid composition of phospholipid fractions in plasma, liver, and brain. ResultsTotal weight gain on trial, organ weights, and bile flow were similar between the Vegaven and the SMOFlipid group. Vegaven elicited higher hepatic IL10 (Δ=148 pg/mg protein, p<0.001) and insulin receptor substrate-2 levels (Δ=0.08 O.D., p=0.012). Plasma insulin concentrations (Δ=1.46 mU/L, p=0.003) and fructosamine (glycated albumin, Δ=12.4 μmol/g protein, p=0.003) were increased in SMOFlipid as compared with Vegaven group, indicating insulin resistance. Higher hepatic injury markers were observed more frequently in the SMOFlipid group compared with the Vegaven group. Lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 were increased in pancreatic and brain tissues of SMOFlipid- vs Vegaven-treated piglets. Insulin signaling was reduced in the brains of SMOFlipid-treated piglets. Vegaven and SMOFlipid elicited distinct fatty acid profiles in the phospholipid fractions of the rapidly growing brains, but showed similar accretion of docosahexaenoic acid and arachidonic acid after two weeks of PN. ConclusionsVegaven was well tolerated in this piglet model of PN and demonstrated distinct biological actions compared with SMOFlipid, namely lower liver, pancreas, and brain inflammation, enhanced insulin signaling, and improved whole-body glucose control.

Interplay Between Western Diet and Mammary Cancer: Data from a Chemically-induced Model in Wistar Rats.

This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development. Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors. No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group. WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated.

Toxicological analysis and anti-inflammatory and antioxidant evaluations of extract, fractions and secoxyloganin obtained from Guettarda viburnoides Cham. & Schltdl. in mice

Ethnopharmacological relevanceGuettarda viburnoides, "veludinho do campo," is traditionally used for the treatment of pain and inflammatory conditions in humans; however, only one scientific study has reported this effect in an ear inflammatory model. Therefore, it is necessary to explore other in vivo models and the chemical composition of this medicinal plant. Aim of the studyA chemical investigation of methanolic extract of G. viburnoides (MEGV) (leaves) led to the isolation of secoxyloganin (GV-1). In addition, the preclinical safety of MEGV (in acute and subacute toxicological models, gavage = p.o.), antioxidants of MEGV, ethyl acetate (EAFGV) and hydromethanolic (HMFGV) fractions were tested using free radical scavenging and lipid peroxidation methodologies, and the anti-inflammatory effects of MEGV, HMFGV and GV-1 (p.o.) were evaluated on carrageenan and complete Freund's adjuvant (CFA) models of inflammation in mice. Materials and MethodsMEGV was obtained from air-dried leaves by maceration with methanol at room temperature. MEGV was then purified by liquid-liquid partitioning, to obtain the EAFGV and HMFGV fractions. Purification of HMFGV afforded GV-1. The quantification of total phenols, flavonoids, flavonols, and condensed tannins was subsequently performed for MEGV. The antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and oxidation of β-carotene were evaluated in MEGV and its fractions. The anti-inflammatory activity of MEGV (3, 30, and 100 mg/kg, p.o.) was assayed in carrageenan-induced models, followed by assessments of MEGV (100 mg/kg, p.o.), HMFGV (3 and 30 mg/kg, p.o.) and GV-1 (3 mg/kg, p.o.) in CFA- induced models in mice (including paw oedema, mechanical allodynia and cold sensitivity). Acute (14 days of MEGV, 2000 mg/kg, p.o.) and subacute (28 days, MEGV 30, 100, and 300 mg/kg, p.o.) toxicity was assessed in female Swiss mice. ResultsThe major compound was secoxyloganin (GV-1). The oral acute toxicity test of MEGV revealed no evidence of toxicity, indicating low toxicity according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the subacute toxicity group, no clinical signs of toxicity or changes in body weight, water consumption, food consumption, or organ weight or morphology were observed after 28 days of gavage with MEGV (30, 100, and 300 mg/kg) compared with those in the control group. MEGV, EAFGV, and HMFGV showed significant free-radical scavenging and lipid peroxidation activities, with IC50 values ≤ 26.38 ± 4.56 μg/mL. In in vivo anti-inflammatory assays, MEGV (3, 30 and 100 mg/kg) reduced carrageenan-induced oedema (2 and 4 h) and hyperalgesia (3 and 4 h). In the CFA model, MEGV (100 mg/kg), HMFGV (30 mg/kg) and GV-1 (3 mg/kg) reduced inflammation (at 3, 4 and 24 h) in all parameters (oedema, mechanical allodynia and cold sensitivity). ConclusionThis study revealed that G. viburnoides has antioxidant and anti-inflammatory properties, and no toxicity was detected after acute or subacute gavage with MEGV, validating its traditional use in the treatment of inflammatory conditions.

