Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy

Perry, Tracy Ann; Weerasuriya, Ananda; Mouton, Peter R.; Holloway, Harold W.; Greig, Nigel H.

doi:10.1016/j.expneurol.2004.07.013

Cited by 58 publications

(52 citation statements)

References 32 publications

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“…However, both the cause of PN toxicity and the exact role of YggS in vitamin B 6 homeostasis remain to be elucidated. PN neurotoxicity has been reported previously in mammals (rats, dogs and humans) (Schaeppi & Krinke, 1982;Albin et al, 1987;Perry et al, 2004) and we show also here that PN is toxic when PdxK is overproduced in E. coli, also suggestive of PNP toxicity (Fig. S3B).…”

Section: Discussionsupporting

confidence: 62%

Evidence that COG0325 proteins are involved in PLP homeostasis

et al. 2016

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Pyridoxal 59-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 59-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.

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Section: Discussionsupporting

confidence: 62%

Evidence that COG0325 proteins are involved in PLP homeostasis

et al. 2016

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“…Long-term administration of high doses has been correlated with neuropathy; however, the mechanism of action has not been fully uncovered and has yielded disparate results (Perry et al, 2004). What has been shown is that vitamin B 6 intoxication manifests primarily as structural and functional changes in large sensory neurons, with the secondary effects being on axonal processes within the dorsal root ganglia and the trigeminal nerve (Parry and Bredesen, 1985;Xu et al, 1989).…”

Section: Vitamin B 6 and Traumatic Brain Injurymentioning

confidence: 99%

Pyridoxine Administration Improves Behavioral and Anatomical Outcome after Unilateral Contusion Injury in the Rat

Kuypers

Hoane²

2010

Journal of Neurotrauma

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The purpose of this project was to evaluate the preclinical efficacy of pyridoxine, or vitamin B 6 . Rats received a 3.0 mm unilateral controlled cortical impact (CCI) injury of the sensorimotor cortex or sham surgery. Treatment with vitamin B 6 (600 or 300 mg/kg IP) or vehicle was administered at 30 min and 24 h post-CCI. Somatosensory dysfunction was evaluated with the vibrissae-forelimb placing and bilateral tactile adhesive removal tests. Sensorimotor dysfunction was evaluated with the locomotor placing and the forelimb asymmetry tests. On the forelimb asymmetry test both treatment groups displayed no asymmetry bias on any of the testing days post-CCI and were statistically no different than the shams. Both vitamin B 6 groups displayed a significant improvement in behavioral performance on the locomotor placing test compared to the vehicle-treated group. Administration of 600 mg/kg also significantly reduced tactile adhesive removal latencies on days 2, 4, 6, and 12 post-CCI. Both treatment groups were improved in their rate of recovery post-CCI on the vibrissae-forelimb placing test, but only the recovery seen in the 600-mg/kg group was significantly improved compared to vehicle. Finally, the 600-mg/kg dose resulted in significant cortical sparing compared to the vehicle-treated group. In general, the effects of vitamin B 6 on recovery of function were dose-dependent, with the 600-mg/kg dose consistently showing greater recovery than the 300-mg/kg dose. More experimental analyses are warranted to evaluate the potential preclinical efficacy and mechanistic action of vitamin B 6 .

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“…Studies on laboratory rodents published after the SCF assessment indicate that dose levels higher than 100 mg/kg bw are required to elicit neurotoxicity (Arkaravichien et al, 2003;Perry et al, 2004;Hong et al, 2009). Some experimental studies indicate impairment of renal function and/or imbalances with other water-soluble vitamins (e.g.…”

Section: Toxicological Studiesmentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of vitamin B6 (pyridoxine hydrochloride) as a feed additive for all animal species

2011

EFS2

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Pyridoxine hydrochloride is a form of vitamin B 6 , an essential micronutrient. Oral administration routes of pyridoxine hydrochloride via feed or water are considered as bioequivalent. Pyridoxine hydrochloride is considered to be safe for all animal species at the commercial use levels. The FEEDAP Panel concludes that the use of pyridoxine hydrochloride as a nutritional additive does not give rise to concern for consumers. Pyridoxine hydrochloride is not an irritant to skin and eyes; it is not a skin sensitizer. The Panel notes that pyridoxine hydrochloride may cause photosensitisation. The pyridoxine hydrochloride considered in this opinion has a high dusting potential. A calculation of exposure by inhalation for persons handling the substance in a premixture factory resulted in an intake of 3.1 mg/person/day. Together with exposure by food sources, total exposure would not exceed 60 % of the UL. In the absence of inhalation toxicity studies, adverse effects in the respiratory tract cannot be fully excluded. Pyridoxine occurs widely in nature (in most plant feed materials). Its use in animal nutrition is not expected to substantially increase the concentration in the environment. Therefore, a risk for the environment resulting from the use of pyridoxine in animal nutrition is not foreseen. Due to the long history of use and its established nutritional role in domestic animals, pyridoxine hydrochloride is regarded as an effective source of vitamin B 6 . © European Food SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of pyridoxine hydrochloride, supplied via feed or water, as a feed additive for all animal species.Pyridoxine hydrochloride is a form of vitamin B 6 , an essential micronutrient, it occurs in the body as pyridoxal 5"-phosphate which serves as a coenzyme in transamination, decarboxylation and desamination reactions. It plays an important role in the metabolism of proteins (amino acids), fatty acids and carbohydrates, and in the synthesis of transmitters. Its major role is in neuroprotection.Oral administration routes of pyridoxine hydrochloride via feed or water are considered as bioequivalent.Pyridoxine hydrochloride is considered to be safe for all animal species at the commercial use levels.The FEEDAP Panel concludes that the use of pyridoxine hydrochloride as a nutritional additive does not give rise to concern for consumers.Pyridoxine hydrochloride is not an irritant to skin and eyes; it is not a skin sensitiser. The FEEDAP Panel notes that pyridoxine hydrochloride may cause photosensitisation. The pyridoxine hydrochloride considered in this opinion has a high dusting potential. A calculation of exposure by inhalation for persons handling the substance in a premixture factory resulted in an intake of 3.1 mg/person/day. Together with exposure by food sources, total exposure would not exceed 60 % of the UL. In the absence of inhalatio...

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Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy

Cited by 58 publications

References 32 publications

Evidence that COG0325 proteins are involved in PLP homeostasis

Evidence that COG0325 proteins are involved in PLP homeostasis

Pyridoxine Administration Improves Behavioral and Anatomical Outcome after Unilateral Contusion Injury in the Rat

Scientific Opinion on the safety and efficacy of vitamin B6 (pyridoxine hydrochloride) as a feed additive for all animal species

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