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Various studies suggest that mortality due to liver disease in diabetic patients is very high; however, the recognition of DM as the primary cause of chronic liver disease is neglected in medical practice, we therefore evaluated the activities of Sarcocephalus latifolius leaf powder on the liver function of alloxan – induced diabetic rats. Forty-five healthy female albino rats were randomly assigned into 9 different groups; diabetes was induced intraperitonealy with 160 mg/kg of alloxan. Normal and diabetic rats were administered orally with 300, 600, 750 mg/kg/ b.w of S. latifolius. After 28 days, the animals were sacrificed for biochemical and histological studies. The body weight of the normal and diabetic rats increased significantly with S. latifolius treatment, the increase observed in the blood glucose was brought down upon treatment with S. latifolius leaf powder. The activity of ALT increased significantly with 750 mg/kg of S. latifolius leaf powder, while low dose of the plant decreased it significantly in diabetic rats. GGT activity only decreased in the diabetic rats treated with 300 mg/kg of S. latifolius whereas albumin increased significantly (p

Acute and subacute toxicity tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by β-galactosidase derived from Bacillus circulans. Toxicity was evaluated by single dose oral administration (5,000 mg/kg) and was repeated at day 28 (1,000 mg/kg) in male and female Sprague-Dawley rats. In acute toxicity tests, the protein levels of male rats administered GOS showed a significant difference from controls, but remained within the normal range. There were no GOS-related changes in clinical symptoms, weight, food intake, hematology, blood chemistry, relative organ weight, or severe pathology in rats treated with GOS compared with controls. The no observed adverse effect level of GOS was at least 1,000 mg/kg/d in both male and female rats. Bovine-specific genes were not detected in GOS 70%-based products (NeoGOS-P70, NeoGOS-L70, and organic GOS), indirectly showing the absence of an allergen and that products containing GOS 70% are non-toxic and allergen-free.

Background and Aim: Some individuals in Indonesia consume intact goat gallbladder to prevent and treat malaria. The acute and subacute toxicity tests of goat bile (GB) have shown mild diarrhea in mice. Therefore, this study aimed to evaluate the suppressive effect of GB on parasitemia, splenomegaly, hepatomegaly, and blood biochemistry to assess liver and kidney function in BALB/c mice infected with Plasmodium berghei ANKA. Materials and Methods: Fifty healthy mice were infected with P. berghei ANKA and divided into five groups. Mice in three groups were administered 0.5 mL of 25%, 50%, or 100% of GB by gavage. Animals in Group 4 were administered 187.2 mg/kg BW of dihydroartemisinin-piperaquine phosphate as a positive control (POS Group). Mice in fifth group were administered sterile water as negative (NEG) controls. Further, 30 uninfected mice were divided into groups 6-8 and administered GB as were mice in the first three groups. Group 9 included 10 uninfected and untreated animals as healthy controls. Treatments were administered in a 4-day suppressive test followed by daily observation of Giemsa-stained blood smears. On day 7, mice were sacrificed to measure the length and weight of spleens and livers, plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine. Results: GB suppressed parasitemia but did not affect the size and weight of spleens or livers or plasma levels of AST and ALT compared to uninfected GB-treated and healthy control animals. Conversely, plasma levels of BUN and creatinine were suppressed and remained in the normal range in all groups of mice. Conclusion: GB suppresses parasitemia with no significant impact on hepatic enzymes in GB-treated infected mice. Liver dysfunction in GB-treated infected mice was due to P. berghei rather than GB treatment.

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

Background Food is the basic requirement and an essential part of all living beings which sustains life. A lot of emphasize has been given to food in the classics of Ayurveda and a detailed description of food which are both wholesome and unwholesome have been described. Viruddhahara (incompatible food) is a unique concept explained in Ayurveda which, in long run, may be harmful to the body. Objective(s) Intake of Kadaliphala (Musa paradisiaca. Linn, a variety of banana) and cow milk is an example of Samyoga Viruddha (incompatibility with reference to combination of things). This combination is routinely consumed by people. The present study was planned to evaluate the toxicological implication of their combination on wistar rats. Materials and methods A subacute toxicity study was conducted on Wistar rats following the repeated dose 28-day oral toxicity study in rodents, 407 - OECD guidelines. Different haematological and biochemical parameters along with histopathology of important organs were carried out to assess the toxicological implication of the combination. Results Repeated administration of the combination of Kadaliphala (Banana) and cow milk showed statistically significant increase in SGOT & urea and statistically significant decrease in creatinine. Significant decrease was observed in the food intake, faecal wet weight and faecal water in the 7th day of study, food conversion ratio in the 14th day of study, in the food intake, faecal wet weight and faecal water in the 21st day of study and significant decrease in the food conversion ratio in the 28th day of study. In histopathological examination, the test drug administered group showed mild to moderate myocarditis in the sections from heart. In sections from liver of two rats of test group, diffused micro fatty changes were observed. In sections from spleen; mild to moderate increase in the white pulp portion was observed. Conclusion Marked variation in SGOT, urea and creatinine levels and alteration in sections of heart, liver and spleen are indicative of mild toxicological implications of the combination of banana and milk. Continuous intake of this incompatible combination may hence prove harmful to the body.

