scholarly journals Evaluation of Acute and Subacute Toxicities of Psidium guajava Methanolic Bark Extract: A Botanical with In Vitro Antiproliferative Potential

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hermione T. Manekeng ◽  
Armelle T. Mbaveng ◽  
Samuel A. Ntyam Mendo ◽  
Armel-Joseph D. Agokeng ◽  
Victor Kuete

The methanol crude extract of the bark of Psidium guajava (guava) previously displayed interesting cytotoxic effects on a panel of human cancer cell lines. In the present work, we plan to determine the toxicological effects of this guava botanical in Wistar rats. Acute oral toxicity of the extract was carried out by administration of a single dose of 5000 mg/kg body weight to female rats in 14 days. Subacute toxicity was conducted by oral administration of the extract at daily doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg body weight, respectively, while rats in the control group received no extract. After 28 days of treatment, animals were sacrificed for hematological and biochemical studies. In the acute toxicity study, no mortality or signs of toxicity were recorded; hence, the median lethal dose (LD50) of the Psidium guajava bark extract is greater than 5000 mg/kg body weight. For the subacute toxicity study, significant variations in body weight, relative weight of organs, and biochemical parameters were observed in the animals treated at different doses of the plant extract compared to control animals. Histopathological analyses showed minor liver inflammation in females treated at the highest dose (1000 mg/kg). These results suggest that intake of a single high dose of the Psidium guajava bark extract is nontoxic, but repeat administration could exhibit mild organ toxicity.

2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.


Author(s):  
Liza Meutia Sari ◽  
Frans D Suyatna ◽  
Gus Permana Subita ◽  
Elza Ibrahim Auerkar

ABSTRACTObjective: Areca catechu Linn. or biji pinang is one of the most widely used psychoactive substance with several hundred million users worldwide,predominantly in Southern Asia. However, details of the dermal toxicity of A. catechu L. are still undiscovered. The objective of this study is toinvestigate the in vivo acute dermal toxicity of aqueous extract of A. catechu L. at dose 15,000 mg/kg body weight in Sprague-Dawley rats.Methods: The acute dermal toxicity of A. catechu L. nut extract was investigated in rats, as per OECD Guidelines 402 for acute toxicity protocols. Thebody weight, possibility of death, general signs, and behavior activity parameters were measured for 14 days to ascertain the median lethal dose(LD50) of the extract. At the end of the study, all the animals in all the treated group were sacrificed.Results: The LD50 was found to be >15,000 mg/kg body weight. There was significant weight increase (p<0.05) in treated group when comparedto control group. No mortality was observed during whole 14 days study period. A single dose of 15,000 mg/kg of body weight did not producetreatment-related signs of toxicity in any of animal tested.Conclusion: A single dermal dose to A. catechu L. aqueous extract had no toxic effects on mortality, clinical signs, body weight changes, and grossfindings in female rats at a dose of 15,000 mg/kg of body weight. Subsequently, the concentrate can be employed for pharmaceuticals nutrient plants.Keywords: A. catechu L., Acute dermal toxicity, LD50.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Million Loha ◽  
Abay Mulu ◽  
Solomon M. Abay ◽  
Wondwossen Ergete ◽  
Bekesho Geleta

Plant medicine is the oldest form of health care known to mankind. Syzygium guineense is one of the many species of Ethiopian medicinal plants which has a long history of use as remedies for various ailments such as dysentery, diarrhea, and hypertension. In many countries, herbal medicines and related products are introduced into the market without safety or toxicological evaluation. The aim of this study was to investigate the histopathological effect of 80% methanol extract of S. guineense on liver and kidney and blood parameters of rats. For acute toxicity study, rats were randomly divided into three groups (n=4). The control group received distilled water, while the experimental groups received a single dose of 2000 mg/kg and 5000 mg/kg 80% methanolic extract of S. guineense leaves per oral. For subacute toxicity study, the rats were randomly divided into three groups (n=6). The control group received distilled water, while the experimental groups received 500 mg/kg and 1500 mg/kg 80% methanol extract of S. guineense leaves orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluations. Gross pathology and histopathology of liver and kidneys were assessed. In the acute toxicity study, rats treated with 2000 mg/kg and 5000 mg/kg showed no toxicological signs observed on behavior, gross pathology, and body weight of rats. In the subacute toxicity study rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters, whereas both experimental groups had a lower blood glucose level compared with the control group (p < 0.05). There were no significant differences in the gross and histopathology of the liver and kidneys of experimental animals in extract exposed groups and their counterpart control. The 80% methanol extract of S. guineense does not produce adverse effects in rats after acute and subacute treatment. Before marketing a S. guineense leaf based remedy, subchronic and chronic toxicity evaluations need to be done.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Fentahun Adane ◽  
Kaleab Asres ◽  
Wondwossen Ergete ◽  
Samuel Woldekidan ◽  
Abiy Abebe ◽  
...  

