Both Plasma Lysophosphatidic Acid and Serum Autotaxin Levels are Increased in Chronic Hepatitis C

Abstract

The serum ATX activity and plasma LPA level are increased in chronic hepatitis C in association with liver fibrosis. Our study may provide the first evidence showing a significant increase of both ATX and LPA in the blood under a specific disease.

LPA receptor signaling: pharmacology, physiology, and pathophysiology

“…However, there is a growing range of recognized chemical forms of LPA in various biological systems (31,32) that have been observed in concentrations spanning low nanomolar to micromolar levels. LPA concentrations in blood can range from 0.1 M in plasma and up to 10 M in serum, which is well over the apparent nanomolar K d of LPA [1][2][3][4][5][6] (23,(33)(34)(35) (36)(37)(38). Aside from blood, LPA has been quantifi ed in a variety of species, tissues, and fl uids, including neural tissue, cerebrospinal fl uid (CSF), seminal fl uid, urine, saliva, and aqueous humor (7,36,(39)(40)(41)(42)(43)(44)(45) (Table 1).…”

“…are increased following hepatitis C-induced liver fi brosis, presumably through induction of stellate cell and hepatocyte proliferation (35,249), which are the main contributors to extracellular matrix accumulation in the liver (250).…”

Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets

“…Finally, the significance of the plasma or serum ATX levels in cancer patients has been reported in patients with follicular lymphoma, where serum ATX levels proved to be significantly higher than those in healthy subjects, to correlate with plasma LPA levels and to change according to patient clinical course (Masuda et al, 2008). Additional studies have reported an impressive and specific increase in serum ATX activity and plasma LPA in patients with chronic hepatitis C (Watanabe et al, 2007) and pancreatic cancer (Nakai et al, 2011). In the last 20 years several studies have considered the potential role of the ATX/LPA axis in ovarian cancer.…”

Pathophysiological relevance of neutrophils in acetaminophen hepatotoxicity

“…We read with interest the recent article by Marques et al 1 on the release of damage-associated molecular patterns during acetaminophen (APAP) hepatotoxicity in mice and humans. We were pleased to learn that the authors were able to confirm certain previously published data, especially the release of mitochondrial products in human pathophysiology, which we recently reported.…”

“…2 However, we have concerns regarding the conclusion that neutrophils are aggravating APAP-induced hepatotoxicity based on the data presented. 1 Pretreatment with the neutropenia-inducing antibody Gr-1 induces a preconditioning effect with up-regulation of numerous genes, many of which are highly protective against APAP hepatotoxicity. 3 Thus, no reliable conclusions regarding the involvement of neutrophils can be obtained from these experiments.…”