The current study was carried out to investigate the sub-acute toxicity of 3-O--D-glucopyranosyl-(24)-ethylcholesta-5,22,25-triene, a steroidal glycoside isolated from the flowers of Alangium salviifolium Wang on Long Evan’s rat. After intra-peritoneal administration of the compound at a dose of 300 μg/rat/day for 14 consecutive days, no mortality or significant changes in body weight or behavior were observed. The blood samples of the rats were examined for hematological and biochemical parameters which were statistically insignificant when compared to that of the control group. All the vital organs showed normal histopathological architecture (heart, lungs, liver and kidney) in comparison to the control group. This preliminary investigation demonstrate that the compound is safe at dose of 300 μg/rat/day for 14 consecutive days. But acute, sub-chronic and chronic toxicity evaluations as well as clinical trials need to be done.

Background Gymnema sylvestre is a reputable medicinal plant commonly explore for the management of diabetes and other ailments in traditional medicine. In the present study, we investigated the phytochemical compositions and effect of crude extract, hexane, and ethyl-acetate fractions of Gymnema sylvestre on biochemical and hematological parameters of Wistar rats. Methods Albino rats were distributed randomly into a control group and nine treatment groups orally administered crude extract and fractions of Gymnema sylvestre (100, 300, and 600 mg/kg BW) for 21 days. Liver and kidney function indices, as well as hematological parameters, were monitored. Results Our results revealed that the crude methanol extract contains flavonoids (8.56 ± 0.50 mg/g), alkaloids (13.84 ± 0.67 mg/g), total phenol (1.98 ± 0.50 mg/g), saponins (23.85 ± 0.35 mg/g) and tannins (16.00 ± 0.34 mg/g). The crude methanol, ethyl acetate and n-hexane fractions of Gymnema sylvestre had LD50 greater than 5000 mg/kg BW in acute oral toxicity test. The extract and fractions at 300 and 600 mg/kg BW cause loss of body weight of the rats, significantly altered (p p > 0.05) alterations to the levels of biochemical and hematological parameters when compared with the non-treated control. Conclusion Gymnema sylvestre at sub-acute doses of 300 and 600 mg/kg BW could compromise the functional integrity of the rats’ liver and kidney. The study, therefore, suggested the use of Gymnema sylvestre for oral remedy at a dose of 100 mg/kg or below.

Pesticide usage has witnessed a rise in the current years to overcome the glitches of food scarcity because of incessant increase in population. Regardless of its extensive use in agriculture and related fields, these should be properly and thoroughly investigated because of unexplored danger which they bring along. The present investigation deals about the effects of one such pesticide, Permethrin, belonging to the class of synthetic pyrethroids, having broad range application in the field of agriculture, as an insect repellent, in lice shampoos, in the treatment of scabies and numerous other commercial uses. Although few reports have documented its adverse effect on the vital organs in different experimental models, there still persist lacunae in literature about its effect on the male reproductive tissue. Hence, the present study was aimed to evaluate the effects of Permethrin on the male reproductive gonad of Swiss albino mice. Permethrin (130 mg/kg body weight) was administered orally for a period of 21 days after which the biochemical parameters in testis were assayed. The results showed that Permethrin administration lowered the gravimetric indices (body weight p

The objective of present investigation was to synthesize and assess sub-acute toxicity of novel rosin esters using Swiss Albino mice. Assessment of the safety and toxicity of rosin esters is very important step before its use in pharmaceuticals. The solutions of rosin esters were prepared in corn oil to perform acute (28d) oral toxicity study in Swiss Albino mice as animal model of both sexes. The oral administration of rosin esters at the dose of 25 mg/kg of body weight and constant volume was administered to the mice. One group of mice was kept as a control group. Toxicity of the rosin esters was assessed by using various tests like behavioral changes, clinical signs, mortality and morbidity, biochemical tests, haematological tests, relative organ weights and histopathology tests. The body weights and food-water consumption by mice were recorded on weekly basis. The study results revealed that, there were no signs and incidences of toxicity or mortality in mice during the study period. No significant difference between treated (rosin ester administered) and control group of mice were recorded in the observations of different tests, body weights and food-water consumption. The histopathological examination of organs from the mice treated with rosin esters for 28d does not show any signs of toxic effects when compared with the control group. Therefore, the present investigation confirmed the non-toxic nature of novel rosin ester at 25mg/kg daily dose of body weight after oral administration in both the sexes.