Background. In Ethiopian traditional medicine, the aerial part of Thymus schimperi is widely used to treat diseases such as gonorrhea, cough, liver disease, kidney disease, hypertension, stomach pain, and fungal skin infections. However, there is insufficient investigation on the toxic effect of the essential oil of T. schimperi. The aim of this study was, therefore, to evaluate the acute, subacute, and in silico toxicity of Thymus schimperi essential oil in the Wistar albino rats. Method. Essential oil of the aerial part of T. schimperi extracted by hydrodistillation was analyzed by GC-MS. The oil was subjected to toxicity studies. In the acute toxicity study, rats were randomly divided into seven groups (n = 5). The control group received only distilled water with 2% of tween 80, whereas the experimental groups received single doses of 300, 600, 900, 1200, 1500, and 2 000 mg/kg of the oil. In the subacute toxicity study, rats were randomly divided into four groups (n = 10). The control group received distilled water with 2% of tween 80, whereas the experimental groups received 65 mg/kg, 130 mg/kg, and 260 mg/kg of the oil orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. Gross pathology and histopathology of the liver and the kidneys were also evaluated. For the in silico toxicity study, PubChem CID numbers of GC-MS identified bioactive compounds in the essential oil of T. schimperi obtained from PubChem. Chemdraw (8.0) was used to construct two-dimensional structures of the compounds. The Swiss ADMET web tool was used to convert the two-dimensional structures into a simplified molecular-input line input system (SMILES). In addition, the toxicity parameters were predicted via vNN and ADMET servers. Results. In this study, the LD50 of the essential oil of T. schimperi was found to be 1284.2 mg/kg. According to the World Health Organization, the oil is classified as moderately hazardous in its oral administration. In the subacute toxicity study, rats showed no significant changes in behavioral indices, gross pathology, body weight, biochemical, and most hematological parameters. However, hematological profiles showed a significant decrement in WBC counts and a significant increment of MCV in high dose (260 mg/kg) groups as compared to the control group. Furthermore, no significant differences were observed between the control and essential oil-treated groups, observed in the gross histopathology of the liver and the kidneys. In the in silico toxicity study, all compounds derived from the essential oil showed no cardiac toxicity (h-ERG Blocker), AMES (Ames Mutagenicity), and cytotoxicity via ADMET and vNN-ADMET toxicity predictors. However, by using these servers, about 8.6% of the compounds showed hepatotoxicity, only 3.45% caused drug-induced liver injury, and only 1.75% were potentially toxic to the mitochondrial membrane. Conclusion. From the results of this study, oral administration of the essential oil T. schimperi up to a dose of 130 mg/kg is not harmful. However, in the high-dose (260 mg/kg) group, the WBC count was significantly decreased and the MCV was significantly increased. In the in silico toxicity study, most of the components of the oil were found to be nontoxic, although a few of the compounds showed hepatotoxicity and mitochondrial membrane potential toxicity. It is, therefore, essential to conduct chronic toxicity of the essential oil as well as its components, which showed toxicity in the in silico study before using preparations containing the essential oil of T. schimperi.


