Abstract
Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. However, Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal gland, has been shown to possess a multi-targeted antioxidant activity which is also effective against lipid peroxidation induced in various animal models and against various human disorders. In this study, the preventive effect of DHEA against PCM-induced nephrotoxicity was examined. Rats were divided into four groups containing 10 rats each, as follows: A control: Received normal saline, Vehicle treated: Received the vehicle (5% DMSO), PCM model (750 mg kg-1), PCM and DHEA treated: Received concomitant dose of PCM (750 mg kg-1) + DHEA (250 mg kg-1), respectively, for 4 consecutive weeks. All treatment were given orally to animals. Our results show that co-treatment of DHEA with PCM prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (p<0.05) level of serum creatinine, urea and BUN with parallel significant increases in serum protein, Cr clearance and kidneys weights. Furthermore, DHEA was able to induce a significant increment (p<0.05) of renal levels of reduced Glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Glutathione Peroxidise (GPx). An effect that was accompanied with a significant decrease in renal lipid peroxides levels (MDA). The nephroprotective effects of DHEA was confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. In conclusion, DHEA at a daily dose of 250 mg kg-1 has a protective role against PCM-induced nephrotoxicity in rats and the process is probably mediated through its antioxidant properties.
Highlights
Paracetamol (PCM ) or Acetaminophen is an effective, well tolerated, widely used over-the-counter analgesic antipyretic agent (Jalan et al, 2006) with more than 1 billion tablets sold annually in the United States alone (Nourjah and Wiley, 2002)
Our results show that co-treatment of DHEA with PCM prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (p
The group of rats received PCM concurrent with administration of 250 mg kg−1 of DHEA showed higher food and water consumption and weighed significantly higher and the weights of their kidneys were significantly higher (p
Summary
Paracetamol (PCM ) or Acetaminophen (marketed as Panadol in Great Britain, Tyelonol in the US) is an effective, well tolerated, widely used over-the-counter analgesic antipyretic agent (Jalan et al, 2006) with more than 1 billion tablets sold annually in the United States alone (Nourjah and Wiley, 2002). It was reported that PCM is safe when administered at recommended doses (Ozkaya et al, 2010). It is estimated that over 56,000 emergency visits and nearly 500 deaths occur in the US annually, resulting from PCM toxicity, owing to either intentional or accidental overdoses (Nourjah and Wiley, 2002). These figures continue to rise (Bernal, 2003). The safety of PCM even at therapeutic doses has generated considerable debate (Jalan et al, 2006)
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