Abstract

Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has several pharmacological properties such as antioxidant, anti-inflammation and anti-apoptotic effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in rats. Forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10mg/kg, acetaminophen, acetaminophen + carvacrol 5mg/kg, and acetaminophen + carvacrol 10mg/kg. Animals received a single dose of acetaminophen (500mg/kg), then were treated with carvacrol for 1 week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure, renal perfusion pressure, renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The Western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10mg/kg) significantly increased the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10mg/kg group versus acetaminophen group (P < 0.05). Also, carvacrol significantly decreased the cleaved caspase-3, Bax proteins expression level, and kidney tissue damage score in the acetaminophen + carvacrol 10mg/kg group versus acetaminophen group (P < 0.05). This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress and apoptosis biochemical factors.

Highlights

  • Acetaminophen is widely applied as a febrifuge and analgesic drug worldwide, but it induces kidney injury at high doses administration [1]

  • This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress, apoptosis and its antioxidant effects

  • Our result showed that serum creatinine and blood urea nitrogen (BUN) increased in acetaminophen (500 mg/kg) administered animals when compared to control (P < 0.001 and P < 0.01 respectively, Table 1)

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Summary

Introduction

Acetaminophen (paracetamol) is widely applied as a febrifuge and analgesic drug worldwide, but it induces kidney injury at high doses administration [1]. The mechanisms involved in renal injury following high-dose acetaminophen administration are not well understood, it has been shown that N-acetylcysteine is used to treat acetaminophen-induced hepatotoxicity. It has been shown that by increasing free radicals in the body, an imbalance is created between oxidants and antioxidants, which is defined as oxidative stress, leading to oxidative damage [12] In this regard, it has been observed that carvacrol can effectively neutralize free radicals such as peroxyl radicals, superoxide radicals, and hydrogen peroxide [13]. Since acetaminophen overdose administration can induce acute renal damage, this study was designed to evaluate the protective effect of carvacrol on acetaminophen-induced renal damage in male rats

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