Organ Weight Changes Research Articles

CD19 chimeric antigen receptor T cell therapy in leukemia xenograft mouse: Anti-leukemic efficacy, kinetics, and 4-week single-dose toxicity

CD19 Chimeric antigen receptor T (CAR-T) cell therapy has shown a promising response rate for relapsed/refractory B-cell malignancies. However, serious side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome arose in early case reports. Though several preclinical and clinical studies of CAR-T cell therapy have been reported, there is a lack of toxicological assessments. This study was carried out as a preclinical assessment of CD19 CAR-T cell therapy, including the anti-leukemic efficacy, kinetics in peripheral blood, and 4-week single-dose toxicity evaluation in leukemia xenograft mice. Leukemia xenograft mice model was established by injecting 1.0 × 105 cells/mouse of luciferase-labeled human B cell acute lymphoblastic leukemia (B-ALL) cell line via the tail vein, and after 3 days, 2.0 or 4.0 × 106 cells/mouse of CD19 CAR-T cells were injected intravenously. CD19 CAR-T cells showed significant anti-leukemic efficacy, showing inhibition of tumor progression in the bioluminescence-based in-vivo imaging system. In the kinetics study using qPCR, CAR-T cells peaked in peripheral blood on day 60 in males and day 30 in females. In a 4-week single-dose toxicity study, CD19 CAR-T cell injected groups showed no mortality and toxicological signs, or changes in body weight, food/water consumption, hematology, clinical chemistry, organ weights, and histopathology compared to control groups. These results suggested that 4.0 × 106 cells/mouse of CD19 CAR-T cells were effective in B-ALL xenograft mice without serious side effects, so the no-observed adverse effect level (NOAEL) was estimated to be higher than 4.0 × 106 cells/mouse, under the condition examined in the current study.

Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models.

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.

Risk assessment and environmental consequences of the use of the Allium-derived compound propyl-propane thiosulfonate (PTSO) in agrifood applications

The organosulfur compound propyl-propane thiosulfonate (PTSO), mainly found in Allium cepa, has a promising use in the agrifood industry. To confirm its safety for livestock, consumers, and environment, toxicological assessment is needed. In this regard, endocrine-disrupting chemicals (EDCs) are in the spotlight of research. Therefore, as part of the risk assessment of PTSO, in the present work, an in vivo study was performed in mice exposed to PTSO to investigate its potential reproductive toxicity considering fertility, genetic and endocrine endpoints. Five-weeks-old CD1 mice (80 males, 80 females) were exposed for 11 or 16 weeks (males or females, respectively) to different doses of PTSO (0, 14, 28 and 55 mg PTSO/kg b.w./day; 20 animals per group and sex) through the food pellets. No clinical observations or mortality and no changes in absolute organ weights and relative organ weights/body weight or brain ratios occurred during the study. The estrous cycle did not undergo any significant toxicologically relevant change. Most of the sex hormones displayed normal values. Some alterations in the expression of some genes related to reproduction is only observed in females, but they do not appear to have consequences in the development of sex organs. Docking results showed the impossibility of stable binding to estrogen and androgen receptors. Considering all the results obtained, the safe profile of PTSO can be confirmed for different agrifood applications at the conditions assayed.

Polyphenols-rich polyherbal mixture attenuates hepatorenal impairment, dyslipidaemia, oxidative stress and inflammation in alloxan-induced diabetic rats

ABSTRACT Effects of polyherbal mixture on hepatorenal injury and dyslipidaemia in alloxan-induced diabetic rats were evaluated. Alloxan monohydrate (120 mg/kg, i.p.) was injected into Wistar rats to induce diabetes. Animals were allotted to six groups (n = 6) and treatments were administered for consecutive six weeks as normal and diabetic controls, glibenclamide and polyherbal mixture (200, 400 and 600 mg/kg), respectively. Ameliorative effects of the polyherbal mixture were investigated by assessing FBG levels, changes in body and organ (liver and kidney) weights, biochemical parameters, oxidative stress along with inflammatory parameters in addition to histopathological examination of the liver and kidney. The results showed that alloxan-injected rats had significant (P < 0.05) hyperglycaemia in addition to elevated serum levels of hepatorenal injury indices (ALT, AST, ALP, bilirubin, total protein, albumin, creatinine, BUN and uric acid) and hyperlipidaemia evidenced by increased TC, TG, LDL-C, VLDL-C and decreased HDL-C levels. Furthermore, diabetes induction caused an increase in lipid peroxidation (MDA) and a reduction in antioxidant markers (SOD and CAT activities) as well as inflammation (TNF-α) in hepatic and renal tissues. Polyherbal mixture remarkably improved the aforementioned parameters in a dose-dependent manner. Histopathological findings supported the biochemical results. Conclusively, this study has provided novel insights into the efficacy of polyherbal mixtures in managing hyperglycaemia and its secondary complications in diabetes mellitus.

