Protection against paracetamol-induced hepatic injury by prazosin pre-treatment in CD-1 mice

Clement, Y; Williams, Arlene

doi:10.1016/j.mrfmmm.2005.03.028

Cited by 10 publications

(4 citation statements)

References 18 publications

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“…There was no difference in the recovery of hepatic paracetamol-SG conjugate 1 h after receiving paracetamol ± prazosin (% dose recovered ± s.e.mean; paracetamol 11.03±1.83, paracetamol þ prazosin 14.58± 2.00). Data previously generated within this laboratory has also confirmed that prazosin has no effect on paracetamolglucuronide formation and therefore is unlikely to alter elimination via phase II metabolism (Clement and Williams, 2005).…”

Section: Prazosin Does Not Suppress Paracetamol-induced Gsh Depletionsupporting

confidence: 64%

α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

Randle

Sathish

Kitteringham

et al. 2008

British J Pharmacology

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Background and purpose: Paracetamol, a major cause of acute liver failure (ALF) represents a significant clinical problem. Adrenoceptor stimulation or antagonism can modulate chemical-induced hepatotoxicity. We investigated the role of endogenous catecholamines and a 1 -adrenoceptors in the development of paracetamol-induced hepatotoxicity. Experimental approach: Paracetamol (3.5 mmol kg À1 ) was administered to male CD-1 mice, with and without a 1 -adrenoceptor antagonists (prazosin, doxazosin, terazosin and tamsulosin; 35.7 mmol kg À1 ). Serum transaminases and hepatic glutathione (GSH) levels were assessed as markers of hepatic damage. Paracetamol bioactivation was assessed by covalent binding, hepatic and urinary conjugate formation and uridine glucuronosyltransferase activity. Plasma catecholamines levels and hepatic congestion were also analysed. Key results: Plasma catecholamine levels were significantly elevated 5 h post paracetamol administration. Prazosin prevented hepatotoxicity when administered 1 h before a toxic paracetamol insult and importantly, when administered up to 1 h post paracetamol injection. Prazosin had no effect on paracetamol-induced depletion of hepatic GSH, paracetamol bioactivation or paracetamol-induced transcription of defence genes. Paracetamol toxicity is associated with marked accumulation of erythrocytes within hepatic sinusoids and prazosin completely prevented this accumulation. Conclusion and implications: Paracetamol-induced hepatocellular damage is associated with increased circulating catecholamines. a 1 -Adrenoceptor antagonists conferred complete protection from paracetamol -induced hepatotoxicity. Protection was associated with absence of hepatic erythrocyte accumulation. Increased catecholamine levels may contribute to the pathophysiology of paracetamol-induced hepatotoxicity by compromising hepatic perfusion. Protection against paracetamol toxicity by a 1 antagonists in mice has implications for therapeutic management of patients presenting with paracetamol overdose and ALF.

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Section: Prazosin Does Not Suppress Paracetamol-induced Gsh Depletionsupporting

confidence: 64%

α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

Randle

Sathish

Kitteringham

et al. 2008

British J Pharmacology

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“…At all time points, the formulation was found free of fibrous encapsulation, which would be indicative of a foreign body response. ALT levels in both control mice and those injected with the formulation (25 ± 8 and 17 ± 4 U/l, respectively) remained well below 200 U/l, levels which are indicative of hepatotoxicity in mice (Clement and Williams, 2005;Masubuchi et al, 2005;Wang et al, 2007). As it is plausible that introduction of foreign material into the body can result in immune response and tissue injury, resulting in the activation of an inflammatory reaction (Anderson, 2001;Pavithra and Doble, 2008), we monitored circulating levels of IL-6, a systemic pro-inflammatory mediator.…”

Section: In Vivo Dtx Distributionmentioning

confidence: 87%

Chitosan–phospholipid blend for sustained and localized delivery of docetaxel to the peritoneal cavity

Zahedi

Souza

Piquette-Miller

et al. 2009

International Journal of Pharmaceutics

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“…The hepatoprotective effects of Prazosin were reported previously 16 17 . It is reported that hepatotoxicity and oxidative stress induced by paracetamol 29 and Acetaminophen 30 could be relieved by Prazosin in mice. Liver function, serum MDA and GSH levels were backed to the normal condition in paracetamol-induced hepatotoxicity in rabbits 31 .…”

Section: Discussionmentioning

confidence: 99%

Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats

et al. 2023

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Acute kidney injury (AKI) is a common subsequent problem after many medical conditions. AKI is associated with distant organ dysfunction where systemic inflammation and oxidative stress play major roles. In this study, the effect of Prazosin, an α1-Adrenergic receptor antagonist, was investigated on the liver injury induced by kidney ischemia-reperfusion (I/R) in rats. Male adult Wistar rats (n=21) were divided into three groups: sham, kidney I/R, and kidney I/R pre-treated with Prazosin (1 mg/kg). Kidney I/R was induced by vascular clamping of the left kidney for 45 min to reduce the blood flow. Oxidative and antioxidant factors along with apoptotic (Bax, Bcl-2, caspase3), and inflammatory (NF-κβ, IL-1β, and IL-6) factors were measured in the liver at protein levels. Prazosin could reserve liver function (p<0.01) and increase glutathione level (p<0.05) after kidney I/R significantly. Malonil dialdehyde (MDA), a lipid peroxidation marker, was diminished more significantly in Prazosin-treated rats compared to the kidney I/R group (p<0.001). Inflammatory and apoptotic factors were diminished by Prazosin pre-treatment in the liver tissue (p<0.05). Pre-administration of Prazosin could preserve liver function and decrease its inflammatory and apoptotic factors under kidney I/R conditions.

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Protection against paracetamol-induced hepatic injury by prazosin pre-treatment in CD-1 mice

Cited by 10 publications

References 18 publications

α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

Chitosan–phospholipid blend for sustained and localized delivery of docetaxel to the peritoneal cavity

Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats

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Protection against paracetamol-induced hepatic injury by prazosin pre-treatment in CD-1 mice

Cited by 10 publications

References 18 publications

α1‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

α1‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

Chitosan–phospholipid blend for sustained and localized delivery of docetaxel to the peritoneal cavity

Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats

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α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice

α₁‐Adrenoceptor antagonists prevent paracetamol‐induced hepatotoxicity in mice