Drug and Chemical Toxicology, 2010; 33(1): 77–87
R E S E A R C H A R T I C L E
Acetaminophen perturbed redox homeostasis in Wistar rat liver: protective role of aqueous Pterocarpus osun leaf extract
Taofeek O. Ajiboye1, Amadu K. Salau2, Musa T. Yakubu1, Adenike T. Oladiji1, Musbau A. Akanji1, and Joseph I. Okogun3 1Phytomedicine and Toxicology Research Laboratory, Department of Biochemistry, University of Ilorin, Ilorin, Nigeria, 2Biochemistry and Nutrition Unit, Department of Chemical Sciences, Fountain University, Osogbo, Nigeria, and 3Medicinal Plant Research and Traditional Medicine Department, National Institute for Pharmaceutical Research and
Development, Abuja, Nigeria
Address for Correspondence: Taofeek O. Ajiboye, Phytomedicine and Toxicology Research Laboratory, Department of Biochemistry, University of Ilorin,
PMB, 1515, Postal code: 24003, Tunde Idiagbon Road, Ilorin, Nigeria; Fax: +234 31 221593; E-mail: firstname.lastname@example.org (Received 08 May 2009; revised 17 June 2009; accepted 08 July 2009)
Reactive oxygen species (ROS), as well as reactive nitrogen species (RNS), transiently or permanently, indirectly or directly, cause oxidative damage to cellular macromolecules, such as nucleic acids, lipids, and proteins (Thompson, 2004). This oxidative damage has been implicated in numerous disease conditions, including cancer, diabetes, malaria, cardiovascular disease, and many others (Thompson, 2004).
Acetaminophen (Figure 1), an antipyretic/analgesic drug, has been shown to generate free radicals, which, subsequently, results in oxidative damage to cellular macromolecules. Acetaminophen produces centrilobular hepatic necrosis (Mitchell et al., 1973a). It has been hypothesized that the initial step in acetaminophen toxicity is metabolism to N-acetylp-benzoquinone imine (NAPQI) by cytochrome P 450 2E1, leading to the depletion of glutathione (GSH) and covalent adduct formation (Jaeschke et al., 2002). Nitric oxide (NO) synthesis and superoxide generation also occurs, which, subsequently, leads to the formation of peroxynitrites. However, GSH detoxifies peroxynitrites (Sies et al., 1997), but the depletion of GSH by NAPQI (Mitchell et al., 1973b) creates a loophole for peroxynitrites to attack cellular
ISSN 0148-0545 print/ISSN 1525-6014 online © 2010 Informa UK Ltd
This study investigates the in vitro antioxidant potentials and attenuation of acetaminophen-induced redox imbalance by Pterocarpus osun Craib (Fabaceae) leaf in Wistar rat liver. The in vitro antioxidant activity of the extract (0.2-1.0 mg/mL) was evaluated using 2,2-diphenyl-1-picrylhydrazl (DPPH), hydrogen peroxide, superoxide ion, 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS), and ferric ion. The extract (150 and 300 mg/kg body weight) significantly (P<0.05) attenuated the altered liver and serum enzymes of acetaminophen treated animals. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities as well as vitamins C and E, and glutathione levels were significantly (P<0.05) elevated by the extract. The activities of uridyl diphosphoglucuronosyl transferase (59%), quinone oxidoreductase (53%), and glutathione S-transferase (73%) significantly increased.
The extract of P. osun leaf extract at 1. 0 mg/mL scavenged the DPPH, hydrogen peroxide, superoxide ion, and ABTS at 94, 98, 92, and 86%, respectively, while ferric ion was significantly reduced. There was attenuation of malondialdehyde and lipid hydroperoxide. The results indicates that P. osun leaves attenuated acetaminophen-induced redox imbalance, possibly acting as free radical scavenger, inducer of antioxidant and drug-detoxifying enzymes, which prevented/reduced lipid peroxidation.
Keywords: Pterocarpus osun; acetaminophen; antioxidant; free radical; redox imbalance; drug-detoxifying enzyme; lipid peroxidation http://www.informahealthcare.com/dct
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Fo r p er so na l u se o nl y. 78 Taofeek O. Ajiboye et al. macromolecules by nitrating tyrosine (Beckman, 1996; Pryor and Squadrito, 1995). Aside the toxicity that results from peroxynitrites, superoxide ion can also cause lipid peroxidation (LPO) (Jaeschke et al., 2002). The mitochondria are the power house of the cell, and a proton gradient across their inner membrane drives the turbines that produce adenosine triphosphate (ATP), the fuel used by the machinery of the cell. There is evidence that if the proton gradient gets too high, superoxide is generated, which dismutates into hydrogen peroxide, and eventually to nontoxic molecules (H 2
O and O 2 ) by catalase. It may also undergo Fenton reaction, producing hydroxyl radicals which leads to oxidative damage. Thus, acetaminophen causes oxidative damage by generating peroxynitrites, superoxide, and H 2
O 2 , which, subsequently, results in LPO, protein adduct formation, and depletion of the antioxidant system.
Macronutrients, such as fibers, carotenoids, allium compounds, dithiolthiones/glucosinolates, isothiocyanates, terpenoids, phytoestrogens, protease inhibitors, phytic acids, flavonoids, phenolics, plant sterols, and saponins have been shown to prevent oxidative damage arising from ROS and RNS by scavenging free radicals, inducing the antioxidant systems (both enzymic and nonenzymic) and drug-detoxification mechanisms (Krishnaswamy and Polasa, 2001).
These micronutrients are widely available in medicinal plants, contributing to some of their medicinal properties.
Pterocarpus osun Craib (Fabaceae) commonly known as padouk (English) and osun (YorubaWestern Nigeria) is endemic to southern Cameroon,
Congo, Gabon, Equitorial-Guinea, Nigeria, and Zaire (Burkill, 1995). It has distinct pickles on twigs and young branches. The trees are about 30 m tall, with a girth size of about 2.4 m. The fruits are dark brown and velvety when young, with short shift and often pickles, mostly surrounding the center (Keay et al., 1964).