Bile acids regulate cysteine catabolism and glutathione regeneration to modulate hepatic sensitivity to oxidative injury.

Bile acids are signaling molecules that critically control hepatocellular function. Disrupted bile acid homeostasis may be implicated in the pathogenesis of chronic liver diseases. Glutathione is an important antioxidant that protects the liver against oxidative injury. Various forms of liver disease share the common characteristics of reduced cellular glutathione and elevated oxidative stress. This study reports a potentially novel physiological function of bile acids in regulating hepatic sulfur amino acid and glutathione metabolism. We found that bile acids strongly inhibited the cysteine dioxygenase type-1-mediated (CDO1-mediated) cysteine catabolic pathway via a farnesoid X receptor-dependent mechanism. Attenuating this bile acid repressive effect depleted the free cysteine pool and reduced the glutathione concentration in mouse liver. Upon acetaminophen challenge, cholestyramine-fed mice showed impaired hepatic glutathione regeneration capacity and markedly worsened liver injury, which was fully prevented by N-acetylcysteine administration. These effects were recapitulated in CDO1-overexpressing hepatocytes. Findings from this study support the importance of maintaining bile acid homeostasis under physiological and pathophysiological conditions, as altered hepatic bile acid signaling may negatively impact the antioxidant defense mechanism and sensitivity to oxidative injury. Furthermore, this finding provides a possible explanation for the reported mild hepatotoxicity associated with the clinical use of bile acid sequestrants in human patients.

Cribriform adenocarcinoma of the minor salivary gland arising in the tonsil with metastasis to a cervical lymph node: A case report with description of fine needle aspiration cytology.

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is a rare tumor of the head and neck. We report a case of a 70-year-old female who presented with a 4-5-month history of a left neck mass. CT scan of the neck showed a left neck mass just inferior to the angle of the mandible and left tonsillar prominence. Fine-needle aspiration (FNA) of the neck mass showed epithelial groups with focal cribriform architecture. The cells had round to oval nuclei and fine chromatin. The background contained scattered lymphocytes. A preliminary diagnosis of low grade adenocarcinoma with cribriform features metastatic to a lymph node was made. Subsequent biopsy of the tonsil mass showed a tumor with a combination of tubular, solid, and papillary architecture containing round to ovoid nuclei with very fine chromatin, consistent with cribriform adenocarcinoma of the minor salivary gland. Cribriform adenocarcinoma of minor salivary gland has a documented tendency to metastasize to cervical lymph nodes. Since this neoplasm can cytologically and histologically resemble other neoplasms of the head and neck, including polymorphous low-grade adenocarcinoma (PLGA), papillary thyroid carcinoma (PTC), and occasionally adenoid cystic carcinoma, being aware of and familiar with the cytologic features of CAMSG on FNA smears is important for patient management. Diagn. Cytopathol. 2017;45:468-471. © 2017 Wiley Periodicals, Inc.