Anti-obesity effects of Camellia (Camellia oleifera Abel) oil treatment on high-fat diet-induced obesity in C57BL/6J mice.

In the current study, we investigated the effects of camellia oil and camellia oil infused with herbs (Camellia oleifera Abel) on obesity in obese mice fed a high-fat diet (HFD). The antioxidant activity of camellia oil in scavenging free radicals was investigated. Additionally, body and organ weight changes, serum and liver marker parameters, antioxidant enzyme activities, liver and epididymal fat histology, protein and gene expression associated with lipogenesis and hyperglycemia effect on adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, were examined in HFD-induced obese mice. The hepatic steatosis and epididymal fat were significantly reduced by the oral administration of camellia oil and herb-infused camellia oil. Moreover, hepatic and serum marker parameters such as total cholesterol, insulin, triglycerides, tumor necrosis factor-α, adiponectin, thiobarbituric acid reactive substances, aspartate aminotransferase, and alanine transaminase were beneficially impacted. Additionally, the activity of antioxidant enzymes also increased. Camellia oil and herb-infused camellia oil treatments reduced the expression of genes linked to hyperglycemia and lipogenesis via activation of AMPK phosphorylation. For many people, exercise poses an obstacle in the daily routine due to lack of ease, difficulty in maintaining consistency, and hard work. Camellia oil combined with herbs has anti-obesity and antihyperglycemic effects. These findings indicate that treatment with herb-infused camellia oil is most beneficial for elderly individuals who do not prefer frequent exercise.

Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project.

In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action.

The Protective Effect of Oxitard on Sperm Function and Antioxidant Status in Rats Exposed to Swimming Stress.

Infertility is a significant public health issue, but its impact on quality of life and treatment efficacy is limited. Modern medicine lacks safe and effective drugs for male infertility, while traditional medicine has explored herbal extracts like Oxitard, which contains multiple extracts and oils. This study aimed to investigate the effects of Oxitard on male rats exposed to swimming (SW) stress. Albino rats weighing 220-250 g were divided into five groups: control, SW stress, and SW treated with Oxitard at low, medium, and high doses of 250, 500, and 750 mg/kg/day, respectively. The rats were subjected to SW stress for 15 days and then assessed for body weight, reproductive organ weight, testosterone, antioxidant status, sperm function, and histological changes in the testes, seminal vesicles, and vas deferens. The results showed that SW stress significantly reduced body weight, seminal vesicle weight, testosterone levels, superoxide dismutase (SOD), catalase (CAT), sperm count, sperm motility, sperm viability, and significantly increased malondialdehyde (MDA) levels. The testes of the SW-stress group rats also showed a significant decrease in spermatogenesis and the number of seminiferous tubules containing sperm. In contrast, treatment with Oxitard, especially at the highest dose, demonstrated potent free radical scavenging activity, recovering antioxidant status, and sperm function. SW stress led to decreased sperm function, antioxidant status, and increased lipid peroxidation (LPO) in male rats. Oxitard treatment, particularly in high doses, showed a potential role as a free radical scavenger in treating oxidative stress (OS)-associated male infertility. Further studies are needed to investigate the individual components of Oxitard and conduct clinical trials in human subjects.

Acute toxicity of ethanol extracts of Gynura divaricata L. leaves on DDY mice

Gynura divaricata (L.) DC., a traditional medicinal herb, has been used for the treatment of many diseases such as bronchitis, pulmonary tuberculosis, pertussis, toothache, rheumatic, arthralgia, uterine bleeding and diabetes in folk medicine. Despite its widespread use, studies on its toxicological characteristics are still very limited. The aim of this research is to observe the acute toxicity of ethanol extract of Gynura divaricata on Deutscland Denken Yoken (DDY) mice. The acute toxicity of ethanol extract of Gynura divaricata leaves was evaluated by giving it orally to DDY mice at single doses of 625, 1250, 2500, and 5000 mg/kg bodyweight. Animals were observed for mortality, body weight changes, macroscopic organ and relative organ weight for the next 14 days, and analyzed with ANOVA and Duncan post hoc test (p&lt;0.05). The results shown ethanol extract of Gynura divaricata leaves did not caused deaths. The gross necropsy analysis did not reveal changes of the organs. Ethanol extract of Gynura divaricata also did not cause significant change in relative organ weight. In conclusions, ethanol extract of Gynura divaricata leaves acute administration were safe at the dose used ethnomedicinally and practically non-toxic. Higher doses may involve toxicological risks.