Uji toksisitas merupakan salah satu tahap pengujian farmakologi yang harus dilakukan untuk menilai keamanan penggunaan suatu obat. Penelitian uji aktivitas ekstrak etanol daun Asam jawa (Tamrindus indica L) dosis 14 mg/200gBB sebagai antihiperglikemia terhadap hewan coba memberikan hasil yang tidak berbeda signifikan terhadap aktivitas obat standar Glibenklamid sebagai Antidiabetes mellitus, sehingga penelitian ini dilakukan dengan tujuan untuk melihat keamanan penggunaan dosis ekstrak etanol daun asam jawa (Tamrindus indica L) tersebut selama 30 hari terhadap kadar enzim AST, ALT, dan Kreatinin tikus (Rattus norvegicus). Pengujian toksisitas subakut ini menggunakan Hewan uji sebanyak 14 ekor dibagi 2 kelompok, tiap kelompok terdiri dari 7 ekor tikus. Kelompok I diberikan perlakuan Na CMC 0,5 % sebagai kontrol dan kelompok II diberikan perlakuan ekstrak etanol daun asam jawa dengan dosis 14 mg/200 g BB selama 30 hari. Pada hari ke-31 dilakukan pengukuran serum darah dengan parameter AST,ALT DAN kreatinin menggunakan alat humalyzer. Hasil pengujian toksisitas subakut menunjukkan bahwa pemberian ekstrak etanol daun asam jawa sebagai antihiperglikemia tidak menyebabkan peningkatan enzim AST,ALT DAN kreatinin melebihi batas normal.

The article presents the results of establishing the parameters of acute and subacute toxicity of the powder based on iodoform. Determination of acute toxicity parameters of the drug "Iodomin" were performed on 30 white mice 2-3 months of age, weighing 20-23 g and 30 white rats, aged 2-3 months, weighing 170-190 g. The drug was administered intragastrically, once, pre-dissolved in water. As a result of studies to determine acute toxicity by oral administration, it was found that, after administration of the drug in doses of 1000, 3000 and 5000 mg/kg, all animals remained alive. No changes in the clinical condition of the animals of the experimental groups were observed. The DL50 of ''Iodomin" powder is more than 5000 mg/kg. In conducted studies did not reveal the death of animals, respectively, the tested drug belongs to the IV class of toxicity (low toxicity). Studies on the determination of acute dermal toxicity of Iodomine were performed in accordance with the requirements of OECD № 402 (Acute Dermal Toxicity: Fixed Dose Procedure, 2017). Studies have shown that skin application of powder "Iodomin" at a dose of 2000 mg/kg body weight did not cause death, appearance of toxic effects. According to GHS the drug belongs to the 5th category. In the study of subacute toxicity, the drug was administered intragastrically, daily, pre-dissolved in water. On the 4th day of the experiment, in two experimental groups was a significant decrease in heart weight, which may be associated with functional load, and in group 2 (5-fold from therapeutic dose), along with that was a significant increase in liver mass, decreased concentration hemoglobin in the erythrocyte, creatinine in the blood, increased ALT activity. To determine the harmful effects of Iodomin powder on the mucous membrane of the eye were used 3 rabbits, to which the drug was administered in the amount of 2 drops in the conjunctival sac of the left eye. The harmful effect of the tested substance on the mucous membrane of the eyes was assessed by the appearance of hyperemia, edema and secretions according to the scoring system. When applying the suspension on the mucous membrane of the eye, it was found out, that after 24-48 hours the drug does not cause irritation. Also was found that the studied agent does not cause hyperemia, edema and changes in blood vessels. It's established that the powder "Iodomin" does not cause harmful effects on the mucous membranes of the eye.

A pigment-protein highly dominant in Spirulina is known as C-Phycocyanin. Earlier, in vitro studies has shown that C-phycocyanin is having many biological activities like antioxidant and anti-inflammatory activities, antiplatelet, hepatoprotective, and cholesterol-lowering properties. Interestingly, there are scanty in vivo experimental findings on the immunomodulatory and antioxidant effects of C-phycocyanin. This work is aimed at in vivo evaluation of the effects of C-phycocyanin on immunomodulation and antioxidant potential in Balb/c mice. Our results of in vivo toxicity, immunomodulatory and antioxidant effects of C-Phycocyanin suggests that C-phycocyanin is very safe for consumption and having substantial antioxidant potential and also possess immunomodulatory activities in Balb/c mice in a dosage dependent manner. C-phycocyanin doesn’t cause acute and subacute toxicity in the animal model (male, Balb/c mice) studied. We have reported that C-phycocyanin exhibited in vivo immunomodulation performance in this animal model.

