Detection of fenoldopam-induced arteritis in rats using ex vivo / in vivo MRI

Yuta Fujii; Yuka Yoshino; Kazuhiro Chihara; Aya Nakae; Jun-Ichiro Enmi; Yoshichika Yoshioka; Izuru Miyawaki

doi:10.1016/j.toxrep.2022.07.012

Detection of fenoldopam-induced arteritis in rats using ex vivo / in vivo MRI

Toxicol Rep. 2022 Jul 28:9:1595-1602. doi: 10.1016/j.toxrep.2022.07.012. eCollection 2022.

Authors

Yuta Fujii^{1

2}, Yuka Yoshino^{1

2}, Kazuhiro Chihara¹, Aya Nakae^{2

3}, Jun-Ichiro Enmi^{2

3}, Yoshichika Yoshioka^{2

3}, Izuru Miyawaki¹

Affiliations

¹ Preclinical Research Unit, Sumitomo Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
² Graduate school of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
³ Center for Information and Neural Networks (CiNet), Osaka University and National Institute of Information and Communications Technology (NICT), 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan.

Abstract

A method capable of identifying drug-induced arteritis is highly desirable because no specific and sensitive biomarkers have yet been defined. Although magnetic resonance imaging (MRI) may be used to find a biomarker candidate for drug-induced arteritis, there are no reports on the evaluation of drug-induced arteritis by MRI. The present study was conducted to clarify whether Fenoldopam mesylate (FM)-induced arteritis in rats can be detected by MRI. FM, a dopamine (D1 receptor) agonist, is known to induce arteritis in rats. FM was administered subcutaneously to each rat once daily for 2 days at a dose of 100 mg/kg/day. These arteries were examined with ex vivo high-resolution MRI or postmortem MRI after euthanasia. These arteries were also examined using in vivo MRI on the day after final dosing or 3 days after administration of the final dose. These arteries were examined histopathologically in all experiments. The ex vivo MRI showed low-intensity areas and a high signal intensity region around the artery, and these findings were considered to be erythrocytes infiltrating the arterial wall and perivascular edema, respectively. In the in vivo study, the MRI of the FM-administered group showed a high signal intensity region around the artery. The perivascular edema observed histopathologically was recognized as a high signal intensity region around the artery on the image of MRI. In conclusion, detection of the high signal intensity region around the artery by MRI is considered to be a useful method for identifying arteritis. Although further investigation is needed to be a reliable biomarker, it is suggested that it could be a biomarker candidate.

Keywords: Arteritis; Biomarker; Drug; FA, flip angle; FDA, US Food and Drug Administration; FLASH, fast low-angle shot; FM, fenoldopam mesylate; FOV, field of view; Fenoldopam mesylate; HE, hematoxylin and eosin; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; Magnetic resonance imaging; Perivascular edema; RARE, rapid acquisition with relaxation enhancement; TE, echo time; TR, repetition time.