In vivo hepatotoxicity of chemically modified nanocellulose in rats

2019 ◽  
Vol 39 (2) ◽  
pp. 212-223 ◽  
Author(s):  
CA Otuechere ◽  
A Adewuyi ◽  
OL Adebayo ◽  
IA Ebigwei
Keyword(s):  
Body Weight ◽  
Relative Weight ◽  
High Dose ◽  
Hydroxyl Groups ◽  
Oral Toxicity ◽  
Tissue Samples ◽  
Liver Histopathology ◽  
Biological Functionality ◽  
Oxide Synthase

Chemical modification of cellulose is currently attracting attention as researchers attempt to take advantage of the abundance of hydroxyl groups on its surface to introduce extra biological functionality. However, the possible deleterious effect of exposure to functionalized nanocellulose (CSN) remains a concern. Therefore, this study aims to explore the potential mechanisms of hepatotoxicity of CSN modified with oxalate ester (NCD) in rats. A 7-day repeated oral toxicity study of NCD at the doses of 50 and 100 mg kg−1 body weight was conducted, and plasma and liver tissue samples were assayed using biochemical analysis, liver histopathology, and protein expression. NCD, at both doses, did not significantly ( p > 0.05) alter the relative weight of liver, alkaline phosphatase activity, and lipid peroxidation levels of the animals. However, NCD at the dose of 100 mg kg−1 body weight significantly elevated aspartate aminotransferase, alanine aminotransferase, and myeloperoxidase activities. NCD also enhanced the immunohistochemical expression of inducible nitric oxide synthase and Bcl-2-associated X protein in the liver of rats. Histological observations revealed necrosis and severe cellular infiltration at the high-dose treatment. Our study provides an experimental basis for the safe application of NCDs.

scholarly journals Acute Toxicity Study of Iron-21 Syrup in Female Wistar Rats

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2637-2643
Author(s):  
Kirti G Sahu ◽  
Manish P Deshmukh ◽  
Sukeshini B Lote ◽  
Ashish B Budrani ◽  
Deepak S Khobragade
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Oral Route ◽  
The Body ◽  
Control Group ◽  
Haematological Parameter ◽  
Oral Toxicity ◽  
Tissue Samples ◽  
Histopathological Studies

The iron-21 syrup is used for iron deficiency anaemia which supplies iron and calories a provide iron and calorie nutriment to recompense haemoglobin deprivation. The objective of this study is to determine acute oral toxicity of Iron-21 syrup in vivo in Wistar rats. Iron-21 Syrup formulation was given through the oral route. The syrup formulation was administered in three increasing doses of 3, 6 and 12 ml/kg body weight for concentration of 500, 1000 and 2000mg/kg respectively. The other group of rats designated as a control group was given the only vehicle orally. The test and control group contains five rats each. Tests, as well as control group rats, were sacrificed on the fifteenth day of treatment. The blood and tissue samples of test animals were sent for histopathological studies examination. Four parameters were observed throughout the study, and they are cage side observation, the effect to the body weight, haematological parameter and histopathology. All animals were survived till they sacrificed. No notable changes were found in behaviour, haematological and histopathology studies. The oral administration of Iron-21 Syrup is not shown any toxic effect in the animal at a given dose. Therefore, it is a safe remedy for human use.

scholarly journals A 90-Day Oral Toxicity of Hydroethanolic Root Extract of Carissa spinarum in Wistar Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Komlan M. Dossou-Yovo ◽  
Aboudoulatif Diallo ◽  
Povi Lawson-Evi ◽  
Yendubé T. Kantati ◽  
Tchin Darré ◽  
...  
Keyword(s):  
Body Weight ◽  
Biochemical Parameters ◽  
Wistar Rats ◽  
Hematological Parameters ◽  
Relative Weight ◽  
Control Group ◽  
Root Extract ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Significant Difference