Evaluation of the Efficacy of Diosmin and Chrysin against Tau-fluvalinate Exposure in Rats

Tau-fluvalinate is a type 2 pyrethroid insecticide. Diosmin and chrysin are flavonoids with antioxidant and anti-apoptotic effects. Role of diosmin and chrysin against infavorable toxic effects caused by tau-fluvalinate and the underlying mechanisms of these effects were investigated. A total of 6 groups were formed and diosmin, chrysin, tau-fluvalinate, tau-fluvalinate+diosmin and tau-fluvalinate+chrysin were administered orally to rats at a dose of 20 mg/kg.bw from each, once a day for 21 days, respectively. Tau-fluvalinate elevated MDA and NO levels while diminishing the activities of antioxidant enzymes (SOD, CAT, GSH-Px, GR, GST, G6PD) and GSH levels in the majority of the analyzed blood and tissues, statistically significant. Serum triglyceride, cholesterol, total protein and albumin levels as well as LDH and PChE activities decreased. Conversely, serum creatinine, AST, ALT and ALP levels/activities increased. Elevated protein levels of caspase 3, caspase 9, p53 and Bax and decreased protein levels of Bcl-2 were observed in the liver. There were negative changes in body/some organ weights. Diosmin and chrysin administration resulted in a marked recovery in tau-fluvalinate-induced toxic effects, but this improvement was not complete. These flavonoids may be considered as promising potential therapeutic options to alleviate the adverse effects associated with tau-fluvalinate intoxication.

Cafeteria diet and caloric restriction affect metabolic but not behavioral characteristics in male Wistar rats

This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square field™ (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (p < 0.001) and increased adipose tissue weight in comparison to the control (p < 0.001) and restricted groups (p < 0.001). Glucose was significantly increased (p < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (p < 0.01; p < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (p < 0.01) and restricted (p < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (p < 0.001; p < 0.05) and restricted (p < 0.001; p < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development.

Acute and sub-acute toxicity of ethanol leaf extract from Acrostichum aureum in rats

Acrostichum aureum L. (A.aureum) is a medicinal plant that has anti-cancer, anti-inflammatory, and anti-bacterial activities and has been widely used traditionally in the treatment of many diseases. However, there is a dearth of information on the plant's safety. The present investigation was carried out to evaluate the acute and sub-acute toxicity of ethanol leaf extract of A. aureum (ELAA) in female Sprague Dawley (SD) rats. Oral acute toxicity was studied in female SD rats administered a single dose of 5000 mg kg-1 body weight ELAA. The sub-acute toxicity evaluation was also conducted orally with 100, 200, 500, and 750 mg kg-1 body weight of ELAA for 28 days in female SD rats. The impact of sub-acute treatment on body weight, gross histology, relative organ weight, urinalysis, hematology, plasma biochemistry, and histopathology was assessed following treatment. The ELAA did not cause death or signs of toxicity after acute treatment. Similarly, all the parameters evaluated during acute and sub-acute administration of ELAA did not significantly differ from the control. Therefore, the median lethal dose (LD50) of the ethanol extract of Acrostichum aureum is greater than 5000 mg kg-1 body weight. Its oral sub-acute administration is also non-toxic and safe at the tested doses.

Phytochemical and toxicological evaluation of aqueous leaf extract of Premna integrifolia L. in male balb/c mice.

BackgroundPhytoconstituents present in plants provide a natural and comprehensive method for combating oxidative stress and various ailments. Safety evaluation of these herbal medications is necessary, so acute and sub-acute toxicity of plant leaf extract Premna integrifolia has been performed to standardize its dose regarding its therapeutic application in male fertility. PurposeToxicological evaluation Aqueous leaf extract of Premna integrifolia (ALEPI), a known herbal medicine, for its utilization in male fertility enhancement use. Study design and methodsTo assess the safety and pharmacological potential of the ALEPI, acute and subacute toxicity studies were carried out in compliance with the OECD guidelines No. 425 and 407, respectively. Identification of pharmacologically active compounds in ALEPI was performed using UHPLC-HRMS analysis. In vitro,estimation of Polyphenol Content, Total Flavonoid Content, saponins and Antioxidant Properties of ALEPI was performed. The oral acute toxicity of the ALEPI was conducted using male mice. The study involved administering single doses of ALEPI at 300, 2000, and 5000 mg/kg b.wt., followed by a fourteen-day observation period to monitor any signs of toxicity or adverse effects. In the oral subacute toxicity study, mice received daily oral gavage of the ALEPI at doses of 400, 800, and 1000 mg/kg b.wt. for twenty-eight days. The parameters studied included total reactive oxygen species (ROS) production, apoptosis, cell viability percentage, and cellular morphology. ResultsThe UHPLC-HRMS analysis of the ALEPI reveals the presence of various bioactive compounds with significant antioxidant, anti-inflammatory, and anticancer properties. The acute and subacute toxicity studies of the ALEPI provided a comprehensive evaluation of its safety profile. Both studies demonstrated no mortality and only minor alterations in relative organ weights, hematology, and serum biochemistry, suggesting a low toxicity profile. Additionally, the normal histoarchitecture of vital organs indicates the absence of significant morphological changes. Significant reduction in total ROS, necrosis percentage, and apoptosis in testicular tissue compared to the control group highlights the antioxidant properties of the extract. ConclusionBased on the findings from both the acute and subacute toxicity studies, it is evident that the ALEPI does not actuate adverse effects of toxicological significance at the tested doses and hence can be used at appropriate concentrations in therapeutic application.

