28-Day repeated dose toxicity study of dried microorganism in rats

Kitano, Mitsuaki; Hosoe, Kazunori; Fukutomi, Naoki; Hidaka, T; Imai, Norio; Kawabe, Mayumi

doi:10.1016/j.fct.2004.06.013

Cited by 10 publications

(5 citation statements)

References 6 publications

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“…In higher organisms, including humans, this compound has 10 isoprenoid units in its side chain and is therefore named Coenzyme-Q 10 (CoQ 10 ; Hathcock and Shao 2006). CoQ 10 , also known as Ubiquinone-Q 10 , is widely used as a therapeutic agent, a dietary supplement, an ingredient in cosmetic products, and various other products (Kitano et al 2004;Müller et al 2007;Ochiai et al 2007). CoQ 10 is a lipid-soluble compound located in the inner mitochondrial membrane where it functions as a part of the electron transport chain as well as a strong endogenous lipophilic antioxidant (Turunen et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of antibody production by the addition of Coenzyme-Q10

et al. 2011

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Recently, there has been a growing demand for therapeutic monoclonal antibodies (MAbs) on the global market. Because therapeutic MAbs are more expensive than low-molecular-weight drugs, there have been strong demands to lower their production costs. Therefore, efficient methods to minimize the cost of goods are currently active areas of research. We have screened several enhancers of specific MAb production rate (SPR) using a YB2/0 cell line and found that coenzyme-Q(10) (CoQ(10)) is a promising enhancer candidate. CoQ(10) is well known as a strong antioxidant in the respiratory chain and is used for healthcare and other applications. Because CoQ(10) is negligibly water soluble, most studies are limited by low concentrations. We added CoQ(10) to a culture medium as dispersed nanoparticles at several concentrations (Q-Media) and conducted a fed-batch culture. Although the Q-Media had no effect on cumulative viable cell density, it enhanced SPR by 29%. In addition, the Q-Media had no effect on the binding or cytotoxic activity of MAbs. Q-Media also enhanced SPR with CHO and NS0 cell lines by 30%. These observations suggest that CoQ(10) serves as a powerful aid in the production of MAbs by enhancing SPR without changing the characteristics of cell growth, or adversely affecting the quality or biological activity of MAbs.

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Section: Introductionmentioning

confidence: 99%

Enhancement of antibody production by the addition of Coenzyme-Q10

et al. 2011

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“…It has potent antioxidant and cell membrane stabilizing effects and has also been used as a protective agent in acute cardiac ischemic syndromes, breast cancer, hepatic ischemia reperfusion injury, diabetes, and atherosclerosis [2 -8]. CoQ 10 is currently sold as a dietary supplement in the United States, with a majority of these products being derived from the fermentation of carbohydrates or tobacco leaf extracts [9,10]. Since CoQ 10 can be used as a food supplement or as an adjunctive therapy in many kinds of diseases, it is very important to be able to determine the content of CoQ 10 .…”

Section: Introductionmentioning

confidence: 99%

A rapid and sensitive LC-MS/MS method for determination of coenzyme Q10 in tobacco (Nicotiana tabacum L.) leaves

Zu¹,

Zhao

et al. 2006

J. Sep. Sci.

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A rapid and sensitive liquid chromatography-tandem mass spectrometry method with multiple reaction monitoring has been proposed for the analysis of coenzyme Q10 in (CoQ10) tobacco leaves. The method used electrospray ionization with detection in positive ion mode. Sample pretreatment involved ultrasonic extraction of fresh tobacco leaves with anhydrous ethanol for 15 min and followed by extraction of the supernatant with hexane. The separation of CoQ10 was performed on a Symmetry Shield RP18 column with a mixture of acetonitrile and isopropanol (8:7, v/v) containing 0.5% formic acid as mobile phase. Quantification of CoQ10 was performed by the standard addition method. The limit of detection and limit of quantitation of CoQ10 were, respectively, 1.2 ng/mL (S/N = 3) and 4.0 ng/mL (S/N = 10). The relative standard deviations of peak area were 0.91% and 1.21% for intra-day and inter-day, respectively. The recoveries of CoQ10 ranged from 98.2 to 99.3% and the corresponding RSDs were less than 2.4%. Analysis took 5 min, making the method suitable for rapid determination of CoQ10 in tobacco leaves. The proposed method has been successfully applied to the analysis of CoQ10 in the leaves from eight varieties of tobacco.

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“…Thus, owing to the increasing demand for CoQ 10 in food products, safety data for CoQ 10 manufactured by each manufacturer is requested by consumers. There are preclinical safety reports on CoQ 10 produced by organic synthesis (Chiba et al, 1972;Ikeda et al, 2005) and by fermentation with yeast (Williams et al, 1999;Kitano et al, 2004 and2006), but there are few reports on CoQ 10 produced with bacteria. This research assessed the safety of CoQ 10 manufactured with non-pathogenic bacteria in a subchronic toxicity study in rats.…”

Section: Introductionmentioning

confidence: 99%

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

Honda¹,

Tominaga²,

Oshikata³

et al. 2007

J. Toxicol. Sci.

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-As part of a safety evaluation of Coenzyme Q 10 , a subchronic toxicology study was conducted. Coenzyme Q 10 was repeatedly administered orally to male and female Crl:CD(SD) rats at daily dose levels of 300, 600 and 1200 mg/kg for 13 weeks. Neither death nor any toxicological signs were observed in any group during the administration period. No change related to the test substance administered was observed in any group with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights or histopathology. Based on these results, the nonobserved-adverse-effect level (NOAEL) of Coenzyme Q 10 was considered to be 1200 mg/kg/day for male and female rats under these study conditions.

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28-Day repeated dose toxicity study of dried microorganism in rats

Cited by 10 publications

References 6 publications

Enhancement of antibody production by the addition of Coenzyme-Q10

Enhancement of antibody production by the addition of Coenzyme-Q10

A rapid and sensitive LC-MS/MS method for determination of coenzyme Q10 in tobacco (Nicotiana tabacum L.) leaves

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

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