Subacute toxicity study of CKD-501, a novel thiazolidinedione, after 4-week repeated oral administration in mice

2013 ◽  
Vol 221 ◽  
pp. S255
Author(s):  
Kyoung-Sik Moon ◽  
Jung-Ho Noh ◽  
Yong-Bum Kim ◽  
Eun Ju Jeong ◽  
In-Chang Hwang ◽  
...  
Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2631
Author(s):  
Abdullahi Aliyu ◽  
Mohd Rosly Shaari ◽  
Nurul Syahirah Ahmad Sayuti ◽  
Mohd Farhan Hanif Reduan ◽  
Shanmugavelu Sithambaram ◽  
...  

This study investigated the leaves of Clinacanthus nutans for its bioactive compounds and acute and subacute toxicity effects of C. nutans ethanolic leaf extract (CELE) on blood, liver and kidneys of ICR mice. A total of 10 8-week-old female mice were divided into groups A (control) and B (2000 mg/kg) for the acute toxicity study. A single dose of 2000 mg/kg was administered to group B through oral gavage and mice were monitored for 14 days. In the subacute toxicity study, mice were divided into five groups: A (control), B (125 mg/kg), C (250 mg/kg), D (500 mg/kg) and E (1000 mg/kg). The extract was administered daily for 28 days via oral gavage. The mice were sacrificed, and samples were collected for analyses. Myricetin, orientin, isoorientin, vitexin, isovitexin, isookanin, apigenin and ferulic acid were identified in the extract. Twenty-eight days of continuous oral administration revealed significant increases (p < 0.05) in creatinine, ALT and moderate hepatic and renal necrosis in groups D and E. The study concluded that the lethal dose (LD50) of CELE in mice is greater than 2000 mg/kg and that repeated oral administrations of CELE for 28 days induced hepatic and renal toxicities at 1000 mg/kg in female ICR mice.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Loubna Kharchoufa ◽  
Mohamed Bouhrim ◽  
Noureddine Bencheikh ◽  
Soufiane El Assri ◽  
Asmae Amirou ◽  
...  

Ethnopharmacological Relevance. Haloxylon scoparium Pomel is a herbal medicine traditionally used for treating scorpions and snakebite, diabetes, and stomachache as well as several other diseases. No systematic study of the potential toxicity of the plant has been described. Aim of the Study. The current study is aimed at assessing the potential toxicity of Haloxylon scoparium Pomel through the acute and subacute toxicity tests. Materials and Methods. Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results. Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion. Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Abdelfattah EL Moussaoui ◽  
Mohammed Bourhia ◽  
Fatima Zahra Jawhari ◽  
Imane Es-safi ◽  
Syed Saeed Ali ◽  
...  

Background. Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. Objective. The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. Materials and Methods. The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. Results. The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. Conclusion. The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yingnan You ◽  
Yang Gao ◽  
Han Wang ◽  
Jingshu Li ◽  
Xiang Zhang ◽  
...  

Nicotinamide mononucleotide (NMN), a key precursory metabolite of NAD+, has been shown to elevate the cellular level of NAD+ and ameliorate various age-related diseases. Despite these progresses, systemic evaluation pertaining to the subacute toxicity of NMN remains to be determined. Here, we examine the subacute toxicity of NMN in mice and beagle dogs. Mice were gavaged with a saturated concentration of NMN solution at the maximum intragastric dose once or twice per day for 7 days. Dogs were gavaged twice per day for 14 days. In mice, NMN administrated once per day for 7 days is well tolerated with minimal deleterious effects. Upon higher dosage, we observe slightly increased level of alamine aminotransferase, while other biomarkers remain unchanged. Consistently, administration of NMN in beagle dogs only results in mild increases in creatinine and uric acid. Together, our study highlights the safety of NMN, providing a possible safe dose range for oral administration of NMN.


2020 ◽  
Vol 14 (3) ◽  
pp. 187-195
Author(s):  
Berhan Mengiste ◽  
Tizazu Zenebe ◽  
Kassahun Dires ◽  
Ermias Lulekal ◽  
Awol Mekonnen ◽  
...  

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.


2010 ◽  
pp. 125 ◽  
Author(s):  
Dirikolu ◽  
Thushara Chakkath ◽  
Susan Ball-Kell ◽  
Christy Elamma ◽  
Timothy M. Fan ◽  
...  

2019 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Thi Thoi Bui ◽  
Dai Quang Ngo ◽  
Van Loc Tran ◽  
Van Chien Tran ◽  
Thi Nga Nguyen ◽  
...  

Glipizide is a second generation of sulfonylurea with promising hypoglycemic activity. It acts by stimulating the release of insulin from β-cells of pancreas. Glipizide is absorbed rapidly, uniformly with good mean oral bioavailability. It offers several advantages such as swift and short action, high potency and also does not accumulate in plasma on repeated oral administration. In this paper we report the acute and subacute toxicity of glipizide on BALB/c albino mice. The results showed the safety of our synthesized products.


1985 ◽  
Vol 10 (4) ◽  
pp. 295-308 ◽  
Author(s):  
Kunitoshi MITSUMORI ◽  
Keizo MAITA ◽  
Tadashi KOSAKA ◽  
Teiji MIYAOKA ◽  
Yasuhiko SHIRASU

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