Abstract
Paracetamol (PCM) is a well-known drug widely used for its analgesic and antipyretic properties. PCM is generally considered as safe but overdose of PCM can cause nephrotoxicity. Traditionally, herbs have been used for the treatment of drug or toxin-induced renal disorders and numerous medicinal plants were tested for nephroprotection effect in PCM-induced nephrotoxicity model. The aim of the present study was to evaluate the protective effect of the herbal extract Eurycoma longifolia (EL) against PCM-induced nephrotoxicity rat model. Forty Wistar rats were randomly divided into five groups of eight rats each: control (vehicle 10 ml/kg), PCM alone (200 mg/kg PCM), EL 100 (EL 100 mg/kg+200 mg/kg PCM), EL 200 (EL 200 mg/kg+200 mg/kg PCM), and EL 400 (EL 400 mg/kg+200 mg/kg PCM). All animals from control group received vehicle daily and animals from groups PCM alone, EL 100, EL 200, and EL 400 received repeated dose of PCM and the assigned treatment of EL daily for a period of 14 days. On the 15th day, serum creatinine, blood urea nitrogen, protein, and albumin were measured in blood and creatinine clearance was measured in urine collected over 24 hours. Kidney sections of all experimental groups underwent histopathological analysis. There was a significant (p<0.05) increase in serum creatinine and blood urea levels in the PCM alone group compared to the treatment groups due to nephrotoxicity. In the treatment groups, there was a dose-dependent protection against PCM-induced changes observed in serum total protein, albumin, urea, and creatinine. Significant (p<0.05) drop was seen in serum creatinine and blood urea content in EL 200 and EL 400 groups. Creatinine clearance significantly increased for EL 200 (p<0.01) and EL 400 (p < 0.001) groups. Serum total protein and serum albumin content were significantly increased (p<0.05) in EL 200 and EL 400 groups compared to PCM alone group. Histopathological examination (H&E staining) of the rat kidneys revealed severe degeneration in the PCM alone group, while there was evidence of significant dose-dependent protection in the treatment groups against PCM-induced changes. The serum and urine biochemical results and histopathology analysis of the kidney indicate the nephroprotective potential of EL extract against PCM-induced nephrotoxicity.
Highlights
Nephrotoxicity occurs when kidney-specific detoxification and excretion do not function optimally due to the damage or destruction of kidney function by exogenous or endogenous toxicants [1]
It is a water extract of the roots of Eurycoma longifolia (EL) standardised based on specification of 0.8%-1.5% eurycomanone, not less than 22% of total protein, not less than 30.0% of total polysaccharide, and not less than 40.0% of Glycosaponin
There was significant decrease in the level of creatinine clearance in the PCM alone group compared to control group. This decrease was prevented in treatment groups, with a significant increase in the creatinine clearance levels in the EL 200 (p
Summary
Nephrotoxicity occurs when kidney-specific detoxification and excretion do not function optimally due to the damage or destruction of kidney function by exogenous or endogenous toxicants [1]. Drug-induced nephrotoxicity remains a major problem as use of nephrotoxic drugs is unavoidable in clinical setting. Overdose of PCM in human is relatively common due to self-administration and is often associated with hepatic [3,4,5] and renal damage [6,7,8,9]. Even if nephrotoxicity is less common than hepatotoxicity in PCM overdose, renal tubular damage and acute renal failure can occur even in the absence of liver injury [10,11,12] and can be fatal in humans and experimental animals [13,14,15].To date, numbers of studies have been published to prove nephroprotective effect of medicinal plants by using PCM-induced nephrotoxicity in rats.
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