Subacute Toxicity Research Articles

Inhibitory activity of nanoencapsulated quercetin against sodium arsenite-induced sub-acute liver toxicity in rats

Arsenic, a metalloid toxicant, is associated with a major global health problem as oxidative stress, a prime cause of tissue toxicity. The subject of our investigation was to assess the therapeutic efficiency of nanoencapsulated quercetin (QC) in combating sodium arsenite (NaAsO2)-inducted sub-acute hepatocellular toxicity in rat model. The rats of the hepatic damage group were injected subcutaneously (s.c.) four dosages of NaAsO2 (92.36 µM/kg b.wt.) twice a week. The rats of the polylactide nanoencapsulated QC group were injected intravenously (i.v.) four doses of nanoencapsulated QC (8.97 µmol/kg b.wt.) twice a week 2 h after the treatment (s.c.) with 92.36 µM /kg b. wt. NaAsO2 twice a week for four doses. The rats of the empty nanocasule or free QC treated group were injected i.v. four doses empty nanocapsule or free QC twice a week 2 h after the treatment (s.c.) with same doses of NaAsO2 twice a week for four doses. Arsenic deposition (580±20 µg/g protein) observed in liver tissue of rats treated with arsenite (92.36 µM/kg b.wt.), was found to reduce (120±9 µg/g protein) by the treatment of nanoencapsulated QC in rats significantly (p<0.001). The levels of antioxidant enzymes and GSSG/GSH ratio enhanced (p<0.001/0.1/0.01) by the treatment of NaAsO2 were reduced by the post treatment of nanoencapsulated QC significantly (p<0.001/0.01). The levels of ROS, lipohydroperoxide or membrane microviscosity increased or decreased (p<0.001) by the treatment of NaAsO2 were monitored to reduce or enhance significantly (p<0.001) by the treatment of nanoencapsulated QC in rat liver respectively. The blood serum biochemical levels enhanced (p<0.001) by the treatment of NaAsO2 were found to reduce significantly (p<0.001) by the treatment of nanoencapsulated QC in rats. The TGFβ1 and MMP-13 in the rat plasma augmented (p<0.001) by the treatment of NaAsO2-exposure were found to decline (p<0.001) significantly by the treatment of nanoencapsulated QC in rats. The rats in the other groups such as empty nanocapsule or free QC treated showed no or less inhibitory efficiency against NaAsO2-treatment compared to nanoencapsulated QC treated group. Application of nanoencapsulated QC may be a potent formulation to get higher inhibitory therapeutic efficiency against NaAsO2-induced sub-acute hepatocellular toxicity.

Subacute Toxicity Study of Alchornea cordifolia Ethanolic Leaf Extract on the Pituitary Gland of Wistar Rats

Introduction: Herbal medicines are plant-based products used to treat various illnesses and their uses have dramatically increased over the past years in many developed and developing nations. Alchornea cordifolia is one of these plants with reports of its use in health promotion. Some plants exhibit toxicity due to the presence of phytochemicals inherent in them, therefore further studies are necessary in evaluating their toxicity levels. In this study, the sub-acute toxicity of ethanolic extract of Alchornea cordifolia leaves was investigated on the pituitary gland of adult male Wistar rats. The objective was to determine its effect on the histology of the anterior pituitary gland. Methods: Twenty (20) adult male Wistar rats weighing 140-200 were used for the research and were randomly divided into four groups labelled A, B, C. and D. Each group consisted of five (5) rats. Group A (normal control) received normal saline, while group B, C and D received 500 mg/kg, 1,000 mg/kg and 1,500 mg/kg body weight of Alchornea cordifolia extract respectively with the aid of an oral gavage. This was done for a duration of 28 days after which the rats were sacrificed and the pituitary gland obtained for histological analysis using H&E and PAS Orange G staining methods. Results: Histological observations showed that the various doses of the extract used had no detrimental effect of the anterior pituitary gland microstructure in groups B, C, and D when compared to group A. Conclusion: The findings showed that the various doses of Alchornea cordifolia leaf extract used in this study are non-toxic to the anterior pituitary gland in Wistar rats.

