Intracellular balance of oxidative stress and cytoprotective molecules in damaged interlobular bile ducts in autoimmune hepatitis and primary biliary cirrhosis: <i>In situ</i> detection of 8‐hydroxydeoxyguanosine and glutathione‐S‐transferase‐pi

Kadokawa, Yoshiko; Ohba, Kazuo; Omagari, Katsuhisa; Akazawa, Shiho; Hayashida, Kenji; Ohnita, Ken; Takeshima, Fuminao; Mizuta, Yohei; Kohno, Shigeru

doi:10.1111/j.1872-034x.2007.00093.x

Cited by 9 publications

(3 citation statements)

References 33 publications

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“…ROS are involved in apoptosis in the biliary epithelium, and the antioxidant system may play a role in protecting against the progression of biliary destruction [40]. In PBC, apoptosis can be prevented by the presence of a relatively preserved intracellular glutathione concentration; this factor plays a key role in preventing progressive bile duct loss following bile duct autoimmune injury [41,42]. In asymptomatic PBC, we showed that alcohol consumption, even in only low amounts (between 20 and 30 g/day), was predictive of the severity of disease.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis

et al. 2010

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“…However, plasma GSH peroxidase activity was significantly higher in AIH patients with elevated ALT values compared with normal controls [86]. In AIH patients, oxidative stress and DNA damage are involved in the bile duct injury similar to primary biliary cirrhosis [87]. Moreover, homologs of NADPH oxidases (NOXs) are major sources of ROS and are expressed in human livers with stage 2-3 AIH [88].…”

Section: The Non-genetic Role Of Vitamin D In Autoimmune Hepatitismentioning

confidence: 99%

The Role of Vitamin D in Autoimmune Hepatitis

Luong

2013

J Clin Med Res

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Autoimmune hepatitis is an inflammation of the liver characterized by the presence of peri-portal hepatitis, hypergammaglobulinemia, and the serum autoantibodies. The disease is classified into 2 distinct types according to the nature of auto-antibodies. Disturbances of the calcium-parathyroid hormone-vitamin D axis are frequently associated with chronic liver disease. Patients with AIH have a high prevalence of vitamin D deficiency. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AIH pathology, namely, the major histocompatibility complex class II molecules, vitamin D receptors, toll-like receptors, cytotoxic T lymphocyte antigen-4, cytochrome P450 CYP2D6, regulatory T cells (Tregs) and the forkhead/winged helix transcription factor 3. Vitamin D also exerts its effect on AIH through non-genomic factors, namely, mitogen-activated protein kinase signaling pathways, γδT cells, interferon-gamma nitric oxide synthase, and reactive oxygen stress. In conclusion, vitamin D may have a beneficial role in AIH and improves liver function in concanavalin A-induced mouse AIH. Calcitriol is best used for AIH because it is the active form of a vitamin D3 metabolite and its receptors are present in sinusoidal endothelial cells, Kupffer cells, stellate cells of normal livers, and the biliary cell line.

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“…Oxidative stress has been shown to be independently associated with more advanced stages of some cholangiopathies as for example PBC [141]. Furthermore, expression of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was preferentially detected in the nuclei of damaged interlobular bile ducts in this cholangiopathy [142,143]. In response to DNA damage, the gene encoding the cyclindependent kinase inhibitor WAF1 (aka p21) is induced by upregulated p53; WAF1 is a potent and reversible inhibitor of cell cycle progression at both the G1 and G2 checkpoints, and upregulated WAF1 induces irreversible G1 arrest and apoptosis.…”

Section: Intrinsic Pathwaymentioning

confidence: 95%

Caracterización de los efectos de protección hepática y renal del factor de crecimiento de hepatocitos en la colestasis intrahepática

Silva

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Cholestasis is a clinical syndrome common to a large number of hepatopathies, in which either bile production or its transit through the biliary tract is impaired due to functional or obstructive causes, respectively; the consequent intracellular retention of toxic biliary constituents generates parenchyma damage, largely via oxidative stressmediated mechanisms. Hepatocyte growth factor (HGF) and its receptor c-Met represent the first defense line against hepatotoxic factors, by inducing Nrf2 activation which, in turn, leads to an antioxidant and repair response. In this study, we evaluated the capability of HGF to counteract the damage caused by the model cholestatic agent, α-naphthyl isothiocyanate (ANIT). HGF had clear anti-cholestatic effects, as apparent from the improvement in both bile flow and liver function test. Histology examination revealed a significant reduction of injured areas. HGF also preserved hepatocellular tight-junctional structures. These anticholestatic effects were associated with the induction of basolateral efflux ABC transporters, which facilitates extrusion of toxic biliary compounds and its further alternative depuration via urine. The biliary epithelium seems to have been also preserved, as suggested by a normalization in serum GGT levels, CFTR expression, and cholangyocyte primary cilium structure. Finally, we are reporting that HGF also protects the kidneys and their function from the impairment provoked by ANIT-induced cholestasis (cholemic nephropathy). In conclusion, the results clearly show for the first time that HGF protects the liver and kidneys from a cholestatic injury.

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Intracellular balance of oxidative stress and cytoprotective molecules in damaged interlobular bile ducts in autoimmune hepatitis and primary biliary cirrhosis: In situ detection of 8‐hydroxydeoxyguanosine and glutathione‐S‐transferase‐pi

Abstract: In AIH, oxidative stress and DNA damage may be involved in the pathogenesis of bile duct injury in a manner similar to that found in PBC. However, relatively preserved intracellular glutathione may play a key role in preventing progressive bile duct loss following bile duct injury in AIH.

Cited by 9 publications

References 33 publications

Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis

Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis

The Role of Vitamin D in Autoimmune Hepatitis

Caracterización de los efectos de protección hepática y renal del factor de crecimiento de hepatocitos en la colestasis intrahepática

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