Aflatoxin B1-associated oxidative stress along with toxicopathological and immunological alterations is efficiently counteracted by dietary supplementation of distillery yeast sludge in broilers.

Aflatoxin B1 (AFB1) is among the most potent genotoxic and carcinogenic mycotoxins and is a major source of distress for the growing poultry sector. On the other hand, distillery yeast sludge or distillery sludge (DS) is a byproduct of molasses-based industries. It is often treated as a waste despite containing abundant nutrients particularly protein, basic amino acids, and vitamins along with other macro and micronutrients. This study was designed to investigate the oxidative stress and immunological alterations induced by AFB1 and their amelioration by dietary supplementation with DS. For this purpose, 360 newly hatched broiler chicks were randomly divided into twelve groups (30 birds each) and fed different combinations of AFB1 (100, 200, or 600µg/kg) and DS (5 or 10g/kg) for 42days. The parameters under consideration were body weight, feed conversion ratio (FCR), relative organ weights, histopathological examination of different visceral organs, total antioxidant capacity, antibody response to intravenous injection of sheep red blood cells, in situ lymphoproliferative response to phytohemagglutinin-P, and phagocytic potential through a carbon clearance assay system. The results of this study established that DS supplementation ameliorated AFB1-associated oxidative stress and ameliorated toxicopathological and immunological anomalies in groups given AFB1 at 100µg/kg and 200µg/kg; however, little to no relief was observed in birds fed AFB1 at 600µg/kg. The determination of the actual ratio of the AFB1 to the DS for substantiating the ameliorating effects requires further investigation.

Bacillus licheniformis as a protective agent in broiler chicken concurrently exposed to mycotoxins and necrotic enteritis: Toxicopathological and hematobiochemical perspectives.

Mycotoxins negatively impact intestinal cell viability, leading to the depletion of beneficial bacteria and rendering birds susceptible to intestinal infections such as necrotic enteritis (NE). Furthermore, they impair the effective digestion and absorption of nutrients. This study aimed to evaluate the effects of Bacillus licheniformis supplementation on broiler birds exposed to mycotoxins and subsequent necrotic enteritis infection. A total of 280 one-day-old broiler chicks were divided into eight groups and subjected to B. licheniformis supplementation (1 x 106 CFU/kg of feed) and mycotoxin exposure (aflatoxin and ochratoxin A, each at 150 ppb). Clostridium perfringens (3 x 1010 CFU/ml) was later administered to induce necrotic enteritis. This study evaluated body weight, feed intake, relative organ weights, hematological and serum biochemical parameters and performed histopathological examinations of liver, kidney and intestine. All the obtained data was statistically analyzed (P≤0.05). The results demonstrated that B. licheniformis supplementation reduced the susceptibility to necrotic enteritis in broilers initially exposed to mycotoxins. Body weight and feed intake were significantly decreased in groups challenged with mycotoxins and necrotic enteritis, both individually and concurrently, compared to the control group. Relative weights of the liver, kidney and intestine were significantly higher in treatment groups. Hematological analysis revealed significantly lower erythrogram parameters (TEC, Hb, and PCV) in birds fed mycotoxin-contaminated feed, with or without necrotic enteritis. Hepatic and renal biomarkers were significantly elevated, and serum protein levels (total protein, albumin) were significantly lower. In contrast, birds supplemented with B. licheniformis and challenged with either mycotoxins or NE showed no significant differences in body weight, feed intake, erythrogram and leucogram compared to the control group. However, B. licheniformis did not mitigate these effects when supplemented in group with concurrent challenge of mycotoxins and NE, however, intensity of changes was reduced. In conclusion, B. licheniformis supplementation effectively alleviates the pathological changes induced by mycotoxins and necrotic enteritis when presented individually but is not sufficiently effective against the combined challenge of mycotoxins and necrotic enteritis.