Effect of histidine on autotaxin activity in experimentally induced liver fibrosis

Abstract

The aim of this study was to explain whether serum autotaxin (ATX) activity might be a target for regulation of liver fibrosis and to evaluate the hepatoprotective and antifibrotic effects of histidine in thioacetamide (TAA)-induced liver fibrosis in rats. This study was carried out on 100 Wistar Albino rats, classified into five groups, each containing 20 rats: Group I (control group), Group II: rats were given histidine intraperitoneally, Group III: rats were injected intraperitoneally with TAA, Group IV: rats were injected with L-histidine together with TAA, and Group V: rats were injected with TAA for 1 month then treated with intraperitoneal injection of L-histidine for another month. At the end of experiment, blood and liver were collected for determination of some liver enzymes, plasma total antioxidant capacity (TAC), serum ATX activity, and liver tissue hydroxyproline. Thioacetamide treatment caused significant increases in liver enzymes, ATX activities, and liver hydroxyproline, but a significant decrease in plasma's TAC. Upon treatment with histidine, a significant decrease in liver enzymes, ATX activities, and liver hydroxyproline was observed with a significant increase in plasma TAC in Group IV and a significant decrease in Group V. Histidine as an antioxidant has a protective effect on TAA-induced liver fibrosis; it is beneficial in rats not only by inhibition of collagen synthesis and increasing TAC but also by inhibition of ATX activities thus reducing its capacity to produce lysophosphatidic acid, which has a role in liver fibrosis. C 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:143-150, 2011; View this article online at wileyonlinelibrary.com.

Oral administration of vitamin C and histidine attenuate cyclophosphamide-induced hemorrhagic cystitis in rats

“…injection of histidine reversed the decreased TAC. [20] Oral supplementation of L-histidinol, a structural analog of the essential amino acid L-histidine, strongly ameliorated the severity of renal disfunction and reduced the MDA accumulation induced by ifosfamide in rats. [21] Histidine significantly decreased MDA formation, increased GSH content and enhanced CAT and GPx activities when used after chronic alcoholic liver injury induced by ethanol in rats.…”

Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions

“…l ‐histidine inhibits ATX activity in a non‐competitive manner in part by chelating metal cations required for optimum catalytic rates since l ‐histidine inhibition can be overcome by addition of Zn 2+ to culture media [165]. Later work showed l ‐histidine administered intraperitoneally to rats limits thioacetamide‐induced liver fibrosis [166].…”

Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy

“…The present paper reports that the initiation of hepatic regeneration using a two‐thirds PHx model led to significantly increased levels of circulating LPA and altered hepatic expression of LPAR1, LPAR3 and LPAR6. A role for LPA–LPAR signalling has been indicated in a range of hepatic disease states . However, previously characterized LPAR subtypes (LPAR1–5) are expressed weakly, if at all, in the liver.…”

“…Signalling via LPA is involved in a diverse range of physiological and pathological events, including neoangiogenesis, neuronal growth, cardiovascular disease, fibrosis and cancer . In liver biology and pathology, LPA is involved in mediating hepatic myofibroblast migration, chemically induced liver injury, and protecting against sepsis‐induced liver damage . However, the roles of specific LPARs in regulating events within the liver have been more difficult to define because LPARs are generally not well characterized in human and rodent liver …”