Geum urbanum L. is a medicinal plant used from ancient time against gastro-intestinal disorders, bleeding and inflammation of mucous membranes, gums (gingivitis), etc. In our previous works, we demonstrated the antibacterial and antioxidant properties of ethyl acetate (EtOAc) extracts in vitro. The aim of this study was to evaluate the possibility of the EtOAc fraction from aerial parts to provoke acute and subacute toxicity by its internal daily administration (per os) in healthy H- albino male and female mice. We used three concentrations of treatment according to their biological activity potential of application − 20, 70 and 210 mg/kg. All animals were observed and recorded periodically for clinical signs, mortality and changes in their behavior (incl. hypo-activity, aggression, etc.). The body weight was measured at every 5 days up to the end of the experiment (a total 28 days). We studied the biochemical parameters (superoxide anion radical, hydrogen peroxide, superoxide dismutase, lipid peroxidation and damaged proteins in blood plasma and brain) and complete hematological parameters, and the histopathological findings in mouse spleens and Payer’s patches. The investigated extract did not show any signs of significant acute and subacute toxicity at the highest applied test-concentration, and therefore, we encouraged its possible application as food additive for various infectious diseases.

Objectives: Aluminum phosphide (AIP) is the commonly used pesticide in agriculture, which induces oxidative stress in almost all major body systems and organs. The aim of this study was to evaluate the efficacy of nanocurcumin and curcumin on serum oxidative stress level in subacute toxicity with AIP. Materials and Methods: In this study 36 male Wistar rats (220-250 g) were randomly divided into six groups. Control (C) receiving normal saline; group AIPreceiving AIP (2 mg/kg daily); group Cur receiving curcumin (100 mg/kg daily); group Nano-cur receiving nanocurcumin (100 mg/kg daily); group AIP+ Cur receiving AIP (2 mg/kg daily) and curcumin (100 mg/kg daily); and group AIP and Nano-cur receiving AIP (2 mg/kg daily) and nanocurcumin (100 mg/kg daily). Serum total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), and catalase (CAT) activity were measured. Results: AIP administration led to a significant increase in LPO, and decreased the CAT activity, TAC, and TTG compared to the control group (P

Acalypha wilkesiana has been used for various medicinal purposes such as in the treatment of hypertension, fungal and bacterial infections. In this study, the effects of prolonged oral administration of the aqueous leaf extract on some biochemical profiles of mice were evaluated. A total of 80 mice were allocated to 4 groups (A, B, C and D) comprising of 20 mice each. Mice in group A (control) were given (1 mL) of distilled water orally while 1 mL of the extract was given to the mice in groups B, C and D daily at the concentrations of 800, 1000 and 1200 mg/kg, respectively. This was continued for three weeks and at the end of each week, 4 mice from each group were humanely sacrificed and sera from blood samples collected were used for determination of activities of biochemical parameters. The results showed that administration of the extract resulted in significantly (p < 0.05) lower concentrations of total protein and cholesterol in the treatment groups at the 3rd week of treatment when compared to control values. Glucose level was significantly (p > 0.05) higher in the extract-treated groups by the 3rd week of treatment, while activities of AST, ALT and ALP were not significantly (p > 0.05) altered by the extract. There were no significant (p > 0.05) differences between the levels of calcium, total and conjugated bilirubin in treatment and control groups, while sodium concentration was significantly (p < 0.05) higher at day 14 after withdrawal of treatment, compared to the control. This study suggests that the extract of Acalypha wilkesiana has a hyperglycaemic effect.

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

Aim: To investigate the phytoconstituents of methanol and petroleum leaf extracts of Asystasia vogeliana (MLEAV and PLEAV), the median lethal dose (LD50) and the effects of MLEAV on body weight, organosomatic indices in vital organs and erythrocyte membrane of Albino Wistar rats during sub-acute administration. Place and Duration of Study: Department of Veterinary Physiology and Pharmacology, University of Nigeria, Nsukka, in 2017. Methodology: The crude extracts of MLEAV and PLEAV were used in determining the qualitative and quantitative analyses. The rats were assigned into four groups and dosed orally with distilled water (0.5 ml/100 g) as Group I, 62.5 mg/kg MLEAV (Group II), 125 mg/kg MLEAV (Group III) and 250 mg/kg MLEAV (Group IV) once daily for 28 days. Blood samples were collected from all the rats via the medial canthus into EDTA bottles for erythrocyte osmotic fragility (EOF) study on day 29. Relative organ-body weight indices of vital organs (spleen, heart, liver and kidney) were also evaluated. Results: MLEAV and PLEAV showed the presence of saponins, flavonoids, phenols, alkaloids, anthraquinones and steroids. The total phenolic contents of MLEAV (3704.30 ± 44.00) significantly increase (P = 0.000) when compared with PLEAV (1349.46 ± 35.25). The LD50 of MLEAV is above 5000 mg/kg. There were significant (P < 0.05) decreases in the body weights of rats in Groups III and IV from 3rd to 4th week when compared with their baseline weights. There were significant (P < 0.05) increases in the relative spleen-body weight in Group IV when compared with other groups. There was no significant change (P > 0.05) in the hemolysis of rats in Group II when compared with the control group at 0.9% NaCl concentration. Conclusions: The findings reveal that MLEAV showed better antioxidant capacity than PLEAV, and that 62.5 mg/kg of MLEAV is safe during the sub-acute administration.

