Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Abstract

Many patients may administered medications like captopril (ACE inhibitor) for treatment of chronic diseases and may also take Paracetamol as an Over The Counter (OTC) drug which may interact with captopril. Therefore, the aim of this study is to evaluate of the hepatoprotective effect of captopril on liver toxicity induced by low and high dose of paracetamol in rats. This study was conducted in two phases: first study for low dose of paracetamol (300 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were treated orally either 0.9 % Normal Saline (NS), captopril 20 mg/kg, paracetamol 300 mg/kg or captopril 20 mg/kg plus paracetamol 300 mg/kg for 10 consecutive days. Second study for single high dose of paracetamol (3000 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were pretreated orally either 0.9 % Normal Saline (NS) or captopril 20 mg/kg for 7 consecutive days followed by single oral administration of Paracetamol 3000 mg/kg or normal saline. The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies. Low dose (300 mg/kg) for 10 days and high single dose (3000 mg/kg) of paracetamol produced hepatotoxic effects. While captopril 20 mg/kg showed marked protection against changes induced by low and high dose of paracetamol on the liver.

Histopathological Effects of Curcumin Versus Combined Captopril and Losartan Therapy in The Liver of Type I Diabetic Albino Rats

“…Additionally, captopril was shown by Ackerman et al (2008) to reduce the activity of glutathione reductase and peroxidase. These studies using the paracetamol-induced toxicity paradigm demonstrate that captopril has hepatoprotective properties (Al-Shaikh et al, 2016;Ali, 2012;Mahmood et al, 2014). According to Mohamed et al (2016), the main cause of liver damage is hyperglycemia-induced oxidative stress, hence a combination of losartan and captopril may be more effective in reducing it.…”

The possible effect of coenzyme Q10 and captopril on acetaminophen-induced encephalopathy in rats: possible influence on autophagy, antioxidant and Na+/K+ ATPase

“…Fouad and Jresat [49] reported that CoQ10 attenuated APAP-induced hepatotoxicity via inhibiting lipid peroxidation and inducible nitric oxide (NO) synthase, thus decreasing NO production and preventing NO-induced depletion of glutathione and catalase. Al-Shaikh et al [50] reported that captopril given to rats (20 mg/kg/day orally for 10 days) has hepatoprotective effects against APAP overdose, which might be attributed to its sulfhydryl group that is not present in other ACE inhibitors that acts as a free radical scavenger. In addition, captopril is reported to ameliorate oxidative stress by enhancing total glutathione content as well as glutathione peroxidase and glutathione reductase activities in various mouse tissues [51].…”