2019 ◽  
Vol 8 (2) ◽  
pp. 1570-1576
Author(s):  
Kebe E. Obeten ◽  
Victor A. Fischer ◽  
Ugwuja O. Jennifer ◽  
Akim Bonaventure

The study was aimed at determining the effect of aqueous extract of Theobroma cacao on the histology of the ovary of female albino wistar rat. Twenty-four (24) adult wistar female rats weighting about 100- 160g were used for this research work and were divided into three (3) groups of eight (8) animals each. Group A; control, Group B; low dose and Group C; high dose with eight (8) animals in each group. Control group received vital feed; the low dose group was administered 240mgkg body weight of Theobroma cacao extract and the high dose group was administered 500mgkg body weight of the test substance. Extract was given daily by oral gavage method for twenty-one (21) days. Twenty-four hours after the last administration, all animals in each group were sacrificed under chloroform anesthesia. The ovaries were harvested, weighed and fixed in 10% buffered formalin for histological studies. Results showed that following administration of extract of Theoboma cacao at these doses, an insignificant decrease in organ weight was observed. Histological observation showed few follicles as well as loss of the substance of granulose cell this could possibly suggest decrease in production of sex steroids in the ovary.Keywords: Theobroma Cacao, Ovary, Histology


2016 ◽  
Vol 35 (2) ◽  
pp. 222-242 ◽  
Author(s):  
Robert W. Kapp ◽  
Odete Mendes ◽  
Shambhu Roy ◽  
Robert S. McQuate ◽  
Richard Kraska

Tea from the leaves of guayusa ( Ilex guayusa) has a long history of consumption by Ecuadorian natives in regions where the plant is indigenous. The tea contains the methylxanthines caffeine and theobromine as well as chlorogenic acids, flavonoids, and sugars. Various studies were performed to evaluate the general and genetic toxicology of a standardized liquid concentrate of guayusa (GC). Guayusa concentrate was found to be negative in in vitro genotoxicity tests including the Ames test and a chromosome aberration study in human lymphocytes. The oral median lethal dose (LD50) of GC was >5,000 mg/kg for female rats. Guayusa concentrate was administered to male and female rats in a 90-day subchronic study at 1,200, 2,500, and 5,000 mg/kg/d of GC and a caffeine-positive control at 150 mg/kg/d corresponding to the amount of caffeine in the high-dose GC group. Effects observed in the GC-treated groups were comparable to those in the caffeine control group and included reductions in body weights, food efficiency, triglycerides values, and fat pad weights and increases in blood chemistry values for serum aspartate aminotransferase, serum alanine aminotransferase, and cholesterol and adaptive salivary gland hypertrophy. No signs of incremental toxicity due to any other components of guayusa were observed. The studies indicate no harmful effects of GC in these test systems.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammed Bourhia ◽  
Ayoub Lahmadi ◽  
Hafid Achtak ◽  
Ayoub Touis ◽  
Jamal Elbrahmi ◽  
...  

Ethnopharmacological Relevance. Aristolochia paucinervis (A. paucinervis) (Aristolochiaceae) is a plant frequently used in Moroccan alternative medicine. The aim of the current study is to investigate the phytochemical composition of rhizomes decoction of A. paucinervis (RDA) and to evaluate its acute and subacute toxicity following the OECD guidelines. Materials and Methods. The qualitative phytochemical analysis of A. paucinervis was performed using standard qualitative phytochemical procedures. The acute toxicity of rhizomes decoction of the studied plant was evaluated in mice at single doses of 1, 2, and 4 g/kg of body weight for 14 days. In subacute toxicity study, the decoction was orally administered to mice at three different doses (0.5, 1, and 1.5 g/kg/day) for 28 days. Histopathological and biochemical parameters were investigated. Results. The preliminary phytochemical screening showed the presence of flavonoids, saponins, alkaloids, and polyphenols and the absence of anthraquinones, sterols, and terpenes. There was no mortality and no significant changes occurred in animals treated with 1 and 2 g/kg in the acute toxicity model. The signs of toxicity and morbidity were remarkable with the highest tested dose (4g/kg). LD50 (dose required to kill 50% of the test population) was determined as 4 g/kg. Repeated oral administration of 1 and 1.5 g/kg/day of RDA for 28 days induced significant disturbance of serum parameters (AST, ALT, LDH, urea, creatinine). Kidney and liver extracted from mice fed with 1 and 1.5 g/kg/day showed significant histopathological injuries as tubular necrosis, inflammatory infiltrate, tubular degeneration, necrosis, and hepatic cholestasis. Meanwhile, neither histopathological nor biochemical alterations were observed in mice treated with 0.5 g/kg/day of body weight in comparison to the control group. Conclusion. RDA showed toxicity in mice at a dose of 1 g/kg/day under subacute toxicity conditions. RDA is safe at a single dose inferior to 4 g/kg of body weight. The plant extract prepared by decoction showed more poisonous effect than the extract prepared by maceration at room temperature.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rupesh Shirodkar ◽  
Chandrasekhar Misra ◽  
Chethan GH ◽  
Pallavi Shetty ◽  
Zenab Attari ◽  
...  

