2. Academic Validation
  3. Aminoglutethimide-induced lysosomal changes in adrenal gland in mice

Aminoglutethimide-induced lysosomal changes in adrenal gland in mice

  • Exp Toxicol Pathol. 2017 Sep 5;69(7):424-429. doi: 10.1016/j.etp.2017.04.004.
Mayu Mutsuga 1,  Yoshiji Asaoka 1,  Naoko Imura 1,  Tomoya Miyoshi 1,  Yuko Togashi 2
Affiliations

Affiliations

  • 1 Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • 2 Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: [email protected].
PMID: 28410883 DOI: 10.1016/j.etp.2017.04.004
Abstract

Aminoglutethimide is a steroidogenesis inhibitor and inhibits a Cholesterol side-chain cleavage enzyme (CYP11A1) that converts Cholesterol to pregnenolone in mitochondria. We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes and single cell necrosis were found in zona fasciculata cells in AG-treated mice. Some vacuoles were positive for adipophilin, whereas Others were positive for lysosome-associated membrane protein-2 on immunohistochemical staining, indicating they were enlarged lipid droplets and lysosomes, respectively. Electron microscopy revealed enlarged lysosomes containing damaged mitochondria and lamellar bodies in zona fasciculata cells, and they were considered to reflect the intracellular protein degradation processes, Mitophagy and lipophagy. From these results, we showed that AG induces excessive lipid accumulation and mitochondrial damage in zona fasciculata cells, which leads to an accelerated lysosomal degradation in mice.

Keywords

Adrenal toxicity; Aminoglutethimide; Autophagy; Mouse.

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