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

The antiplasmodial and safety profile of alkaloid, flavonoid and phenol extracts of Sida acuta (300 and 600 mg/kgbw) on hepatic and renal integrity of rats were investigated. Alkaloid, flavonoid and phenol extracts produce parasitaemia suppression of 50.83%, 33.50% and 64.64%, respectively. Sub-chronic administration of the phytochemicals caused marked (p < 0.05) dose-dependent increase in erythrocytic and leucocytic indices while serum ALP, AST, ALT, albumin, urea and creatinine concentrations compared well (p > 0.05) with the controls. Total proteins, sodium and chloride levels were altered in rats treated with 300 mg/kgbw of the phytochemicals. The integrity of hepatocytes and renal cells increases with increase extract concentrations and no degenerative changes were observed in all treatment groups. However, flavonoid extract caused severe renal vacuolation at 300 mg/kgbw which cleared out at 600 mg/kgbw. Conclusively, phenol exhibited higher antiplasmodial activities and safety profile and thus could be considered a potential candidate for the development of a new drug.

Graphical abstract, Highlights • Novel anacardic acid loaded-zein nanoparticles were evaluated in terms of subacute toxicity and genotoxicity in Swiss mice. • The anacardic acid nanoparticles administered orally at 2.5 and 112.5 μg/Kg for 7 days did not present relevant toxicity. • These doses also presented a low frequency of micronuclei in the peripheral blood. • They showed good safety standards in mice under short-term treatments and could become novel therapeutic candidates., Anacardic acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing anacardic acid (9.375 μg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated anacardic acid at 2.25 and 112.5 μg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs’ relative weight reductions. Blank and anacardic acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.

Graphical abstract, Highlights • Recent research proves fucoidan to be very effective in the management of cancer and diabetes. • There are only limited information available on safety data with long term treatment of fucoidan. • This study reports the toxicity profile of fucoidan derived from Sargassum wightii greville for the first time. • 28 days repeated oral administration of fucoidan at the dose of 100, 200 and 400 mg/kg does not cause any significant organ toxicity., Objective The present study aimed to investigate the acute and subacute toxicity profile of fucoidan obtained from Sargassum wightii Greville, a brown marine algae in order to assess its safety. Methods Fucoidan was isolated from Sargassum wightii Greviile and subjected to FTIR analysis to confirm the functional groups. In acute toxicity study, a single dose of fucoidan (2000 mg/kg) was orally administered to three female rats as per OECD guideline 423. OECD guidelines 407 was adopted for subacute toxicity study. Fucoidan was orally administered to male and female rats at doses of 100, 200 and 400 mg/kg. Hematological, biochemical and histopathological analyses were carried out. Results FTIR analysis confirmed the presence of major functional groups. The animals did not show any remarkable toxic signs or mortality in acute toxicity study at single oral administration of fucoidan at the dose of 2000 mg/kg bodyweight. In subacute toxicity, no statistically significant difference in body weight, relative weight of vital organs, food and water intake compared to the control group was observed. Serum glucose and cholesterol showed a statistically significant reduction at all the doses when compared to normal control and the reduction was in a dose dependent manner. There were no other changes observed in biochemical or haematological parameters. Histopathological analysis showed no significant toxic signs at organ levels in treated groups when compared to normal control. Conclusions Based on the results obtained from acute and subacute toxicity study, fucoidan is considered to be safe in the models tested, which encourages its long term administration for medicinal uses. This study supports the application of fucoidan as a traditional medicine.