The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 355-355
Author(s):  
Gizem Ozan ◽  
Alev Cumbul ◽  
Engin Sümer ◽  
Dilara Baban ◽  
Ahmet Aydın ◽  
...  

Abstract Objectives The intake of the high dose of polyphenols might cause adverse health effects on humans, in such cases, toxicological testing may be required to ensure safe levels of intake. In the present study, acute and subacute oral toxicity studies of polyphenol-rich European cranberrybush (Viburnum opulus L.) (ECB) fruit extract were evaluated to ensure the safe use of this extract. Methods In acute toxicity, freshly prepared ECB extract dissolved in distilled water was administrated to Sprague-Dawley rats by oral gavage at a single dose of 2000 mg/kg and signs of toxicity and mortality was observed. In subacute toxicity, Balb-c mice were administrated orally at 500 (low dose) and 2000 mg/kg (high dose) of ECB extract for 28 days and their mortality, clinical signs and, body weight were recorded on a daily and weekly basis, respectively. At the end of 28 days, while blood samples from each animal were taken for hematological and biochemical analysis, vital organs were taken for histopathological examination. Results In acute toxicity study, ECB extract showed no toxicological signs observed on behavioral change and body weight of rats after 14 days indicating that the lethal dose (LD50) of the ECB fruit extract might be higher than 2000 mg/kg. No death and no abnormal clinical signs were also recorded in subacute toxicity study. However, the increment in body weight of administrated high dose of ECB extract animals were significantly lower than control (P &gt; 0.05). High dose of ECB fruit extract induced the level of in some hematological parameters. Even amylase and lipase values were lower than normal ranges at high dose animals, other biochemical parameters results were not significantly different from the controls. In histopathological examination, the total histopathological scores ECB extract administrated mice at both doses were showed normal histological features in many tissues compared to control. However, administrated with a high dose of ECB extract showed significant changes in kidney, liver, and adipose tissue that were alterations (edema, infiltration, and bleeding) compared to control. Conclusions These findings indicated that polyphenol-rich ECB extract might show a toxic effect at a high dose (2000 mg/kg) and no observed adverse effect level (NOAEL) of ECB extract was 500 mg/kg ECB fruit juice. Funding Sources This study was supported by Yeditepe University.


Author(s):  
Vidushi Chaurasia ◽  
Madan Lal Aggarwal ◽  
Manoj Chandra Garg

Aims: The present experiment was conducted (comparative study) to determine the effect of single and repeated exposure of Penoxsulam herbicide by topical route. Study Design: To assess acute toxicity, rats were topically exposed by Penoxsulam at 2000 mg/kg body weight and all the animals were observed for 14 days experiment period while, in Subacute toxicity , the rats were topically exposed with Penoxsulam at three multiple dose levels; 200, 500, 1000 mg/kg body. weight once daily for 28 days. Place and Duration of Study: Toxicology department, Shriram Institute for Industrial Research, Delhi (INDIA), June 2018 and June 2019. Methodology: Acute study was carried out in 10 wistar rats and in subacute study the wistar rats were divided into 4 groups i.e., control group, low dose group, middle group, high dose group; 5 male and 5 female rats/ group at the age of 2-3 kg were exposed over a period of 28 days. After dose application the patch was removed and the test site were cleaned with cotton moistened with distilled water. Results: In both toxicity study found that there were no clinical signs of skin reactions (Draize method) and no significant P>0.05 changes were observed in Bodyweight, Biochemistry, and Histopathology among the treated as well as in control group of animals. Therefore, data of this study supports that topical exposure of Penoxsulam in rats were shown normal histology of liver, kidney, and skin at the multiple doses besides this; Penoxsulam does not have potential to produce acute and subacute adverse systemic toxic reaction to the animals. Conclusion: Therefore, data of this study supports that topical exposure of Penoxsulam in rats were shown normal histology of liver, kidney, and skin at the multiple doses besides this; Penoxsulam does not have potential to produce acute and subacute adverse systemic toxic reaction to the animals.


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