- 著者
- Shinya TAKENOUCHI Yui KOBAYASHI Tatsuya SHINOZAKI Koji KOBAYASHI Tatsuro NAKAMURA Tomohiro YONEZAWA Takahisa MURATA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.22-0049, (Released:2022-04-05)
Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are metabolized into various lipid mediators. Lipid mediators such as prostaglandins (PGs) modulate inflammation and many of them are excreted into the urine. Thus, the investigation of the urinary lipid profile may reveal pathogenesis and help diagnosis of FIC. We collected urine samples from five FIC cats by spontaneous urination and analyzed 158 types of lipid mediators in urines using liquid chromatography-mass spectrometry. The urinary levels of PUFAs were higher in FIC compared to those of the healthy group. The excretions of a major inflammatory mediator, PGD2, were less in FIC. Other well-known inflammatory mediators such as PGE2, PGI2, and their metabolites did not show a difference. In contrast, the levels of PGF2α and its 2 metabolites and PGF3α were higher in FIC. These results may provide new insights into the future management of cat FIC.
- 著者
- Shinya TAKENOUCHI Yui KOBAYASHI Tatsuya SHINOZAKI Koji KOBAYASHI Tatsuro NAKAMURA Tomohiro YONEZAWA Takahisa MURATA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- vol.84, no.5, pp.689-693, 2022 (Released:2022-05-17)
- 参考文献数
- 37
Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are metabolized into various lipid mediators. Lipid mediators such as prostaglandins (PGs) modulate inflammation and many of them are excreted into the urine. Thus, the investigation of the urinary lipid profile may reveal pathogenesis and help diagnosis of FIC. We collected urine samples from five FIC cats by spontaneous urination and analyzed 158 types of lipid mediators in urines using liquid chromatography-mass spectrometry. The urinary levels of PUFAs were higher in FIC compared to those of the healthy group. The excretions of a major inflammatory mediator, PGD2, were less in FIC. Other well-known inflammatory mediators such as PGE2, PGI2, and their metabolites did not show a difference. In contrast, the levels of PGF2α and its 2 metabolites and PGF3α were higher in FIC. These results may provide new insights into the future management of cat FIC.
- 著者
- Yui KOBAYASHI Tatsuro NAKAMURA Tomohiro YONEZAWA Koji KOBAYASHI Takahisa MURATA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.21-0433, (Released:2021-11-05)
- 被引用文献数
- 1
Bacterial cystitis is one of the feline lower urinary tract diseases (FLUTDs). Polyunsaturated fatty acids, such as arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are oxidized into various lipid mediators that modulate inflammation. Since the profile of lipid metabolites excreted in urine is useful for assessing inflammatory body conditions, we analyzed 126 types of urinary lipid metabolites in cats with bacterial cystitis. Using LC-MS/MS, we found that the levels of 11 metabolites were higher in the urine of cystitis cats than in the urine of healthy cats. In detail, the urinary levels of ARA, EPA, and DHA and eight of their metabolites were increased in cystitis cats. Focusing on the lipid oxidation pathway, the urinary levels of four cyclooxygenase-, three lipoxygenase-, and one cytochrome p450-dependent oxidated metabolites were increased in bacterial cystitis. These urinary lipid profiles can provide some insight into the pathology and future diagnosis of bacterial cystitis.
- 著者
- Tomonori Miura Yusuke Kamiya Shiori Hina Yui Kobayashi Norie Murayama Makiko Shimizu Hiroshi Yamazaki
- 出版者
- The Japanese Society of Toxicology
- 雑誌
- The Journal of Toxicological Sciences (ISSN:03881350)
- 巻号頁・発行日
- vol.45, no.11, pp.695-700, 2020 (Released:2020-11-02)
- 参考文献数
- 26
- 被引用文献数
- 1 9
Coumarin is a dietary-derived substance that is extensively metabolized by human liver to excretable 7-hydroxycoumarin. Although coumarin under daily dietary consumption is generally regarded as nontoxic, the substance is of toxicological and clinical interest because of its potential association with hepatotoxicity, which is especially evident in rats. In this study, the pharmacokinetics of coumarin were modeled after virtual oral administration in humans. The adjusted monitoring equivalents of coumarin, along with the biotransformation of coumarin to o-hydroxyphenylacetic acid (via 3,4-epoxidation) based on reported plasma concentrations from rat studies, were scaled to human coumarin equivalents using known species allometric scaling factors. Using rat and human liver preparations, data on the rapid in vitro metabolic clearance for humans (~50-fold faster than in rats) were obtained for in vitro–in vivo extrapolation. For human physiologically based pharmacokinetic (PBPK) modeling, the metabolic ratios to o-hydroxyphenylacetic acid and 7-hydroxycoumarin were set at minor (0.1) and major (0.9) levels for the total disappearance of coumarin. The resulting modeled plasma concentration curves in humans generated by simple PBPK models were consistent with reported simulated coumarin maximum concentrations. These results provide basic information to simulate plasma levels of coumarin and its primary metabolite 7-hydroxycoumarin or its secondary activated metabolite o-hydroxyphenylacetic acid (via 3,4-epoxidation) resulting from dietary foodstuff consumption. Under the current assumptions, little toxicological impact of coumarin was evident in humans, thereby indicating the usefulness of forward dosimetry using PBPK modeling for human risk assessment.
- 著者
- Yui KOBAYASHI Tatsuro NAKAMURA Koji KOBAYASHI Takahisa MURATA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.20-0238, (Released:2020-06-05)
- 被引用文献数
- 5
Polyunsaturated fatty acids including arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are converted to lipid mediators by oxidation. Unlike other mammals, cats cannot synthesize AA. Since their lipid metabolic features remain unknown, we qualitatively analyzed 118 types of urinary lipid metabolites in healthy neutered cats. Using LC-MS, we found 26 lipid metabolites in urines of all individuals. In detail, 20 AA-, 5 EPA- and 1 DHA-derived lipid mediators were detected. Focusing on oxidative pathway, 17 cyclooxygenase-metabolites and 5 metabolites produced by non-enzymatic pathway were detected. Of interest, few lipoxygenase- or cytochrome P450-metabolites were excreted. Thus, AA-derived cyclooxygenase-metabolites mainly composed the urinary lipid metabolites in cats.