Made available in DSpace on 2022-05-01T09:47:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Doliocarpus dentatus (Dilleniaceae) has been used in folk medicine to treat inflammation and pain; however, studies evaluating its toxicity potential, as well as its effects on anxiety and depression, are scarce. This study investigated the toxicological profile of an ethanolic extract from leaves of D. dentatus (EEDd), and its effects on anxiety and depression models in mice. Male and female mice received either a single dose (500, 1000 or 2000 mg/kg) or repeated doses (75, 150 or 300 mg/kg) of EEDd by oral gavage. During the subacute toxicity assay, behavioral tests were performed on days 4, 14, 21 and 28. No evidence of toxicity was observed in the animals in both acute and subacute tests. However, males treated with the highest dose presented a reduction in the absolute weight of the kidney, an elevation in the AST levels, in addition to an alteration in the urea levels. The treatment did not affect other biochemical parameters, and did not induce any depressive-like behavior. EEDd exhibited low toxicity after single and repeated exposures. Since some analyzed parameters were compromised, further toxicity studies should be carried out. Faculty of Health Sciences Federal University of Grande Dourados Postgraduate Program in Chemistry Faculty of Exact Sciences and Technology Federal University of Grande Dourados Faculty of Health Sciences University Center of Grande Dourados Faculty of Exact and Agrarian Sciences University Center of Grande Dourados Center of Studies in Natural Resources State University of Mato Grosso Do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP–Paulista State University Pharmaceutical Sciences Food and Nutrition College Federal University of Mato Grosso do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP–Paulista State University

Background: Quercus serrata Murray leaves are traditionally used for the treatment of diabetes, dysmenorrhoea, inflammation and urinary tract infection. So, far no study has reported on the toxicological profile and antioxidant properties of the plant. Objective: The present study aimed to investigate the in-vivo toxicological profile and in-vitro antioxidant activities of the methanolic extract of standardized Quercus serrata leaves. Methods: Per-oral sub-acute toxicity study was performed in rats using three dose levels (200, 400 and 800 mg/kg b.w.) of the extract for 28 days. The control group received gum acacia suspended in water. Bodyweight was measured weekly. Biochemical parameters were analysed using the serum; the blood-cell count was performed using the whole blood. Pathological changes were also checked in highly perfused tissues. Further, in-vitro reducing power assay, nitric oxide scavenging assay, and DPPH free-radical scavenging assay were performed to evaluate the antioxidant activity of the extract. Results: There were no significant alterations found in the blood-cell count and biochemical parameters analysed in the treatment group when compared with the normal control. Histopathology study of liver, kidney, pancreas, heart and brain revealed normal cellular architecture in the treatment groups alike the control group animals. Quercus serrata also showed a significant reduction of DPPH with an IC50 value of 4.48±0.254 μg/mL, in-vitro reducing power activity with an IC50 value of 121.65±0.320 μg/mL and nitric oxide scavenging activity with an IC50 value of 106.43±0.338 μg/mL. Conclusion: The study showed that standardized methanolic extract of Quercus serrata leaves was safe after sub-acute oral administration in rats and possesses good antioxidant potential.

Bipyridine gold (III) dithiocarbamate compounds are Gold-III complexes with promising cytotoxic properties. In this study, the subacute toxicity of a Gold (III) complex with dithiocarbamate ligand was evaluated. In the acute toxicity component, an initial LD50 (38.46 mg/kg) was calculated by the administration of 50, 100, 200, 400, and 800 mg/kg of the compound to five groups of rats, respectively (n = 4 each). The sixth group was the control. The sub-acute toxicity component comprised the control group A (n = 6) and the study groups B (n = 10) and C (n = 4), which were administered 1 mL distilled water, 1/10 LD50 (3.8 mg/kg), and 1/5 LD50 (7.6 mg/kg), respectively, daily for 6 weeks. The alive animals were then sacrificed. Autopsy, preservation of renal, hepatic and cardiac tissue in buffered formalin, histopathological processing, microscopic evaluation, and comparison with the controls were sequentially conducted. In the subacute toxicity study at dosages of 3.8 mg/kg and 7.6 mg/kg, the renal tubules remained unaffected with no necrosis or vacuolization. Mild to moderate renal interstitial, hepatic capsular, lobular and portal inflammation along with mild focal hepatic vacuolization were present. At 3.8 mg/kg, the cardiac muscle fibers were unremarkable in 80% (n = 8) of the specimens, with mild focal hyalinization in 20% (n = 2) of the specimens. The same was observed in 50% (n = 2) of the specimens at 7.6 mg/kg. Variable congestion was evident in all of the groups. In the subacute toxicity study, the absence of renal tubular necrosis or vacuolization, the presence of mild inflammatory hepatic and renal alterations, and predominantly unremarkable cardiac muscle fibers suggest that Bipyridine gold (III)-dithiocarbamate is safe in animal studies and is a potential candidate for clinical trials.

