Effect of pirfenidone on the development of pellagra-related nausea in mice

Kuronuma, Koji; Susai, Natsumi; Ishikawa, Tatsuru; Kuroita, Tomohiro; Yoshioka, Takeshi

doi:10.1183/13993003.congress-2021.pa3278

Cited by 2 publications

(3 citation statements)

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“…Furthermore, some phenotypes of pirfenidone-related adverse effects, such as photosensitivity and nausea, appear to resemble those of pellagra. Currently, we are investigating whether these phenotypes are pellagra-like using our model mice [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the gut microbiome to validate a mouse model of pellagra

Susai

Kuroita

Kuronuma

et al. 2022

Bioscience of Microbiota, Food and Health

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Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of this model is unclear. In this study, we found that the gut microbiota, which is thought to be a source of niacin, played an important role in the development of pellagra-related nausea in germ-free mice. We also investigated the gut microbiome. We compared urinary niacin metabolite levels and the dermal response between mice fed a normal diet and those fed a low-niacin diet to investigate the putative trigger of pellagra. Epoxyeicosatrienoic and hydroxyeicosatetraenoic acid levels were higher in mice fed a low-niacin diet compared with those fed a normal diet. Furthermore, histological studies indicated a dermatological response to the low-niacin diet. Interestingly, higher levels of oxidised fatty acids in response to the germ-free state were also observed. These findings indicate successful establishment of our newly established mouse model of pellagra via the gut microbiota.We believe that this model could enable the discovery of the putative cause of pellagra and phenotypes of pellagra that have not been recognised yet. INTRODUCTIONCPellagra is a clinical syndrome characterised by dermatitis, diarrhoea, dementia, and

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Section: Discussionmentioning

confidence: 99%

Analysis of the gut microbiome to validate a mouse model of pellagra

Susai

Kuroita

Kuronuma

et al. 2022

Bioscience of Microbiota, Food and Health

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“…We previously reported that PFD caused pellagra-related nausea in mice fed a low-niacin diet, but not in those fed a normal diet [ 17 ]. Furthermore, the gut microbiota plays a major role in the development of pellagra-related nausea in mice [ 6 ].…”

Section: Resultsmentioning

confidence: 99%

“…The urinary ratio of NAM/MNA in mice treated with or without PFD was investigated to evaluate whether nausea caused by PFD was similar to that caused by pellagra. This is because abnormal niacin metabolism occurs in pellagra [ 17 , 18 ], and this urinary ratio may represent a suitable biomarker for pellagra [ 6 , 19 ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Protective effect of <i>Bifidobacterium longum</i> BB536 against nausea caused by pirfenidone in a mouse model of pellagra

Kuronuma

Susai

Kuroita

et al. 2023

Bioscience of Microbiota, Food and Health

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Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of Bifidobacterium longum BB536 on pellagra-related nausea caused by pirfenidone in our mouse model. Our pharmacological data indicated that pirfenidone (PFD) causes modulation of the gut microbiota profile, which appeared to play an important role in the development of pellagra-related nausea.A gut microbiota-mediated protective effect of Bifidobacterium longum BB536 against nausea caused by PFD was also identified. Finally, the urinary ratio of nicotinamide/Nmethylnicotinamide was shown to be a biomarker of pellagra-like adverse effects induced by PFD, and it may contribute to the prevention of these effects in patients with idiopathic pulmonary fibrosis.

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Effect of pirfenidone on the development of pellagra-related nausea in mice

Cited by 2 publications

References 0 publications

Analysis of the gut microbiome to validate a mouse model of pellagra

Analysis of the gut microbiome to validate a mouse model of pellagra

Protective effect of <i>Bifidobacterium longum</i> BB536 against nausea caused by pirfenidone in a mouse model of pellagra

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