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

Abstract

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.

Effects of prazosin treatment on liver enzymes are moderated by alcohol withdrawal symptoms in individuals with alcohol use disorder

“…Elevation of pro-inflammatory markers in AW also occur independent of level of alcohol consumption, and are thought of as allostatic load (Girard et al, 2019). Prazosin was recently found to decrease inflammatory and apoptotic factors in liver tissue injury induced by kidney ischemia-reperfusion (Khajepour et al, 2023).…”

“…Prazosin is a nonselective antagonist of alpha-1 adrenergic receptors that are known to be involved in regulation of hepatocyte proliferation and liver regeneration after hepatic injury (Cruise et al, 1987;Michalopoulos & DeFrances, 1997). Interestingly, prazosin has been found to preserve liver function and decrease inflammatory and apoptotic factors in hepatocytes (Khajepour et al, 2023), but studies have also shown that by blocking alpha-1 adrenergic receptors, prazosin decreases DNA synthesis and rejuvenation of damaged liver cells (Cruise et al, 1987;Han et al, 2008). Elevated liver enzymes and inflammatory markers are both released into the bloodstream by alcohol-damaged liver cells (Kerner et al, 2005) and are associated with greater AW and higher risk of developing DT (Borah et al, 2017;Goodson et al, 2014;Vatsalya et al, 2023;Wetterling et al, 1994;Yen et al, 2017).…”