Ganoderm applanatum is a polypore macrofungi and traditionally used as medicine rather than fodder. Silver nanoparticles mediated by G. applanatum extract were synthesized, characterized and toxicity impacts were investigated for their pharmacological and medicinal uses. The synthesized silver nanoparticles were of average 58.78 nm in diameter with -13.8 mV zetpotential, analysed by dynamic light scattering method. Fourier transform infrared spectroscopy analysis of synthesized nanoparticles confirmed the capping and stabilizing with mycochemicals, that showed transmittance at 3606 cm-1 corresponds to O-H stretch for phenol, 2430 cm-1 corresponds to N-H stretch for primary and secondary amines. 2000 mg kg-1, 200 mg kg-1 and 400 mg kg-1 doses of silver nanoparticles showed non-significant (p

Aims: The present study was carried out to investigate the toxic effects of the Oxalis barrelieri aqueous aerial parts extract. Place and Duration of Study: Department of Biological Sciences (Animal Physiology Laboratory), Higher Teachers’ Training College, University of Yaoundé I. Between April 2017 and June 2018. Materials and Methods: Acute toxicity using a single dose of 2000 mg/kg was administered to mice and effects were observed for 14 days. In sub-acute toxicity, the experimental rats (males and females) received aqueous extract of Oxalis barrelieri at doses of 200 mg/kg, 400 mg/kg and 800 mg/kg daily for 28 days while the control and satellite control groups received distilled water and satellite test group received extract at the dose of 800 mg/kg. The physical parameters were evaluated throughout the treatment, while the haematological, biochemical and histological parameters were evaluated at the end of the treatment. Results: In acute toxicity, the results obtained show no death and no significant variation (p>0.05) in behavioral and morphological parameters. In sub-acute toxicity assay, few modifications were observed in haematological and biochemical parameters. At the higher dose of extract (800 mg/kg),the rate of red blood cells decreased significantly (p

Ammi visnaga (Av) is a source of khellin where a tea made from the fruit of this plant was used as herbal medicine for kidney stones in Egypt. In the present research, the acute and subacute toxicity studies with oral intake of 150, 300 and 600 mg/kg of Av seed ethanolic extract in rats were done. In acute toxicity test, 4 groups of rats (n = 6/group: 3 males and 3 females) were chosen and the first control group received tap water, while the other three groups received Av seed ethanolic extract dissolved in tap water at doses of 150, 300, and 600 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, 72 rats (36 males and 36 females) were divided into 4 major groups; group I received tap water (control group), while animals in groups II, III, and IV (test groups) received oral intake of Av seed ethanolic extract dissolved in tap water at doses of 150, 300 and 600 mg/kg bwt, respectively. Each of this major group was subdivided consequently into 3 subgroups (n = 6/group: 3 males and 3 females) where brain tissue, blood sample, body and organs weights were recorded at the beginning and then after two and four weeks of the experiment for the determination of hematological, biochemical and histopathological changes in tissues (liver, kidney, brain, spleen, heart, testis and ovary). With regard to acute toxicity, Av seed ethanolic extract did not induce any toxic effects or death or any organ toxicity. In subacute toxicity study; oral intake with Av seed ethanolic extract did not reveal any change in body and organs weights, hematological parameters, serum glucose and cholesterol, brain neurotransmitters, liver and kidney functions, male and female hormones. In conclusion, Av seed ethanolic extract is nontoxic to liver, kidney, brain, spleen, heart, testis and ovary.

