Comparative study of hydrolytic metabolism of dimethyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate by microsomes of various rat tissues

Ozaki, Hitomi; Sugihara, Kazumi; Watanabe, Yoko; Moriguchi, Kyoko; Uramaru, Naoto; Sone, Tomomichi; Ohta, Shigeru; Kawa, Shigeyuki

doi:10.1016/j.fct.2016.12.019

Cited by 32 publications

(11 citation statements)

References 54 publications

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“…The significant reduction in the villus height and the V / C ratio in the duodenum after exposure to the high concentration of DBP indicated that DBP has an adverse effect on the absorptive capacity of the jejunum. Ozaki et al (2017) examined the hydrolytic metabolism of DBP using rat tissue microsomes and found that small intestinal microsomes exhibit higher activity toward long-side-chain phthalates. Therefore, the present findings that DBP promotes the growth of villi in the duodenum and has a damaging effect on the absorptive capacity of the jejunum suggest that DBP can cause tissue-specific effects in the intestine.…”

Section: Discussionmentioning

confidence: 99%

Short-term toxicity of dibutyl phthalate to mice intestinal tissue

Wang

et al. 2018

Toxicol Ind Health

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The objective of this study was to investigate changes in intestinal histopathology and expression of heat-shock proteins (HSPs) in the small intestinal tissue of mouse after acute exposure to dibutyl phthalate (DBP). Forty-eight 60-day-old Institute of Cancer Research (ICR) mice were administered DBP by gavage once a day for 10 days. The mice were divided into three groups of 16 mice each: the high-dose group was administered 500 mg/kg body weight (BW) DBP; the low-dose group was administered 50 mg/kg BW; and the control group was not administered DBP. Significant increases in the uterine index, ovary index, and testicular index were observed in the DBP-exposed groups compared to those in the control group. Villus height and V/ C ratio significantly increased ( p < 0.05) in the duodenum and decreased ( p < 0.05) in the jejunum after the administration of DBP. The goblet cell number decreased in both the duodenum and the jejunum of mice exposed to DBP ( p < 0.05) compared to the number in the control group mice. Damage to the structure of the small intestine was accompanied by a marked increase in HSP27 expression and a decrease in the expression of HSP70 and HSP90 in both high-dose and low-dose groups. These results indicate that elevated HSP27 levels in the duodenum and jejunum may be important markers for acute DBP exposure and that HSP27 may act as a protective protein involved in intestinal mucosa repair.

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Section: Discussionmentioning

confidence: 99%

Short-term toxicity of dibutyl phthalate to mice intestinal tissue

Wang

et al. 2018

Toxicol Ind Health

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“…This could be explained by their binding to the allosteric site of the enzyme that would cause a conformation change as reported for some BPA analogues (Zhu, 2017). Moreover, di-phthalates are metabolised to their mono-derivatives by the hydrolytic action of CEs in mammalian systems (Ozaki et al, 2017), and some of these metabolites possess higher endocrine disruption potential (Chauvigne et al, 2011) and cause severer oxidative stress conditions (Pérez-Albadalejo et al, 2020) than the parent compounds.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

“…However, the authors were unable to relate if the toxicity was due to the polymer itself or to its additives. Since phthalates are metabolised by CEs (Ozaki et al, 2017) and the fact that some of their metabolites can be more toxic than the parental compound (e.g DEHP to MEHP), the study of the in vivo toxicity assessment in marine invertebrates requires investigation. Nevertheless, a relatively easy and fast first in vitro screening using hepatic homogenates of marine species based on mammalian protocols could be an interesting and more immediate approach.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

The use of an in vitro approach to assess marine invertebrate carboxylesterase responses to chemicals of environmental concern

Solé

Freitas

Rivera‐Ingraham

2021

Environmental Toxicology and Pharmacology

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“…Induction of MNGs by BBP could also be predicted based on its metabolism. The active metabolite responsible for phthalate toxicity is the monoester produced by cleavage of a single side chain, predominantly by intestinal lipase (Ozaki et al, 2017). The active metabolites of DBP and DEHP are MBP and MEHP, respectively.…”

Section: Discussionmentioning

confidence: 99%

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells

et al. 2018

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In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats. The anti-androgenic effects of phthalates have been more thoroughly quantified than testicular pathology due to the significant time requirement associated with manual counting of MNGs on histological sections. An automated counting method was developed in ImageJ to quantify MNGs in digital images of hematoxylin-stained rat fetal testis tissue sections. Timed pregnant Sprague Dawley rats were exposed by daily oral gavage from gestation day 17 to 21 with one of eight phthalate test compounds or corn oil vehicle. Both the manual counting method and the automated image analysis method identified di-n-butyl phthalate, butyl benzyl phthalate, dipentyl phthalate, and di-(2-ethylhexyl) phthalate as positive for induction of MNGs. Dimethyl phthalate, diethyl phthalate, the brominated phthalate di-(2-ethylhexyl) tetrabromophthalate, and dioctyl terephthalate were negative. The correlation between automated and manual scoring metrics was high (r = 0.923). Results of MNG analysis were consistent with these compounds' anti-androgenic activities, which were confirmed in an ex vivo testosterone production assay. In conclusion, we have developed a reliable image analysis method that can be used to facilitate dose-response studies for the reproducible induction of MNGs by in utero phthalate exposure.

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Comparative study of hydrolytic metabolism of dimethyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate by microsomes of various rat tissues

Cited by 32 publications

References 54 publications

Short-term toxicity of dibutyl phthalate to mice intestinal tissue

Short-term toxicity of dibutyl phthalate to mice intestinal tissue

The use of an in vitro approach to assess marine invertebrate carboxylesterase responses to chemicals of environmental concern

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells

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