Background. Herbal medication is a worldwide and ancient practice, mostly in developing countries, where a large part of the population is involved in this practice. Hence, studies must be conducted to evaluate their safety and efficiency to avoid or prevent toxicological risks due to their usage. In Togo, Carissa spinarum is a medicinal plant belonging to Apocynaceae family, used as an aphrodisiac or to heal some ailments including malaria, sickle cell anemia, hypertension, pain, and asthma. Notwithstanding its several ethnomedicinal benefits, just a few toxicological data associated with its chronic use are available. Objective. Therefore, this study aims to assess the toxicity of an ethanolic root extract of Carissa spinarum in Wistar rats. Methods. The 90-day oral toxicity process following OECD TG 408 guidelines is used. Male Wistar rats received Carissa spinarum root hydroethanolic extract at 500 and 1000 mg/kg for 90 days by oral gavage. Body weight changes, hematological and blood biochemical parameters, organ weight changes, malondialdehyde as a lipoperoxidation marker expressed according to tissue proteins, and histopathology of vital organs were assessed. Results. No signs of toxicity or mortality were observed during the 90 days experiment. Hematological parameters have not shown any treatment-related abnormalities. According to biochemical parameters, an increase in the chloride ion level was observed at 1000 mg/kg p < 0.01 . There was no significant difference between the treated groups and the control group concerning the malondialdehyde concentration, body weight, and organ relative weight. No changes in necropsy and histopathology of vital organs associated with extract treatment were observed. Conclusion. The results indicated that an ethanolic root extract of Carissa spinarum does not cause adverse effects, which can lead to Wistar rats’ death after 90-day oral administration at 500 and 1000 mg.

scholarly journals Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Kidney Stones ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Tribulus Terrestris ◽  
Oral Toxicity ◽  
Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

scholarly journals Toxicological Investigations of Aristolochia longa Root Extracts

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nasreddine El Omari ◽  
Omar El Blidi ◽  
Abdelhakim Bouyahya ◽  
Karima Sayah ◽  
Saad Bakrim ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Global Analysis ◽  
Clinical Signs ◽  
Experimental Period ◽  
High Dose ◽  
Herbaceous Plant ◽  
Oral Toxicity ◽  
Toxicity Potential ◽  
Liver And Kidney

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.

scholarly journals Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan
Keyword(s):  
Body Weight ◽  
Toxicity Study ◽  
Morphological Alteration ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Methanolic Extracts ◽  
Sprague Dawley Rats ◽  
Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

scholarly journals 90-Days Repeated Dose Oral Toxicity Study of Sharbat-e-Deenar (A Hepatoprotective Unani Herbal Formulation)

2021 ◽  
Author(s):  
Gulam Mohammed Husain ◽  
Tasleem Ahmad ◽  
Syeda Hajra Fatima ◽  
Ghazala Javed ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Function ◽  
Clinical Sign ◽  
Equivalent Dose ◽  
Toxicity Study ◽  
Feed Consumption ◽  
Repeated Dose ◽  
High Dose ◽  
Oral Toxicity ◽  
Dose Oral

Sharbat-e-Deenar (SDR) is a compound Unani pharmacopoeial formulation recommended for the treatment of Waram-e-Kabid (hepatitis), Waram-e-Rahem (uterine inflammation/ Pelvic Inflammatory Diseases), Yarqan-e-Suddi (obstructive jaundice), and Istisqa (ascites). The current study was carried out to investigate repeated dose oral toxicity study of SDR for 90 days in Sprague dawley (SD) rats. SDR was orally administered (gavage) at the doses of 4, 10 and 20 mL/kg bw/day. A periodic observation was performed for mortality, morbidity and any clinical sign of toxicity. Changes in body weight and feed consumption were observed weekly throughout study duration. After the treatment duration of three months, animals were anaesthetized and blood samples were subjected to haematological investigation and serum was subjected to different biochemical estimation. Gross necropsy was performed and internal organs/ tissues were processed for histopathological investigation. Treatment with SDR showed no incidence of mortality and no clinical sign of systemic toxicity. Body weight showed pattern of weight gain except significance decrease at mid and high dose at 13th week of study duration. Feed consumption exhibited a significant decrease as compare to control. Haematology and biochemistry profile found normal except certain isolated changes which was considered toxicologically not significant as the values lies in the normal physiological range. There were no changes observed in the gross necropsy and relative organ weight data of control and SDR treated rats. It is reported that few of the animals showed changes in liver at mid (2.5 times of therapeutic equivalent dose) and high dose (5 times of therapeutic equivalent dose) in SDR treated animals that may be attributed to SDR treatment, however, associated liver function parameters like ALT, AST and ALP did not show any alteration of liver function. Based on the results of this study, it may be indicated that liver may be the target organ for toxicity if SDR is used above recommended therapeutic dose for longer duration.

