scholarly journals Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration

2020 ◽  
Vol 11 ◽  
Author(s):  
Yingnan You ◽  
Yang Gao ◽  
Han Wang ◽  
Jingshu Li ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Oral Administration ◽  
Dose Range ◽  
Cellular Level ◽  
Toxicity Study ◽  
Beagle Dogs ◽  
Subacute Toxicity ◽  
Nicotinamide Mononucleotide ◽  
Age Related ◽  
Safe Dose

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.

scholarly journals Subacute Oral Administration of Clinacanthus nutans Ethanolic Leaf Extract Induced Liver and Kidney Toxicities in ICR Mice

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2631
Author(s):  
Abdullahi Aliyu ◽  
Mohd Rosly Shaari ◽  
Nurul Syahirah Ahmad Sayuti ◽  
Mohd Farhan Hanif Reduan ◽  
Shanmugavelu Sithambaram ◽  
...  
Keyword(s):  
Oral Administration ◽  
Leaf Extract ◽  
Lethal Dose ◽  
Toxicity Study ◽  
Oral Gavage ◽  
Subacute Toxicity ◽  
Icr Mice ◽  
Clinacanthus Nutans ◽  
Group B ◽  
Ethanolic Leaf Extract

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.

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 ◽  
...  
Keyword(s):  
Oral Administration ◽  
Toxicity Study ◽  
Subacute Toxicity

scholarly journals Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Loubna Kharchoufa ◽  
Mohamed Bouhrim ◽  
Noureddine Bencheikh ◽  
Soufiane El Assri ◽  
Asmae Amirou ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Oral Administration ◽  
Aqueous Extract ◽  
Hematological Parameters ◽  
Toxicity Study ◽  
Toxicity Tests ◽  
Potential Toxicity ◽  
Histological Studies ◽  
Subacute Toxicity

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.

Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy.

1985 ◽  
Vol 3 (8) ◽  
pp. 1136-1141 ◽  
Author(s):  
J C Allen ◽  
R Gralla ◽  
L Reilly ◽  
M Kellick ◽  
C Young
Keyword(s):  
Older Adults ◽  
Clinical Trials ◽  
Cancer Chemotherapy ◽  
Randomized Clinical Trials ◽  
Dose Range ◽  
Toxicity Study ◽  
Dose Increase ◽  
Younger Adults ◽  
Nonrandomized Trial ◽  
Safe Dose

Prior studies in adults have shown that metoclopramide (MCP), when given in high intravenous (IV) doses (2 mg/kg), is a highly effective antiemetic for chemotherapy-induced vomiting. It is well-tolerated in older adults, but younger adults have an increased disposition to acute extrapyramidal reactions (EPRs). Before studying the efficacy of MCP as an antiemetic in children, we first had to establish the safe dose range. We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin (120 mg/m2) or cyclophosphamide (greater than 900 mg/m2), beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg. MCP was given every two hours for four doses beginning one-half hour before chemotherapy. To reduce the incidence of EPRs, we added concomitant diphenhydramine. In MCP doses less than 2 mg, toxicity was minimal. In doses greater than or equal to 2 mg, 4/27 (15%) had EPRs and 9/27 (33%) had akathisia. Children who received two consecutive days of MCP had a higher frequency of EPRs. Metoclopramide (2 mg/kg) had promising antiemetic efficacy in a preliminary nonrandomized trial. Chemotherapy-experienced children vomited fewer than five times in 9/21 (43%) trials, and new patients vomited fewer than five times in 7/10 (70%) trials. MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed. Chemotherapy-induced emesis has the same negative implications in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting randomized clinical trials in children.

scholarly journals Withania frutescens. L Extract: Phytochemical Characterization and Acute and Repeated Dose 28-Day Oral Toxicity Studies in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Abdelfattah EL Moussaoui ◽  
Mohammed Bourhia ◽  
Fatima Zahra Jawhari ◽  
Imane Es-safi ◽  
Syed Saeed Ali ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Oral Administration ◽  
Biochemical Parameters ◽  
Clinical Symptoms ◽  
Toxicity Study ◽  
Control Group ◽  
Oral Toxicity ◽  
Traditional Use ◽  
Subacute Toxicity ◽  
Acute Toxicity Study

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.

scholarly journals Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

2021 ◽  
Vol 22 (7) ◽  
pp. 3709
Author(s):  
Fiqri D. Khaidizar ◽  
Yasumasa Bessho ◽  
Yasukazu Nakahata
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
The Elderly ◽  
Cellular Level ◽  
Salvage Pathway ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nicotinamide Riboside ◽  
Nicotinamide Mononucleotide ◽  
Age Related ◽  
Rate Limiting ◽  
Over Time

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD+, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD+ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD+ production through the NAD+ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD+ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD+ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD+ biosynthesis pathways in mammals, the NAD+ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD+, have been developed so far. In this review, we will focus on the importance of NAD+ and the possible application of an activator of NAMPT to promote successive aging.

scholarly journals Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 300
Author(s):  
Chidambaram Ramanathan ◽  
Thomas Lackie ◽  
Drake H. Williams ◽  
Paul S. Simone ◽  
Yufeng Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Neurodegenerative Diseases ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Disease States ◽  
Nicotinamide Mononucleotide ◽  
Age Related ◽  
Mice Brain ◽  
The Brain

As a redox-sensitive coenzyme, nicotinamide adenine dinucleotide (NAD+) plays a central role in cellular energy metabolism and homeostasis. Low NAD+ levels are linked to multiple disease states, including age-related diseases, such as metabolic and neurodegenerative diseases. Consequently, restoring/increasing NAD+ levels in vivo has emerged as an important intervention targeting age-related neurodegenerative diseases. One of the widely studied approaches to increase NAD+ levels in vivo is accomplished by using NAD+ precursors, such as nicotinamide mononucleotide (NMN). Oral administration of NMN has been shown to successfully increase NAD+ levels in a variety of tissues; however, it remains unclear whether NMN can cross the blood–brain barrier to increase brain NAD+ levels. This study evaluated the effects of oral NMN administration on NAD+ levels in C57/B6J mice brain tissues. Our results demonstrate that oral gavage of 400 mg/kg NMN successfully increases brain NAD+ levels in mice after 45 min. These findings provide evidence that NMN may be used as an intervention to increase NAD+ levels in the brain.

Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

2019 ◽  
Vol 19 (3) ◽  
pp. 259-273 ◽  
Author(s):  
Neelam Kaushal ◽  
Divya Vohora ◽  
Rajinder K Jalali ◽  
Sujeet Jha
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Uric Acid ◽  
Bone Metabolism ◽  
Serum Uric Acid ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Mineral Density ◽  
Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

2020 ◽  
Vol 14 (3) ◽  
pp. 187-195
Author(s):  
Berhan Mengiste ◽  
Tizazu Zenebe ◽  
Kassahun Dires ◽  
Ermias Lulekal ◽  
Awol Mekonnen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Essential Oil ◽  
Eucalyptus Globulus ◽  
Biochemical Parameters ◽  
Skin Irritation ◽  
Toxicity Study ◽  
Subacute Toxicity ◽  
Acute Toxicity Study ◽  
Limit Test ◽  
Ointment Formulation

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.

Sign in / Sign up

Export Citation Format

Share Document