Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat J.I. Sotelo-Fe ´lix a, *, D. Martinez-Fong b , P. Muriel c , R.L. Santilla ´n d , D. Castillo d , P. Yahuaca e a Departamento de Biomedicina Molecular, CINVESTAV-I.P.N., Apartado Postal 14-740, Mexico, D.F. 07000, Mexico b Departamento de Fisiologı ´a, Biofı ´sica y Neurociencias, CINVESTAV-I.P.N., Mexico, D.F. 07000, Mexico c Departamento de Farmacologı ´a y Toxicologı ´a, CINVESTAV-I.P.N., Mexico, D.F. 07000, Mexico d Departamento de Quı ´mica del Centro de Investigacio ´n y de Estudios Avanzados del I.P.N., Mexico, D.F. 07000, Mexico e Departamento de Farmacologı ´a de la Facultad de Medicina de la Universidad Auto ´noma de Zacatecas, Zacatecas, Mexico Received 31 July 2000; received in revised form 30 April 2001; accepted 29 May 2001 Abstract The effect of oral administration of Rosmarinus officinalis L. (Lamiaceae) on CCl 4 -induced acute liver injury was investigated. Rats were daily treated with the plant extract at a dose of 200 mg/kg corresponding to 6.04 mg/kg of carnosol as determined by reverse phase high-performance liquid chromatography. The treatment was initiated 1 h after CCl 4 administration and Rosmarinus officinalis fully prevented CCl 4 effect on hepatic lipid peroxidation after 24 h of CCl 4 administration. The increase in bilirubin level and alanine aminotransferase activity in plasma induced by CCl 4 was completely normalized by Rosmarinus officinalis . The treatment also produced a significant recovery of CCl 4 -induced decrease in liver glycogen content. CCl 4 did not modify the activity of liver cytosolic glutathione S -transferase (GST) compared with that of control groups. However, Rosmarinus officinalis increased liver cytosolic GST activity and produced an additional increment in plasma GST activity in rats treated with CCl 4 . Histological evaluation showed that Rosmarinus officinalis partially prevented CCl 4 -induced inflammation, necrosis and vacuolation. Rosmarinus officinalis might exert a dual effect on CCl 4 -induced acute liver injury, acting as an antioxidant and improving GST- dependent detoxification systems. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Antioxidant; Scavenger; Free radicals; Hepatoprotector 1. Introduction Extracts of Rosmarinus officinalis L. (Lamiaceae) have been widely used as a preservative in food industry due to the antioxidant activity of some of its constitu- ents such as carnosol and carnosic acid (Chang et al., 1977; Inatani et al., 1983; Joyeux et al., 1990; Aruoma et al., 1992; Haraguchi et al., 1995; Frankel et al., 1996). In vitro oxidative stress models have been used as a tool to show that both carnosol and carnosic acid are good scavengers of peroxyl radicals and are able to block the formation of the hydroxyl radical generated in non-lipid systems (Aruoma et al., 1992). In addition, these compounds have been shown to inhibit in a dose- dependent manner the non-enzymatic-induced lipid peroxidation in liver microsomes when incubated in the presence of FeCl 3 (Aruoma et al., 1992) or Fe(NO 3 ) 3 (Haraguchi et al., 1995). In isolated rat hepatocytes, an aqueous extract of Rosmarinus officinalis has been shown to significantly reduce tert-butylhydroperoxide effects on lipid peroxidation and the release of lactico- dehydrogenase and aspartate aminotransferase (Joyeux et al., 1990). Oxidative stress is one of the mechanisms involved in acute hepatotoxicity by CCl 4 (Muriel and Mourelle, 1990). This hepatotoxin is rapidly transformed to free radical trichloromethyl (CCl 3 + ) by cytochrome P450- * Corresponding author. Tel.:  /52-5-747-3800x5168; fax:  /52-5- 747-7105. E-mail address: soteloj@cantera.reduaz.mx (J.I. Sotelo-Fe ´lix). Journal of Ethnopharmacology 81 (2002) 145  /154 www.elsevier.com/locate/jethpharm 0378-8741/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0378-8741(02)00090-9