Safety evaluation of Amphora sp., a marine microalgal diatom isolated from the Cape coastal waters, South Africa

Recent studies have highlighted the huge potential of a marine diatom, Amphora sp. as an affordable food supplement with significant therapeutic activities, however, the safety of the microalgae for human consumption has not been evaluated. Thus, in this study the in vitro and in vivo toxicity profiles of Amphora sp. biomass as well as its extracts were investigated to facilitate its use in human nutrition. The in vitro toxicity profile was assessed through the brine shrimp lethality, cytotoxicity and mutagenicity assays while the in vivo study was carried out using a rat model. The microalgal extracts displayed no cytotoxicity on the PBMC and MCF-7 cell lines neither did it display any evidence of mutagenicity on the Salmonella typhimurium strains. Similarly, results from the acute toxicity assessment demonstrated no remarkable changes in body and organ weights, the biochemical parameters as well as in the histopathology of the murine liver, heart and kidneys. Specifically, it was recorded that the oral administration of Amphora sp. to a dosage level of 4000 mg/kg/BW was relatively non-toxic, thus providing a scientific basis for selecting a safe dose in future studies aimed at highlighting the potentials of the diatom in human nutrition.

A mixture of 13 pesticides, contaminants, and food additives below individual NOAELs produces histopathological and organ weight changes in rats

The current approach for the risk assessment of chemicals does not account for the complex human real-life exposure scenarios. Exposure to chemical mixtures in everyday life has raised scientific, regulatory, and societal concerns in recent years. Several studies aiming to identify the safety limits of chemical mixtures determined hazardous levels lower than those of separate chemicals. Following these observations, this study built on the standards set by the real-life risk simulation (RLRS) scenario and investigated the effect of long-term exposure (18 months) to a mixture of 13 chemicals (methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, butylparaben, bisphenol A and acacia gum) in adult rats. Animals were divided into four dosing groups [0xNOAEL (control), 0.0025xNOAEL (low dose—LD), 0.01xNOAEL (medium dose—MD) and 0.05xNOAEL (high dose-HD) (mg/kg BW/day)]. After 18 months of exposure, all animals were sacrificed, and their organs were harvested, weighed, and pathologically examined. While organ weight tended to be higher in males than in females, when sex and dose were taken into account, lungs and hearts from female rats had significantly greater weight than that of males. This discrepancy was more obvious in the LD group. Histopathology showed that long-term exposure to the chemical mixture selected for this study caused dose-dependent changes in all examined organs. The main organs that contribute to chemical biotransformation and clearance (liver, kidneys, and lungs) consistently presented histopathological changes following exposure to the chemical mixture. In conclusion, exposure to very low doses (below the NOAEL) of the tested mixture for 18 months induced histopathological lesions and cytotoxic effects in a dose and tissue-dependent manner.

Safety assessment of Spondias purpurea aqueous leaf extract (anacardiaceae): Acute and sub-chronic toxicity studies in wistar rats

This study aimed to assess the toxicological profile of aqueous leaf extract of S. purpurea (ALES) in Wistar rats. ALES was subjected to acute and sub-chronic toxicity studies which were conducted according to Lorke’s and Organization for Economic Co-operation and Development 408 guidelines respectively. The acute toxicity study was carried out in two phases within 48 hours. Sub-chronic (90 days) toxicity studies were conducted on 4 groups of rats each. The first group received 1mL/kg distilled water, Groups 2, 3 and 4 received ALES 250, 500 and 1000 mg/kg respectively. Preliminary phytochemical screening revealed the presence of saponins, steroids/triterpenes, flavonoids, tannins, alkaloids, and cardiac glycosides. The oral median lethal dose (LD50) of the extract in rats was established to be greater than 5000 mg/kg. Sub-chronic administration of ALES did not produce significant changes in body weights and relative organ weights of treated rats. Hematology results between control and treated groups for a 90-day period of administration of ALES were comparable, however there was a significant (p &lt; 0.05) increase in differential white blood cell at highest dose. Biochemical result, revealed a non-significant mean variations in levels of renal and hepatic parameters between the treated groups and their corresponding controls. However, there was a significant (p &lt; 0.05) dose dependent decrease in level of potassium and glucose for treated groups compared their respective control, also a non-dose dependent decrease in ALP at 500 mg/kg ALES group. Lipid parameters examined also showed a dose dependent decrease in cholesterol, triglyceride, and LDL level, however the decrease was significant for triglyceride at 500 mg/kg and 1000 mg/kg treatment group compared to control. Additionally, in comparison to control a non-significant increase in HDL level was observed for treatment groups. The Histological result showed slight alterations in brain, liver, kidney, lungs and uterus intensified with an increase in the doses of the extracts administered. These findings suggest that Spondias purpurea leaf extract is relatively safe on acute administration. However, long term administration of higher doses could result in mild toxic responses. Therefore, caution should be taken in long term administration of the extract.

