Hepatitis aguda por candesartan

Vallejo, I; García-Morillo, Salvador; Pamies, E.

doi:10.1016/s0025-7753(00)71672-1

Cited by 15 publications

(2 citation statements)

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“…Therefore, it is likely that AT-II harbors specific roles in (diseased) hepatocytes and AT-II antagonist therapy may lead to hepatotoxicity. Indeed, ACEi- and ARB-induced hepatocellular injury and liver damage has been reported previously [15]–[20]. Several mechanisms have been suggested for ARB-induced hepatotoxicity and cholestasis such as metabolic idiosyncrasy and immune mechanisms.…”

Section: Discussionmentioning

confidence: 97%

“…On the other hand, there are multiple (case) reports indicating that ARBs and ACEis may induce hepatocellular injury and/or cholestasis [15]–[24]. Losartan and candesartan were found to induce hepatocellular injury in hypertensive patients with normal liver function tests prior to the start of the therapy [15]–[20]. Irbesartan therapy leads to hepatocyte cholestasis and degeneration in hypertensive patients [21], [22] and valsartan has been reported to induce lobular necrosis and inflammation in the liver [23], [24].…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

et al. 2012

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Angiotensin II (AT-II) is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R) and thereby activates hepatic stellate cells (HSCs). AT-II receptor blockers (ARBs) are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-1R blockers may induce hepatocyte injury. Therefore, we investigated the effect of AT-II and its receptor blockers on cytokine-, oxidative stress- and bile salt-induced cell death in hepatocytes. Primary rat hepatocytes were exposed to TNF-α/Actinomycin D, the ROS-generating agent menadione or the bile salts: glycochenodeoxycholic acid (GCDCA) and tauro-lithocholic acid-3 sulfate (TLCS), to induce apoptosis. AT-II (100 nmol/L) was added 10 minutes prior to the cell death-inducing agent. AT-1R antagonists (Sartans) and the AT-2R antagonist PD123319 were used at 1 µmol/L. Apoptosis (caspase-3 activity, acridine orange staining) and necrosis (Sytox green staining) were quantified. Expression of CHOP (marker for ER stress) and AT-II receptor mRNAs were quantified by Q-PCR. AT-II dose-dependently reduced GCDCA-induced apoptosis of hepatocytes (−50%, p<0.05) without inducing necrosis. In addition, AT-II reduced TLCS-induced apoptosis of hepatocytes (−50%, p<0.05). However, AT-II did not suppress TNF/Act-D and menadione-induced apoptosis. Only the AT-1R antagonists abolished the protective effect of AT-II against GCDCA-induced apoptosis. AT-II increased phosphorylation of ERK and a significant reversal of the protective effect of AT-II was observed when signaling kinases, including ERK, were inhibited. Moreover, AT-II prevented the GCDCA-induced expression of CHOP (the marker of the ER-mediated apoptosis).ConclusionAngiotensin II protects hepatocytes from bile salt-induced apoptosis through a combined activation of PI3-kinase, MAPKs, PKC pathways and inhibition of bile salt-induced ER stress. Our results suggest a mechanism for the observed hepatocyte-toxicity of Sartans (angiotensin receptor blockers, ARBs) in some patients with chronic liver injury.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

et al. 2012

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Current Awareness

2001

Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Hepatotoxicity of Cardiovascular and Antidiabetic Drugs

Marzio

Navarro

2013

Drug-Induced Liver Disease

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Hepatitis aguda por candesartan

Cited by 15 publications

References 4 publications

Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

Current Awareness

Hepatotoxicity of Cardiovascular and Antidiabetic Drugs

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