Research Article
Volume 17 Issue 5 - 2022
Evaluation of Teratogenicity of Pyrroloquinoline Quinone (PQQ) Disodium Salt
Albert W Lee1, Iris L Case1, Zhijia Ding2, Dong Shao3, Xiaoping Zhang3, Jing 3 and Wan Zhang3*
1AceOne RS, Inc., Clarksville, Maryland, USA
2WuXi AppTec (Suzhou) Co., Ltd., People’s Republic of China
3Zhejiang Medicine Co., Ltd., Xinchang, People’s Republic of China
*Corresponding Author: Wan Zhang, Zhejiang Medicine Co., Ltd., Xinchang, Zhejiang Province, People’s Republic of China.
Received: March 23, 2022; Published: April 22, 2022




Abstract

The objective of this study was to evaluate whether Pyrroloquinoline Quinone (PQQ) disodium salt prepared by fermentation using Methylobacterium Methylophilus methylotrophus NCIB 10515 has teratogenic effects on rats when administered orally from Gestation Day 6 (GD6) to GD20 and to characterize the dose response relationship with toxicity. One hundred mated female rats were randomly assigned to 1 of 4 groups (n = 25/group). The control group received vehicle (purified water) by oral gavage once per day, and the test groups received PQQ diluted in purified water by gavage at doses of 50, 100, or 200 mg/kg bw/day daily from GD 6 to GD 20. The rats were observed daily for mortality and clinical signs. Body weight was assessed on GD 0, and every 3rd day after through GD21. Food consumption was assessed on GDs 1-2, 6-7, 9-10, 12-13, 15-16, and 19-20. On GD 21, all animals were necropsied and examined macroscopically. Ovaries and uteri were examined for litter data-those without visible implantation were placed in ammonium sulfide solution to assess whether early resorptions had occurred. Live fetuses were weighed and examined for external abnormalities. Then sex was determined and crown-rump length was measured. About half of each litter’s live fetuses were fixed with modified Davidson’s fixative for soft tissue examination and the remaining fetuses in were stained with Alizarin red solution for skeletal examination. There were no treatment-related changes on clinical or macroscopic observations, litter data, sex ratio, fetal weights, crown-rump length, or fetal structure. No mortality was observed. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) of PQQ disodium salt was considered to be 200 mg/kg bw/day, the highest dose tested, for maternal toxicity and embryo-fetal developmental toxicity.

 

Keywords: Pyrroloquinoline Quinone; PQQ Disodium Salt; Methylophilus methylotrophus NCIB 10515, Teratogenicity; Prenatal Development Toxicity

References

  1. Salisbury SA., et al. “A novel coenzyme from bacterial primary alcohol dehydrogenases”. Nature5725 (1979): 843-844.
  2. Kumazawa T., et al. “Levels of pyrroloquinoline quinone in various foods”. Biochemical Journal 2 (1992): 331-333.
  3. Misra HS., et al. “Pyrroloquinoline-quinone and its versatile roles in biological processes”. Journal of Biosciences 2 (2012): 313-325.
  4. Noji N., et al. “Simple and sensitive method for pyrroloquinoline quinone (PQQ) analysis in various foods using liquid chromatography/electrospray-ionization tandem mass spectrometry”. Journal of Agricultural and Food Chemistry 18 (2007): 7258-7263.
  5. Rucker R., et al. “Potential physiological importance of pyrroloquinoline quinone”. Alternative Medicine Review 3 (2009): 268-277.
  6. Liang C., et al. “A subchronic oral toxicity study on pyrroloquinoline quinine (PQQ) disodium salt in rats”. Food and Chemical Toxicology 75 (2015): 146-150.
  7. Nakano M., et al. “Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats”. Regulatory Toxicology and Pharmacology1 (2014): 107-121.
  8. China Center for Disease Control and Prevention, National Center for Food Safety Risk Assessment. PQQ Toxicology Test Report #2. Unpublished study cited in US FDA 2016 (GRN 625) (2012).
  9. US FDA. GRN 625 (2016).
  10. Steinberg F., et al. “Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets”. Experimental Biology and Medicine 2 (2003): 160-166.
  11. Steinberg FM., et al. “Dietary pyrroloquinoline quinone: growth and immune response in BALB/c mice”. Journal of Nutrition5 (1994): 744-753.
  12. Zhang B., et al. “Effect of pyrroloquinoline quinone disodium in female rats during gestating and lactating on reproductive performance and the intestinal barrier functions in the progeny”. British Journal of Nutrition 7 (2019): 818-830.
Citation: Wan Zhang., et al. “Evaluation of Teratogenicity of Pyrroloquinoline Quinone (PQQ) Disodium Salt”. EC Nutrition 17.5 (2022): 01-09.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


May Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the May issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before June 07, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.