Preclinical PET Imaging and Toxicity Study of a 68Ga-Functionalized Polymeric Cardiac Blood Pool Agent

Cardiac blood pool imaging is currently performed almost exclusively with 99mTc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope 68Ga is used, it can be applied repeatedly on the same day-for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with 68Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the 99mTc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application.

Histological Assessment and Antimicrobial Investigation of Pure Compound; 3,5,6,7- Tetrahydroxy-19-Vouacanoic Acid;(3β, 5α, 6β, 7β)-form,6,7-Dibenzoyl (Pulcherrimin A) Isolated from Caesalpinia pulcherrima Stem Bark

This study was aimed to investigate the histological effect and antimicrobial activity of a compound [3,5,6,7-tetrahydroxy-19-vouacanoic acid;(3β, 5α, 6β, 7β)-form,6,7-dibenzoyl] previously isolated from Caesalpinia pulcherrima stem bark prior to this study. Different doses (2, 4 and 8 mg/kg) of the compound was administered to Wistar rats (both sexes) for a 28-day period. After the 28-day administration, vital organs (liver, heart, kidney, lung, uterus and testes) were harvested from the animals to ascertain their organ weight variations and histology. Microbial activity of the compound was investigated (using zone of inhibition test and minimum inhibitory concentration) for the microorganisms (Bacillus subtilis, Klebsiella pneumoniae, P. aeruginosa, Staphylococcus aureus, Candida. albican and Trychophyton rubrum). The observed weight changes in organs for all treated groups in relative to control was not significant at p &lt; 0.05 and no observed toxic abnormalities for all organs in treated groups upon their gross examination in relative to control. Highest zone inhibition was observed at 100 mg/kg for all tested microorganisms (B. subtilis, K. pneumonia, P. aeruginosa, S. aureus, C. albican and T. rubrum). with their corresponding MICs 11, 13, 16, 33, 30 and 31 mg/ml respectively. This study suggeststhat the compound could be a potential candidate in view of developing new antimicrobial agent and potential novel drug as a vasodilator.

Short- and long-term cognitive and metabolic effects of medium-chain triglyceride supplementation in rats

Medium-chain triglycerides (MCT) possess neuroprotective properties. However, the long-term metabolic consequences of supplementing a regular diet with cognition-enhancing doses of MCT are largely unknown. We studied the effects of chronic (28 days) supplementation of regular diet with different doses of MCT oil (1, 3, or 6 g/kg/day) or water (control) on working memory (Y-maze), behavior in the Open Field, spatial learning (Morris water maze), and weight of internal organs in male Wistar 2.5-m.o. Rats. In a separate experiment, we evaluated acute (single gavage) and chronic (28 days) effects of MCT or lard supplementation (3 g/kg) on blood biochemical parameters. MCT-1 and MCT-3 doses improved working memory in YM. In MWM, MCT-6 treatment improved spatial memory. Chronic MCT-1 or MCT-3 treatment did not affect internal organ weight, while MCT-6 dose increased liver weight and the brown/white adipose tissue ratio. Acutely, MCT administration elevated blood β-hydroxybutyrate and malondialdehyde levels. Chronic MCT administration (3 g/kg) did not affect the blood levels of glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate, total and HDL cholesterol, triglycerides, malondialdehyde, and aspartate transaminase and alanine transaminase activities. Therefore, daily supplementation of standard feed with MCT resulted in mild intermittent ketosis. It improved working memory at lower concentrations without significant adverse side effects. At higher concentrations, it improved long-term spatial memory but also resulted in organ weight changes and is likely unsafe. These results highlight the importance of monitoring the metabolic effects of MCT supplementation alongside cognitive assessment in future studies of MCT's neuroprotective properties.