scholarly journals In Vivo and Ex Vivo Evaluation of 1,3-Thiazolidine-2,4-Dione Derivatives as Euglycemic Agents

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Diana Alemán-González-Duhart ◽  
Samuel Álvarez-Almazán ◽  
Miguel Valdes ◽  
Feliciano Tamay-Cach ◽  
Jessica Elena Mendieta-Wejebe
Keyword(s):  
Antioxidant Activity ◽  
Ex Vivo ◽  
Peroxisome Proliferator ◽  
Oral Toxicity ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tissue Samples ◽  
Design Synthesis ◽  
Antioxidant Agents ◽  
Male Wistar Rats

Thiazolidinediones (TZDs), used to treat type 2 diabetes mellitus, act as full agonists of the peroxisome proliferator-activated receptor gamma. Unfortunately, they produce adverse effects, including weight gain, hepatic toxicity, and heart failure. Our group previously reported the design, synthesis, in silico evaluation, and acute oral toxicity test of two TZD derivatives, compounds 40 (C40) and 81 (C81), characterized as category 5 and 4, respectively, under the Globally Harmonized System. The aim of this study was to determine whether C40, C81, and a new compound, C4, act as euglycemic and antioxidant agents in male Wistar rats with streptozotocin-induced diabetes. The animals were randomly divided into six groups ( n = 7 ): the control, those with diabetes and untreated, and those with diabetes and treated with pioglitazone, C40, C81, or C4 (daily for 21 days). At the end of the experiment, tissue samples were collected to quantify the level of glucose, insulin, triglycerides, total cholesterol, and liver enzymes, as well as enzymatic and nonenzymatic antioxidant activity. C4, without a hypoglycemic effect, displayed the best antioxidant activity. Whereas C81 could only attenuate the elevated level of blood glucose, C40 generated euglycemia by the end of the treatment. All compounds produced a significant decrease in triglycerides.

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
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Relative Weight ◽  
Psidium Guajava ◽  
Toxicity Study ◽  
Female Rats ◽  
Bark Extract ◽  
Control Group ◽  
High Dose ◽  
Subacute Toxicity

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.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

scholarly journals Toxicity Evaluation of Pũrṇa Cantirotaya Centũram, a Siddha Medicine in Wistar Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
B. Chitra ◽  
R. S. Ramaswamy ◽  
V. Suba
Keyword(s):  
Body Weight ◽  
Histopathological Examination ◽  
Toxicity Study ◽  
Repeated Dose ◽  
High Dose ◽  
Oral Toxicity ◽  
High Dose Level ◽  
Show Evidence ◽  
Dose Study ◽  
Acute Study

Pũrṇa Cantirotaya Centũram (PCC), a herbometallic formulation of Siddha medicine, consists of mercury, sulphur, and gold, processed with red cotton flower and plantain stem pith juices. To evaluate its safety, acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively. In acute study, PCC was administered orally at 5, 50, 300, and 2000 mg/kg body weight. Animals were observed for toxic signs for 14 days. Gross pathology was performed at the end of the study. In repeated dose toxicity study, PCC was administered at 2.5, 25, and 50 mg/kg body weight daily for 28 days. Satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of PCC. In acute toxicity study, no treatment related death or toxic signs were observed. It revealed that the LD50 cut-off value of PCC is between 2000 and 5000 mg/kg body weight. The repeated dose study did not show evidence of any treatment related changes in all observations up to the high dose level, when compared with the control. Histopathological examination revealed no abnormalities except mild hyperplasia of stomach in high dose group. This study provides scientific validation for the safety of PCC.

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