Unraveling Water-Soluble Constituents of Basil (Ocimum basilicum L.) in Relation to Their Toxicity and Anti-Typhoidal Activity in Mouse Models.

Plants are the major source of natural flavour ingredients reported for their wide applications in food and pharmaceuticals, oral care and wellness products, etc. We have investigated the water-soluble fractions (WSF) of basil tetraploid (O. basilicum L.) for their toxicity and biological potential against Salmonella Typhimurium, a pathogen causing around one million cases of illnesses in the United States every year. The WSF obtained using a Clevenger-type apparatus was further divided into two equal parts, one each for in-vivo toxicity evaluation and quality assessments, respectively. The proportions of major phenylpropanoid identified as meta-eugenol in the WSF were found in the range of 42.8-57.9%, which was substantially in higher proportion as compared to essential oil (20.9-23.0%). Based on sub-acute oral toxicity data, WSF has not shown any adverse effect with levels as high as 500 µL/25g body weight in Swiss albino mice. Besides, the WSF also exhibited a maximum reduction in bacterial load in mice infected with Salmonella Typhimurium in a dose-dependent manner. We have shown the biological potential of basil water-soluble fraction as an effective bacterial load-suppressing agent for the prevention of Salmonella infections in animal model.

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.

Comprehensive genomic analysis and evaluation of in vivo and in vitro safety of Heyndrickxia coagulans BC99

This study aimed to evaluate the safety profile and beneficial effects of Heyndrickxia coagulans strain BC99 (BC99) for potential use in functional foods and pharmaceuticals. We began with whole genome sequencing of BC99, followed by a comprehensive safety assessment comprising genome analysis, hemolysis, cytotoxicity, antibiotic susceptibility tests, and cell adhesion and tolerance studies, along with acute and subacute oral toxicity studies in animal models. BC99 was isolated from a well-characterized collection originating from the feces of a healthy infant. Our results indicated no hemolytic activity on Columbia blood agar plates and broad antibiotic sensitivity, including to gentamicin, ampicillin, chloramphenicol, ciprofloxacin, and others. Cytotoxicity testing confirmed no adverse effects on HT-29 cells and significant adhesive properties to intestinal epithelial cells. Tolerance tests demonstrated over 90% viability of BC99 under simulated gastrointestinal conditions. In vivo studies in mice and rats confirmed the absence of adverse effects following oral administration. Collectively, these findings support BC99’s robust tolerance to gastrointestinal environments, strong adhesion capabilities, and a broad spectrum of antibiotic resistance, underlining its potential as a safe and effective agent for gut microbiota modulation and host health enhancement.

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.

Safety assessment and exploration of the mechanism of toxic effects of diallyl trisulfide: based on acute and subacute toxicity and proteomics experiments

Safety assessment and exploration of the mechanism of toxic effects of diallyl trisulfide: based on acute and subacute toxicity and proteomics experiments

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.