Micro anatomical effects of aqueous cactus extract in the lungs of a diabetic Wistar rat

Opuntia stricta is a naturally occurring plant and is readily available in some parts of Zambia where it is used for its decorative nature and its fruits consumed. This present laboratory based study was carried out to assess some micro anatomical effects of aqueous cactus on the lungs of a diabetic Wistar rat. The male adult Wistar rats (30) weighing between 160-200 g were indiscriminately classified into five groups consisting of 6 Wistar rats namely: control, diabetic control, Diabetes+ Metformin, Diabetes+ cactus and cactus only groups. Diabetes was induced with Streptozotocin dose 70 mg/kg BW and sustained increase in blood glucose levels after 72 hours and treatment commenced with aqueous cactus extract and Metformin with 100 mg/kg body weight respectively and was administered orally for 4 weeks . Blood glucose levels (mmol/L) were monitored. After 4 weeks of treatment the animals were sacrificed by euthanasia, the lungs were excised, weighed and fixed in 10% formal saline. Data was analyzed using Excel and one way ANOVA. p&lt;0.05 was considered significant. Change in body weight and relative organ weight of the Diabetic+ cactus and Diabetes + Metformin was significant when compared to diabetic group(p&lt;0.05). Diabetic + cactus became normoglycemic at week 3 and diabetic+ Metformin at week 4. The histological examination of the lungs of the diabetic rats showed disruption in cytoarchitecture with necrotic pneumocyte. Diabetic + cactus and Diabetes + Metformin showed no disruption in their cytoarchitecture and both had healthy pneumocyte present. Cactus only was similar to control. In conclusion, aqueous extract of Cactus showed ameliorative effects on the lung of adult male Wistar rats against the damage caused by diabetes.

Sub-acute toxicity effects of modified sago starch edible films intake on haematology, histopathology, body and organ weight changes in Sprague Dawley rats

The toxicity of edible film from modified sago starch was evaluated through a sub-acute toxicity study on Sprague Dawley rats. Rats were given edible film at concentrations of 2 and 5 g/kg bodyweight for 28 consecutive days. Control rats only received commercial pellets. No significant changes were observed in the weight of rats and internal organs in low and high dose groups as well as control groups (p&gt;0.05). The food intake was in a range of 15-19 g/week. The haematology analysis showed significantly higher haemoglobin (HBG), haematocrit (HCT) and red blood cells (RBC) in the high dose group of rats. Elevated haematocrit level might indicate a dehydrated condition in rats as a result of the significant reduction of fluid intake in low and high dose groups as compared to control rats. Besides haematology, observation of histopathology effects of edible film on rats with an experimental diet found insignificant vacuolation in hepatocytes. In conclusion, these results demonstrate that edible film from modified sago starch is safe and non-toxic for consumption at a low dose, 2 g/kg body weight based on the 28 days of sub-acute toxicity study.

Antifertility Potential of n-Butanol and Ethyl Acetate Extracts of Penicillium oxalicum OM282858 in Male Albino Rats as Biological Control Agents

Rodents cause significant damage to many crops, spread diseases, and pose a severe risk to public health. Several synthetic contraceptive agents are available for controlling rodents; however, their use is associated with toxic effects on non-target organisms. Penicillium oxalicum has several medical properties, but no reports were available on fertility. This study aimed to assess the antifertility potential of n-butanol and ethyl acetate extracts of P. oxalicum in adult male albino rats as biological control agents by lowering the population size of rodent pests. Rats were assigned into three groups (n = 36). The first control group (GI) was injected intraperitoneally with 0.5% dimethyl sulfoxide (DMSO). The second (GII) and third (GIII) groups were injected with a single dose of 200 mg/kg body weight (b.wt.) of n-butanol and ethyl acetate extracts of P. oxalicum intraperitoneally, respectively, after dissolving in 0.5% DMSO. Further, P. oxalicum was identified morphologically and molecularly and then submitted with accession number OM282858 to the National Center for Biotechnology Information (NCBI) GenBank. The antifertility potential of P. oxalicum was evaluated after 24 h (the injection period), 96 h, and 168 h (the recovery periods) of treatments. The effects of the treatments on organ weight, testicular histology, histomorphometry measurements, and sperm characteristics were assessed. Both P. oxalicum extracts caused changes in reproductive organ weights, testicular histology, histomorphometry measurements, and spermatogenic arrest accompanied by a significant decrease in the count of epididymal sperm and its motility and an increase in the percentage of sperm abnormalities during the injection and recovery periods. Thus, the results suggest that both P. oxalicum extract treatments cause suppression of fertility in adult male rats. Therefore, these outcomes are essential for public health, farming establishments, and vertebrate pest control managers.