The safety of nanomaterials and nanotechnologies is an important factor in the regulation of industrial production and the introduction of nanoproducts into practice. The toxicological aspect of the use of silver nanoparticles (SNP) is insufficiently studied, leaving many questions without answer. The problem of dependence of toxicity on the shape and the size of nanoparticles is controversial and not well-studied, and there is a lack of research on the nanosilver effect on human and animal organisms. Objective. The aim of the work was to provide the hygienic assessment of harmful effects of silver nanoparticles of spherical and decahedron shape. Materials and Methods. Samples of solutions of spherical and decahedron SNP, synthesized by the method of photostimulated restoration, were intraperitoneally administered to white nonlinear rats both males and females aged 4 months. For the subacute toxicity study of spherical 45-nm nanosilver the animals were subdivided into three groups of (16 rats in each, 8 animals in a subgroup — according to gender). Every day they were injected with spherical SNP at doses of 0.1,1 and 5 mg/kg intraperitoneally for 14 days. The fourth group was the biological control. For the subacute toxicity study of decahedron 45-nm nanosilver the animals were subdivided into four groups (16 rats in each, 8 animals in the subgroup according to gender). The animals were injected intraperitoneally with 10, 5,1, and 0.1 mg/kg doses of SNP daily for 14 days. Fifth group was biological control. On 14th day animals were withdrawn from the experiment by decapitation under a slight, ethereal athetic. Results and Discussion. It was grounded the expediency of taking into account the physical and chemical properties of silver nanoparticles, including geometrical characteristics (shape, specific area of surface), the number of silver ions in nanoparticle and the quantity of nanoparticles in the solution while the determination of exposition of nanosilver or other nanochemicals of different geometric shapes. On models of subacute effect there were determined the peculiarities of different shapes nanosilver exposure and hygienic meaning of biochemical and pathomorphological changes as criteria of harmful effect. With the help of morphometric analysis of pathomorphological changes of internal organs of rats there was ascertained doserelated harmful effect of decahedron and spherical silver nanoparticles. As a result of the experiment, dose-dependent circulating swelling of the epithelium of convoluted tubules of the kidneys, hepatocytes, nuclei of cardiomyocytes, alteration of the epithelium of bronchi of different caliber, repletion of the blood vessels of the walls of the respiratory parts of the lungs, karyopicnosis of neurons of the cerebral cortex were observed. The revealed changes in the indices of prooxidant-antioxidant equilibrium, some biochemical indices and the changes in internal organs of animals testified to the less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. Conclusions. 1. According to the analysis of the geometric characteristics of decahedron silver nanoparticles, it is established that the specific area of decaheders is 2 times bigger than the specific area of the spherical SNP, which provides twice bigger area of the contact of silver nanodecahedron in the biological environment. The decahedron nanoparticle contains 4.3 times less atoms than spherical, and, at the same mass concentration, a solution of nanosilver contains 4 times more silver nano decahedrons than spheres. 2. With the help of biochemical analyses of blood and liver tissue, as well as the morphometric analysis of pathological changes in the internal organs of laboratory rats, the dose-dependent harmful effect of silver nanoparticles of decahedral and, partially, spherical shape was established. The revealed changes in the blood and internal organs of animals testified to a less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. 3. It was established that the differences in biochemical and pathomorphological changes in the internal organs of laboratory animals at the same dose of SNP the decahedron and spherical shape, calculated in mg/kg body weight, are related to a 4-multiple dose difference expressed in the ratio of «the number of nanoparticles/kg» of body weight and a 9-multiple difference in favor of nanodecahedrons while calculating the dose «specific surface area/kg» of body weight. Key Words: silver nanoparticles, silver nanodecahedron, silver nanosphere, toxicity, nanosilver.

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

A subacute toxicity test of 52.077 and 104.154 mg/L glyphosate-based herbicide (GBH) on common carp for 7 days was conducted. The results of qPCR reveled that GBH treatment generally promoted the H...

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD

In spite of high toxicological risk Aconitum napellus (ACON) is tremendously used for the treatment of rheumatoid and joint pain. The acute toxicity study was assessed for cow milk treated (CMT), g...

Made available in DSpace on 2019-10-06T16:23:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-04 Achyrocline satureioides (LAM) D.C. is a species plant used in folk medicine with several medicinal properties; however, few studies have focused on its potential adverse effects. The aim of this study was to examine the effects of ethanolic extract of A. satureioides flowers administered during pre-mating, mating, pregnancy and postpartum period on reproductive and developmental parameters in rats. Male and female rats received by gavage 0, 250, 500 or 750 mg/kg of extract. The animals were treated from pre-mating until 13 days post-partum. Phytochemical analysis revealed the presence of important flavonoids (quercetin, luteolin, caffeic acid, rutin, and ferulic acid). In females, biochemical, hematological or gestational parameters were not markedly altered by the extract. However, an increase in calcium and thyroid stimulating hormone (TSH) levels was found in treated-dams. Although TSH and T4 levels were not significantly altered in pups, there was a rise in body weight of pups whose mothers were treated with the extract. All males treated were able to successfully copulate with treated-females. However, rats exposed to 500 and 750 mg/kg of extract exhibited a significant decrease in daily testicular sperm production and delay in sperm transit time in the epididymis. The ethanolic extract of A. satureioides flowers produced adverse effects in the male reproductive system as evidenced by diminished sperm production and transport. In addition, the extract elevated TSH levels of exposed mothers which may consequently affect the development of pups but this requires further evaluation. School of Health Sciences Federal University of Grande Dourados Department of Morphology Institute of Biosciences of Botucatu UNESP –São Paulo State University Estadual Paulista Anhanguera Faculty of Dourados Center of Studies on Natural Resources Mato Grosso do Sul State University (UEMS) Department of Morphology Institute of Biosciences of Botucatu UNESP –São Paulo State University Estadual Paulista

S-[3-carbamoylsulfanyl-2-(dimethylamino)propyl] carbamothioate (Cartap) (CAS number: 15263-52-2) is a synthetic insecticide of thiocarbamates group that is extensively used in field of agriculture for controlling of several pests like rice stem borer, leaf folder pests in paddy field and diamond back moth, aphids in cabbage and cauliflower crops. Cartap, as a pesticide has not been investigated yet for its effect on vital organs and biochemical stress