Thirteen-Week Repeated Dose Oral Toxicity Study of Coenzyme Q10 in Rats

Honda, Kumiko; Tominaga, Sayumi; Oshikata, Takafumi; Kamiya, Kouichi; Hamamura, Masao; Kawasaki, Tsuneshirou; Wakigawa, Kouichi

doi:10.2131/jts.32.437

Cited by 10 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hyperlipidemia is a possible consequence of prolonged use of ubiquinone. This result was reported by Honda and coworkers [13], who documented elevated blood phosholipids levels after 13 weeks of administration of ubiquinone. Therefore, this status of ubiquinone-induced hyperlipidemia could be a contributing factor that may trigger the hypertrophy of the parotid gland's serous acini, as stated in the experiment conducted in 2011 by Daskala et al [14].…”

Section: Discussionsupporting

confidence: 82%

Histopathological comparison of the salivary glands’ acini and striated ducts after experimental prolonged daily administration of oral ubiquinone doses in rats

Abdullah

Sedeeq

Azzubaidi

2021

Current Issues in Pharmacy and Medical Sciences

View full text Add to dashboard Cite

Also called coenzyme Q10 (CoQ10), Ubiquinone is a vitamin-like endogenously produced factor essential for Adenosine triphosphate (ATP) mitochondrial production. Several research studies have reported that the exogenous supplementation of CoQ10 can lead to excessive salivation, especially in patients complaining of dry mouth. The objective of this study was to investigate the effect of long-term daily use of CoQ10 on the salivary glands in experimental animals by comparing the diameters of the glandular acini and striated ducts of a CoQ10-treated group and a control group. Twenty-five white albino rats were randomly divided into two groups; the control group consisted of 10 rats, while the CoQ10-treated group comprised 15 rats. The latter received daily oral treatment of 300 mg/kg CoQ10 for six weeks. Samples of the parotid, submandibular and sublingual glands were then dissected and examined histologically for comparative measurement of the diameters of the glands’ acini and striated ducts. The CoQ10 treated group had mean diameters of the serous acini for the parotid (79.8±11.2 μm) and submandibular (81.07±13.5 μm) glands that were significantly higher (P<0.05) than their diameters in the control group (67.5±8.4 μm and 73.3±13.8 μm), respectively. However, the difference was not statistically significant when comparing the diameters of striated ducts of the CoQ10-treated group and the control group. Continuous and prolonged exposure to exogenous ubiquinone may cause hypertrophic dilation of the acini within the salivary glands, namely the parotid and submandibular glands, which might be the underlying mechanism for excessive salivation. This can be considered a reversible adaptive response.

show abstract

Section: Discussionsupporting

confidence: 82%

Histopathological comparison of the salivary glands’ acini and striated ducts after experimental prolonged daily administration of oral ubiquinone doses in rats

Abdullah

Sedeeq

Azzubaidi

2021

Current Issues in Pharmacy and Medical Sciences

View full text Add to dashboard Cite

show abstract

“…However, Honda et al reported no changes with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights, or histopathology at highest dose of 1200 mg/kg bw/day for 13 weeks oral CoQ10 administration in rats [22].…”

Section: Discussionmentioning

confidence: 99%

Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

Deshmukh

Venkataramaiah

Doreswamy

et al. 2019

Journal of Toxicology

View full text Add to dashboard Cite

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

show abstract

“…The dosage of CoQ10 is set according to the previous study [11,18]. It was also reported that the non-observed-adverse-effect level (NOAEL) of CoQ10 was considered to be 1200 mg/kg/day for male and female rats [32]. Therefore, it is considered that single administration of 25 mg/kg weight CoQ10 in this study has no toxicological effect.…”

Section: Discussionmentioning

confidence: 99%

Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone

Nashimoto

Takekawa

Takekuma

et al. 2020

Drug Metabolism and Pharmacokinetics

View full text Add to dashboard Cite

Thirteen-Week Repeated Dose Oral Toxicity Study of Coenzyme Q10 in Rats

Cited by 10 publications

References 26 publications

Histopathological comparison of the salivary glands’ acini and striated ducts after experimental prolonged daily administration of oral ubiquinone doses in rats

Histopathological comparison of the salivary glands’ acini and striated ducts after experimental prolonged daily administration of oral ubiquinone doses in rats

Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone

Contact Info

Product

Resources

About