Bioavailability Improvement by Atomic Layer Coating: Fenofibrate A Case Study

Biopharmaceutical Classification Systems (BCS) class II drugs show poor solubility and high permeability in the body. Fenofibrate (FF) is a classic example of a BCS class II drug, used to treat high cholesterol and triglyceride (fat-like substances) levels in the blood. Atomic layer coating (ALC) is a surface engineering technology adapted from the semiconductor industry, where metal oxides are coated one atomic layer at a time over the active pharmaceutical ingredients (API) particles. ALC coating was proven to improve the processability, alter the hydrophilicity, improve the stability, and fine-tune the release of drugs. Herein, we report the intervention of ALC coating in enhancing the bioavailability of a poorly water-soluble drug (fenofibrate) in the animal model. The physical properties of uncoated fenofibrate were compared with those of zinc oxide-coated and silicon oxide-coated fenofibrate. Following the application of the coatings, the structural integrity (both chemical stability and solid-state stability) of the active pharmaceutical ingredient (API) remained uncompromised, as corroborated by 1H NMR and powder X-ray diffraction analyses. Notably, zinc oxide-coated fenofibrate exhibited favorable flow characteristics, whereas no discernible enhancement in flow behavior was observed for silicon oxide-coated fenofibrate. The results from contact angle measurements suggest that the silicon oxide-coated fenofibrate exhibits superior wetting behavior, as indicated by a contact angle nearing 0°. The application of ALC demonstrates an enhanced dissolution rate when compared to the uncoated active pharmaceutical ingredient (API) while leaving its equilibrium solubility unaffected. Coating the API with silicon oxide improves particle hydrophilicity and wetting properties, whereas zinc oxide coating aids in particle de-agglomeration, thereby enhancing their interaction with an aqueous medium. In vivo bioavailability studies conducted on rodents and larger animal (dog) models indicate a substantial increase in bioavailability (approximately 2 times) for the silicon oxide-coated API in comparison to the uncoated API, as determined by the area under the curve (AUC). Furthermore, the Cmax values for the silicon oxide-coated API also demonstrate a significant increase (approximately 3 times) over the uncoated API. Notably, an oral subacute toxicity study of ALC silicon-coated fenofibrate revealed no toxic effects attributable to the coating. This study underscores the potential of ALC in augmenting the bioavailability of BCS(II) drugs.

Nutritional Assessment and Sub-acute Toxicity Study in Wistar Rats Fed with a Compounded Diet of Roasted Plantain and Fish Sold in Otuoke, Nigeria

The widespread consumption of roasted plantain and fish (Bolle), a common delicacy in Bayelsa State has raised concerns over potential health risks associated with food processing contaminants such as acrylamides, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). The roasted plantain and fish are usually prepared by placing the peeled plantain and the dressed fish on a wired gauze and placed over a burning charcoal. The subacute toxicity study of this diet was investigated using twenty adult male rats averagely weighing 117.22 \(\pm\) 4.48 g. The rats were divided into four groups of five rats per group. Group A (Control), was fed with the standard rat chow, Group B; was fed with only the roasted plantain, Group C; was fed with only the roasted fish, and Group D; was fed with a combination of the roasted plantain and fish. The rats were given free access to the feed and portable water ad-libitum throughout the experimental protocol. Body/organ weight data were recorded before and after the completion of the experimental protocol. On day 15th of the experimental protocol, the rats were euthanized and blood specimens were obtained by cardiac puncture for biochemical analysis. The liver, kidney and heart were dissevered instantaneously and weighed. Findings from the study showed that the roasted plantain-fed group had significantly reduced body weight gain, and increased liver and kidney to body weight ratio (p>0.05). The plasma enzyme activity (AST, ALT and ALP) of the plantain-fed group were also significantly increased (p<0.05) while other groups showed non-significant differences (p>0.05) with the control group. The antioxidant status (CAT, SOD and GPx), haematological parameters (RBC, PCV, Hb, MCV, MCH, MCHC and platelet) of the plantain-fed groups were also significantly decreased (p<0.05) while other groups had non-significant changes (p>0.05) when compared to the control group. Malondialdehyde levels in the roasted plantain-fed group were also significantly increased (p<0.05).

Study of acute and subacute toxicities and genotoxic and mutagenic potentials of the lyophilized extract of Campomanesia sessiliflora (O.Berg) mattos leaves in wistar rats