Hydroalcoholic Extract of Rabbiteye Blueberry (Vaccinium ashei) Leaves Mitigates Unpredictable Chronic Mild Stress Model Inducing Depressive-Like Behavior in Rats.

Several studies reported that rabbiteye blueberry (Vaccinium ashei Reade) leaves present promising biological properties. To the best of our knowledge, no study investigated the possible application of their hydroalcoholic extract for treating mood disorders. Herein, we evaluated if the hydroalcoholic extract of rabbiteye blueberry (Vaccinium ashei Reade) leaves (HEV) promotes an antidepressant-like effect in rodents using chronic experimental approaches. The effect of repeated administration of HEV (50 mg/kg, p.o.) on the immobility time was assessed in the forced swimming test (FST) in an unpredictable chronic mild stress (UCMS) model. Repeated treatment with HEV reversed the depressive-like behavior induced by UCMS by reducing the immobility time. Besides, the exposure to HEV caused no changes in relative organ weights in rats submitted to UCMS. The results indicated that HEV administration presented antidepressant-like action devoid of toxic effects. Thus, it is possible to suggest its potential as a safe and accessible therapeutic tool in the management of depression and other related mood disorders.

Antimalarial and immunomodulatory potential of chalcone derivatives in experimental model of malaria

BackgroundMalaria is a complex issue due to the availability of few therapies and chemical families against Plasmodium and mosquitoes. There is increasing resistance to various drugs and insecticides in Plasmodium and in the vector. Additionally, human behaviors are responsible for promoting resistance as well as increasing the risk of exposure to infections. Chalcones and their derivatives have been widely explored for their antimalarial effects. In this context, new derivatives of chalcones have been evaluated for their antimalarial efficacy.MethodsBALB/c mice were infected with P. berghei NK-65. The efficacy of the three most potent chalcone derivations (1, 2, and 3) identified after an in vitro compound screening test was tested. The selected doses of 10 mg/kg, 20 mg/kg, and 10 mg/kg were studied by evaluating parasitemia, changes in temperature, body weights, organ weights, histopathological features, nitric oxide, cytokines, and ICAM-1 expression. Also, localization of parasites inside the two vital tissues involved during malaria infections was done through a transmission electron microscope.ResultsAll three chalcone derivative treated groups showed significant (p < 0.001) reductions in parasitemia levels on the fifth and eighth days of post-infection compared to the infected control. These derivatives were found to modulate the immune response in a P. berghei infected malaria mouse model with a significant reduction in IL-12 levels.ConclusionsThe present study indicates the potential inhibitory and immunomodulatory actions of chalcones against the rodent malarial parasite P. berghei.

The influence of phytogenic additive on the antioxidant capacity, immunity and liver functions in stress-induced male rats

Global animal feeding strategies have been modified due to several ecosystem changes that cause stress and decline in health, growth, and yields. According to the literature, natural additives have been fundamental to animal health from day to day. The present study measured changes in antioxidant status, immunity, liver functions and organ weights tested under stress conditions to determine whether dietary supplementation with phytogenic additive could provide beneficial effects. Forty-eight adult, male Sprague-Dawley rats were randomly separated into four groups; Control(C), Stress(S), Treatment(Tr), Treatment and Stress(TrS). Rats in groups Tr and TrS received phytogenic additive by adding into water (2mL/L) 5days a week for 28days. All rats were exposed to prolonged light phase conditions (18h light: 6h dark) for 14 days. Also, two chronic stresses, isolation and crowded environments, were applied to animals in the Stress and TrS groups. There was a significant decline in the oxidant status in untreated stress group, while phytogenic additive fed rats maintained a significantly higher total antioxidant status. This study also showed a significant increase in IL-4 and decrease in IFN-γ in the untreated Stress group compared to the Control group. There were increases in liver enzymes in the Stress group in comparison to the Control group. After the phytogenic treatment, there was an increase in the weight of the liver, intestine, brain and testes. In conclusion, this study showed that supplementation of phytogenic additive containing milk thistle and artichoke with choline, carnitine, vitamin E and melatonin describes the protective effects on antioxidant status, immunological parameters and liver functions under mixed stress conditions.