Morphological Changes of Mitochondria in the Hepatocytes Induced by Administration of a Large Amount of Di (2-ethylhexyl) phthalate (DEHP) to Cynomolgus Monkeys (Macaca fascicularis)

Satake, Shigeru; Tanigawa, Youhei; Maeda, Hiroshi; Kamimura, Yasuhiro; Chihaya, Yutaka; Miyajima, Hiroaki; Goryo, Masanobu; Okada, Kōsuke

doi:10.1293/tox.21.73

Cited by 3 publications

(5 citation statements)

References 6 publications

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“…In the present study and our previous study, 13 peroxisomal proliferation and mitochondrial changes were clearer in females than in males. The changes in both the females and males were slight.…”

Section: Discussionsupporting

confidence: 77%

“…These results suggested that the peroxisome proliferation was subtle. In our previous study, 13 we could not reach a conclusion as to whether or not DEHP induced peroxisome proliferation. We added the biopsy before treatment and a vehicle control and increased the number of animals in the present study.…”

Section: Discussionmentioning

confidence: 65%

“…In our previous study, 13 morphological changes of mitochondria, such as enlargement and lamellar orientation of the cristae along the major axis, were observed in 2 female cynomolgus monkeys whose body weights decreased at ratios of 10.7% or 11.7% at 1,000 mg/kg/day of DEHP, and the possibility that malnutrition could have caused the mitochondrial changes was suggested. In the present study, mitochondrial abnormalities were observed in one female; however, body weight loss was not noted in this animal.…”

Section: Discussionmentioning

confidence: 90%

“…Accordingly, cynomolgus monkeys were not treated with a higher dose of DEHP in these studies. In our previous study, 13 repeated oral treatment of cynomolgus monkeys with a large dose (1,000 or 2,500 mg/kg/day) of DEHP showed a tendency to increase peroxisome proliferation in hepatocytes; however, a small number of animals was used without any corresponding control. Additionally, at 1,000 mg/kg/day of DEHP, body weight deceased by around 10%, and enlargement of the mitochondria with lamellar orientation of the cristae along the major axis was observed in two females.…”

Section: Introductionmentioning

confidence: 98%

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Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

et al. 2010

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To elucidate the effect of a large dose of di (2-ethylhexyl) phthalate (DEHP), a plasticizer and peroxisome proliferator-activated receptor-α (PPARα) agonist, on hepatic peroxisomes, we orally administered 1,000 mg/kg/day, once daily, to 3 male and 4 female cynomolgus monkeys for 28 days consecutively. Light-microscopic and electron microscopic examinations of the liver were carried out in conjunction with measurement of the hepatic fatty acid β-oxidation system (FAOS), carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (CPT) activities, which are peroxisomal and/or mitochondrial enzyme activities. Electron microscopically, enlargement of the mitochondria was observed with lamellar orientation of the cristae along the major axis. Although the number of peroxisomes showed a tendency to increase when compared with those in a biopsied specimen before treatment, no abnormality in morphology was observed. A slight increase in CPT activity was noted at termination. No changes were noted in hepatic FAOS or CAT activity. In conclusion, although repeated oral treatment of cynomolgus monkeys with a large dose of DEHP induced a subtle increase in the numbers of peroxisomes with slight enlargements of the mitochondria, this low-sensitivity response to peroxisome proliferators in cynomolgus monkeys was considered to be closer to the response in humans than that in rodents.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

et al. 2010

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“…It is well known that the administration of some chemicals and a variety of nutritional manipulations induce the appearance of giant mitochondria in experimental animals (Ludatscher and Silbermann 1976; Rohr and Riede 1973; Satake et al 2008; Tandler and Hoppel 1986; Suzuki 1969; Wakabayashi, Asano, and Kawamoto 1979). In humans, giant mitochondria have been reported in a variety of diseases such as steatohepatitis and mitochondrial neurogastrointestinal encephalopathy (Caldwell et al 1999; Perez-Atayde et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Giant Mitochondria in Pancreatic Acinar Cells of Alloxan-Induced Diabetic Rats

Sano¹,

Ozaki²,

Matsuura³

et al. 2010

Toxicol Pathol

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This was a study of the microscopic, ultrastructural, immunohistochemical, and enzyme cytochemical features of giant eosinophilic granules encountered in pancreatic acinar cells of alloxan-induced diabetic rats. Seven male F344 rats with diabetes induced by a single i.v. dose of alloxan were sacrificed after twenty-five weeks of treatment. Histologically, the pancreatic acini were diffusely atrophied, and the islets showed marked atrophy or had disappeared, and giant eosinophilic granules and small vacuoles were observed in almost all acinar cells. The eosinophilic granules showed negative reactions for periodic acid-Schiff (PAS) and acid phosphatase, as well as fat stains such as Nile blue, Oil red O, and Sudan III. Ultrastructurally, the giant eosinophilic granules were huge structures surrounded by a double membrane containing many irregular cristae. A large amount of small lipid droplets was also apparent in the basal area of the acinar cells. Immunohistochemical analysis of prohibitin, a kind of protein located in the mitochondrial inner membrane, was partially positive in the marginal area of some giant eosinophilic granules, but negative for the central area. The enzyme activity for succinic dehydrogenase (SDH), one of the mitochondrial enzymes, showed a localizing pattern similar to that of prohibitin. These findings confirmed that the giant eosinophilic granules in the exocrine pancreas of alloxan-induced diabetic rats were giant mitochondria.

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Food emulsifier glycerin monostearate aggravates phthalates’ testicular toxicity by disrupting tight junctions’ barrier function in rats

Xia

Yang

et al. 2021

Food Quality and Safety

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Objectives This study was aimed to investigate the effect of widely used food emulsifier glycerin monostearate (GM) on testicular toxicity caused by the mixture of three commonly used PEs (MPEs) in rats, and further to explore the underlying mechanism. Materials and Methods Thirty male Sprague-Dawley rats were divided into three groups randomly. Rats were orally treated with 160 mg/kg/d MPEs in MPEs group; Rats were coinstantaneously treated with 160 mg/kg/d MPEs and 200 mg/kg/d GM in MPEs+GM group; Rats were treated with the excipient in control group. The intervention last for 5 weeks. Testis weight, epididymis weight, testicular histopathology and serum testosterone were detected for testicular toxicity evaluation. The testicular ultrastructure, the tight junction proteins zonula occluden (ZO)-1 and claudin were measured for the mechanism exploration. Results The body weight, epididymis, serum testosterone level, and anogenital distance in MPEs+GM group were significantly decreased comparing with control group (P<0.05); Testicular histopathological observation showed that shed spermatids were observed in MPEs+GM group. Ultrastructural observation of testicular cells showed that the cristae number was decreased in some mitochondrion in MPEs group, whereas the cristae was fused and disappeared in most mitochondrion in MPEs+GM group. The tight junctions were broken in MPEs+GM group, meanwhile, the expression of ZO-1 and claudin were altered in MPEs+GM group (P<0.01). Conclusions The results from this study indicated that GM aggravated MPEs’ testicular toxicity, which might relate to the injured mitochondrion and damaged tight junctions in testicular tissue.

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Morphological Changes of Mitochondria in the Hepatocytes Induced by Administration of a Large Amount of Di (2-ethylhexyl) phthalate (DEHP) to Cynomolgus Monkeys (Macaca fascicularis)

Cited by 3 publications

References 6 publications

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

Giant Mitochondria in Pancreatic Acinar Cells of Alloxan-Induced Diabetic Rats

Food emulsifier glycerin monostearate aggravates phthalates’ testicular toxicity by disrupting tight junctions’ barrier function in rats

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