Campomanesia sessiliflora (O.Berg) Mattos is a Brazilian native plant species used in a popular medicinal tea for treating gastrointestinal, urinary, and dermatological pathologies. This study evaluated the toxicity of Campomanesia sessiliflora (O.Berg) Mattos via acute and subacute toxicity tests. It also analyzed mutagenic and genotoxic potentials by the micronucleus test, which detects genetic material damage indicating mutagenicity, and the comet assay, which assesses DNA damage levels as a genotoxicity indicator. The plant extract initially originated from the ultrasonic maceration of Campomanesia sessiliflora (O.Berg) Mattos leaves in a hydroethanolic solution. The involved animals were adult Wistar rats. Ten females were available to evaluate acute toxicity and estimate the LD50, receiving a dose of 2000 mg/kg. The subacute toxicity evaluation used 35 females and 35 males divided into seven groups: negative control (saline control – SC), positive control (cyclophosphamide control – CC), 125 mg/kg (125), 250 mg/kg (250), 500 mg/kg (500), 1000 mg/kg (1000), and the satellite group (ST). Genotoxicity and mutagenicity experiments applied bone marrow micronucleus and comet assays. Acute and subacute toxicity tests did not present behavioral, physical, and physiological changes (p≥0.05). Administering the Campomanesia sessiliflora (O.Berg) Mattos extract reduced spleen size in male and female animals, without histopathological changes. However, doses above 500 mg/kg showed significant genotoxic and mutagenic effects in the comet and micronucleus assays compared to the control group. The extract did not exhibit acute or subacute toxicity, but doses higher than 500 mg/kg indicated some level of genotoxicity and mutagenicity.

Toxicological evaluation of LivLonga®, a polyherbal combination, in rodents

There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about Curcuma longa, Garcinia indica and Piper nigrum which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga® using in vivo models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.

Toxicological assessment of the aqueous extract of Juniperus oxycedrus L. on acute and subacute toxicities in rats

Juniperus oxycedrus L. (J. oxycedrus) has a rich historical background in herbal remedies to treating digestive system abnormalities. However, no comprehensive evaluation of its potential toxic effects has been conducted. The current investigation aimed to evaluate the acute and subacute toxicity of an aqueous extract of J. oxycedrus (AEJO). AEJO was prepared by the conventional Moroccan methods by decoction the arial part of the plant. The acute and subacute toxicity tests were conducted in mice and rats, respectively. Acute toxicity tests showed that the extract was not toxic even at high doses of 5000 mg/kg. In the subacute study, no detectable indications of toxicity or mortality were observed and there were no notable deviations in food intake or water consumption among all rats. However, changes in body weight of animals treated with 1000 and 2000 mg/kg underwent a significant decrease. AEJO administration decreased platelet number, elevated levels of alanine aminotransferase and alkaline phosphatase, and reduced albumin levels. Histological examination revealed normal renal parenchyma despite increased creatinine. It also showed binucleation, and hepatocyte vacuolation. The results indicate that AEJO has considerable tolerance for consumption, but repeated use can affect hepatocytes and kidneys. Therefore, additional analyses, such as subchronic, chronic, and neurotoxic studies, are required before using this plant in clinical research.

Acute and sub-acute toxicity study of aqueous and methanol root extract of Tetracera alnifolia in male albino rats

The aim of this study was to assess the acute and sub-acute toxicity of aqueous and methanol extracts of the root of Tetracera alnifolia as well as the effects on some biochemical parameters in albino rats as many plants used in traditional medicine lack scientific and clinical evidence to support a better understanding of their safety and efficacy. Phytochemical screening and proximate analysis of the pulverised root of Tetracera alnifolia was carried out using previously reported protocol. Sub-acute toxicity study of each extract was done for 28 days followed by organs function tests and histopathology studies of the liver, kidney and heart. Evaluation of lipid profile and oxidative stress marker to ascertain the effect of each extract on lipid peroxidation and their antioxidant property was done after administration of 200 mg/Kg body weight of each extract for a period of thirty-five days. Acute toxicity study of each extract gave oral LD50 (rat) of greater than 5000 mg/kg body weight with no signs of toxicity. Sub-acute toxicity study showed both extracts were non-toxic to the liver, kidney, heart and blood at doses between 200 and 3000 mg/Kg body weight assessed by the respective organ function tests, hematological parameters, and histopathology study. However, higher doses seem toxic to the liver particularly at 5000 mg/kg B. W due to increase in plasma AST, ALT and ALP activities accompanied with reduced protein and albumin concentrations. Effects of each extracts at 200 mg/Kg body weight on some biochemical parameters revealed no significant difference in lipid profile parameters and no lipid peroxidation. Each extract may possess antioxidant property due to increase in catalase activity. The result from this research may help validate the safety of the oral use of this plant in traditional medicine.

Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA levels in C57BL/6 mice

The coronavirus pandemic has resulted in over 775 million cases and 7 million deaths worldwide, driving efforts to develop therapeutic strategies to control the viral infection. Therapeutic oligonucleotides have shown promise in treating many pathological conditions, including those of viral origin. The present study assessed the in vivo efficacy and safety of ASC1R, a novel therapeutic oligonucleotide of unconventional design targeting the conserved viral RdRp sequence essential for replication. In functional studies, ASC1R was administered to transfected C57BL/6 mice at doses of 1 and 10 mg/kg. Safety assessments included acute toxicity evaluations at doses ranging from 30 to 100 mg/kg, and subacute toxicity evaluations of repeated doses of 1 and 10 mg/kg. Evaluations included general clinical observations, findings at necropsy, measurements of organ weight, and histopathological examinations of the liver, lungs, spleen, and kidneys. ASC1R effectively reduced RdRp levels >94 % within 24 hours following a single 1 mg/kg dose, with no observed organ toxicity. Acute and subacute toxicity assessments found that mice receiving high (≥30 mg/kg) or repeated (10 mg/kg for 7 days) doses of ASC1R showed an increase in relative spleen weight, without histopathological changes. The marked ability of a single low dose of ASC1R (1 mg/kg) to reduce viral RNA suggests its potential for clinical applications, balancing therapeutic efficacy with minimal side effects. Our findings indicate that ASC1R has promise as a viable treatment option for patients with COVID-19.

Evaluation of acute and subacute dermal toxicity of antibacterial bioactive glass-infused surgical cotton gauze in Wistar rats

Mesoporous bioactive glass, with its versatile characteristics and morphology, holds significant potential as an ideal hemostatic material. However, limited data is available regarding its toxicity levels. Consequently, this research intends to assess the acute and repeated dose dermal toxicity of Mesoporous antibacterial bioactive glass microsphere impregnated nonwoven surgical cotton gauze (MABGmscg) dressing in albino Wistar rats, following the standards set by the Organization for Economic Cooperation and Development. In the acute dermal toxicity study, the impact of MABG (@2000mg/kg BW) mscg dressing was assessed following a single dermal application in both male and female Wistar rats (n = 10). Mortality, clinical signs, body weight fluctuations and gross observations were consistently monitored over a14 day period following the single dose. The results indicated that, MABG (@2000mg/kg BW) mscg dressing upon dermal exposure did not cause any adverse effect in acute dermal toxicity study in Wistar rats compared to control group. Given that 2000 mg/kg BW of MABG was deemed a nontoxic dose, a repeated dose dermal toxicity study of MABGmscg dressing was subsequently conducted at three dose levels (@200, 500, 1000 mg/kg BW) over 28 consecutive days in Wistar rats. During the study period, no unscheduled deaths occurred, and there were no clinical signs associated with treatment, body weight variations or abnormal gross findings at necropsy in any groups. The analysis concluded that, MABGmscg dressing is safe to be considered as a hemostatic dressing at the various tested dose levels in Wistar rats.

Exploring Saffron's Therapeutic Potential: Insights on Phytochemistry, Bioactivity, and Clinical Implications.

Saffron, derived from the Crocus sativus plant, has been revered for centuries for its culinary, medicinal, and cultural significance. This review provides a comprehensive overview of saffron's chemical constituents and phytochemistry, elucidating its rich profile of bioactive compounds. Emphasis is placed on exploring the bio-accessibility, bioavailability, and bioactivity of saffron's phytochemicals, laying the foundation for understanding its pharmaceutical significance. The pharmaceutical importance of saffron and its phytochemicals is thoroughly examined, focusing on their diverse therapeutic properties. These include anticancer, antidiabetic, antioxidant, antimicrobial, anti-inflammatory, antinociceptive, anticonvulsant, antidepressant, learning and memory enhancement, cardiovascular, and antihypertensive properties. Such multifaceted pharmacological activities underscore saffron's potential as a valuable medicinal resource. Clinical studies investigating the efficacy and safety of saffron in various health conditions are synthesized, providing insights into its clinical applications. Moreover, toxicity assessments in animal models, encompassing acute, subacute, subchronic, and developmental toxicity, are discussed to delineate the safety profile of saffron and its bioactive constituents. Finally, recent advances and future perspectives in saffron research are highlighted, underscoring emerging trends and potential avenues for further exploration. This review serves as a comprehensive resource for researchers, clinicians, and stakeholders interested in harnessing the therapeutic potential of saffron while ensuring its safe and effective utilization in healthcare settings.

