Journal of Experimental and Integrative Medicine 2011; 1(3):165-166 www.jeim.org 165 Current issues with paracetamol induced toxicity Halil Yaman 1 , Salim Isbilir 2 , Erdinc Cakir 1 , Bulent Uysal 3 1 Department of Medical Biochemistry, Gulhane Military Medical Academy, Ankara, Turkey. 2 Department of Biochemistry, Beytepe Military Hospital, Ankara, Turkey. 3 Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey. Paracetamol (acetaminophen; APAP), a commonly-used analgesic and anti-pyretic drug, is usually safe when administered at therapeutic doses in children. However, at overdoses, APAP has the potential for causing fulminant hepatic necrosis and nephrotoxicity in both humans and animals [1]. In pre-school children, many poisonings are due to chemical or pharmaceutical preparations like APAP which is an important example for poisoning with pharmaceutics [2]. Liver has an important role in the metabolism of toxic chemicals, certain drugs and environmental pollutants [3]. Using the cytochrome P450 pathway, APAP is converted to a highly toxic metabolite, namely N–acetyl–p–benzoquinamine (NAPQI) [4]. By this way, overdose of APAP leads to accumulation of NAPQI, mitochondrial dysfunction and leads to acute hepatic necrosis [4]. In the present issue of the Journal of Experimental and Integrative Medicine, we read with great interest the published article by Anbarasu et al [5] reporting a protective effect of a plant extract, Pisonia aculeata, in an experimental model of APAP-induced hepatotoxicity. The extracts of P.aculeata contain alkaloids, phenolic compounds, tannins, saponnins and flavonoids. In India, its leaves and barks have been used to treat several medical conditions such as liver disorders, inflammation, swelling, cough and tumors [6]. In the abovementioned particular work, Anbarasu et al have shown that the protective effects of P.aculeata in the rat APAP-hepatotoxicity model may be related to inhibition of lipid peroxidation and enhancement of antioxidant enzyme levels indicating a free radical scavenging action. Furthermore, they underlined that the antioxidant and hepatoprotective activities of P.aculeata may be due to its flavonoid contents [5]. In the medical literature, APAP-induced hepato- and nephrotoxicity is to see as a widely used experimental animal model [3, 7, 8-13]. Liver injury by APAP overdoses dues to increased production of reactive oxygen species, antioxidant depletion, decreased antioxidant enzymes levels, and cytokine upregulation [7]. Although nephrotoxicity is less common than hepatotoxicity in APAP overdose, the occurrence of renal tubular damage and acute renal failure is greater in more severely poisoned patients and is often observed in those who developed major liver injury [14]. Measurements of alanine aminotransferase and aspartate aminotransferase have long been used in order to detect liver damage [7]. Recently, it was shown that in APAP-induced hepato- and nephrotoxicity, serum neopterin levels could alternatively be a sensible marker for risk evaluation in cases with overdose APAP consuming history [7, 13]. The (im)balance between oxidants and antioxidant defense mechanisms seem to play an important role in the APAP-induced toxicity. In clinics, the well known antioxidant N- acetylcysteine is widely used as an antidote for APAP intoxication [15]. On the other hand, in order to provide more promising outcome, alternative and adjunctive treatment approaches are being tested. In a study performed by Demirbag et al, medical ozone therapy improved antioxidant mechanism and limited oxidative stress in rats with APAP- induced nephrotoxicity [16]. Moreover, herbal treatments of many diseases including hepatopathy are increasing in many countries [17]. Mittal et al have declared that Polygonum bistorta has hepatoprotective effects in APAP-induced hepatotoxicity [3]. In another study, Zhao et al have shown that rhein ameliorated oxidative injuries in the liver and kidney, as assessed by both biochemical and histopathological analysis [8]. In a recently published article, Wang et al evaluated extracts of the plant Gentiana manshurica Kitagawa in a model of APAP hepatotoxicity [11]. The extracts of herbals may show their protective effects by increasing antioxidant enzyme levels, increasing the amount of antioxidants such as glutathione, and consequently reducing lipid peroxidation. Editorial