Sub-Acute Toxicity Assay of the smoke of Seeds of Azadirachta indica and Peels of Citrus sinensis used as natural insecticides on the Liver, Kidney, Lungs and Heart of Albino Rats

Abstract Natural plant parts such as seeds of Azadirachta indica (neem seeds) and peels of Citrus sinensis (sweet orange) have been used as house-hold remedies against various ailments and bio-pesticides for agricultural purpose due to their repellent, growth regulatory and anti-feedant properties against insects. Despite their beneficial role, these natural insecticides could also have toxic effects on some vital organs of human. Therefore, this study aimed to investigate the sub-acute toxicity of smoke of the Seeds of Azadirachta indica and Peels of Citrus sinensis on the liver, kidney, lungs and heart of swiss albino rats. In this study, three groups of white swiss albino rats were exposed to the smoke of A indica seeds, peels of C sinensis and their combination at different duration of one hour and two hours respectively. The Control group were not exposed to any of the natural insecticides and were fed normal diet and water. After four weeks of the treatment, the animals were all sacrificed and their liver, kidneys, lung and heart were evaluated using standard biochemical and histopathological techniques. The levels of serum biochemical indices for liver (aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin and protein), kidneys (urea, creatinine and electrolytes), and heart (creatine kinase and lactate dehydrogenase) were found to be significantly higher at (p<0.05) for all the groups treated with the two natural insecticides when compared to control group. Histopathological changes including fibrosis, hemorrhages, vascular congestion and necrosis were observed in the liver, kidneys and lungs tissues of the rats exposed to the smoke of the seeds of A indica. However, no histopathological changes were observed in all organs of rats exposed to the smoke of the peels of C sinensis compared to control group. Moreover, the severity of the effects of smoke of these natural insecticides on both biochemical and histopathological indices increases with increase in duration of exposure. The results of this study revealed that seeds of A indica have significant toxic effects on both the tissue and biochemical markers of all the major organs of the Swiss albino rats, while peels of C sinensis shows effect on only the biochemical indices at the specific duration of time studied.

Genotoxicity and safety profile of Eleview®: A submucosal injectable composition for endoscopic mucosal resection and endoscopic submucosal dissection

Background and Objectives: Eleview® submucosal injectable composition with methylene blue (MB), is intended for use in gastrointestinal endoscopic procedures. Given the recognised in vitro mutagenicity of MB, Eleview® mutagenic and genotoxic potentials and its safety profile in acute and subacute toxicity settings were assessed. Methods: Acute and subacute systemic toxicity were tested in rats and dogs, respectively. Ames test and chromosome aberration test in Chinese Hamster V79 cells, were performed. The ratio of polychromatic to normochromatic erythrocytes was assessed in rat bone marrow at the rat MTD. Results: Eleview® oral or intraperitoneal at 20 mL/kg or 50 mL/kg did not induce any acute toxic effects in rats. In dogs, Eleview® (15 mL) did not cause any relevant in-life observations or any histopathological changes in any organs/tissues or injection sites. Ames test demonstrated no concentration-related and reproducible increases in revertant colony numbers. No significant increase of chromosomally aberrant cells was noted in Chinese Hamster cells. Lastly, Eleview® did not elicit significant increase in micronucleated polychromatic erythrocyte frequency. Conclusion: No death or abnormal findings in the acute and subacute studies were observed for Eleview® administration. Eleview® is not genotoxic, nor mutagenic, proving to be a safe medical device to use in clinical practice.