EVALUATION OF Trevo®, A PHYTOPHARMACEUTICAL PRODUCT FOR PROTECTIVE EFFECTS ON ACETAMINOPHEN-INDUCED OXIDATIVE STRESS AND HEPATOTOXICITY

Abstract

Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug which at high doses leads to undesirable side effects such as hepatotoxicity. Trévo™ is a popular phytopharmaceutical product reputed to enhance overall wellbeing among other health benefits. This study was designed to investigate the antioxidant and hepatoprotective properties of Trévo™ against acetaminophen intoxication in rats. Animals were randomly divided into seven groups (I-VII) of six animals per group. Group I (normal control) received neither the Trévo™ nor acetaminophen for 14 days while animals in group II (hepatotoxic induced group) received distilled water for 14 days and were administered acetaminophen (2 g/kg b.wt) orally on day 14. Animals in groups III-V were pretreated with varying doses of Trévo™ (1.5 ml/kg b.wt, 3.0 ml/kg b.wt and 4.5 ml/kg b.wt) for 14 days orally followed by a single dose of acetamionophen (2 g/kg b.wt) on day 14. Group VI and VII were pretreated with azathioprine( 2 mg/kg b.wt) and silymarin (25 mg/kg b.wt) for 14 days respectively followed by a single dose of acetaminophen (2 g/kg b.wt) on day 14. The animals were sacrificed and biochemical parameters were estimated after 24 hrs following the administration of acetaminophen. The degree of protection were assessed through the evaluation of the activities of alanine aminotransferase (ALT), aspartate (AST) alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), levels of malondialdehyde (MDA) as well as the levels of bilirubin (BIL) and albumin (ALB) in the serum. In addition, superoxide dismutase (SOD), catalase (CAT), total protein level (TP) and reduced glutathione (GSH) were quantified in liver homogenates. Histopathological examination of liver sections were also carried out. Acetaminophen-induced hepatotoxicity was confirmed by an increase (P<0.05) in serum AST, ALT, ALP, GGT and LDH activities in the induced group compared with the control. In the liver, the trend was opposite of what was obtained in the serum as the level of AST, ALT and ALP in the liver of acetaminophen treated group significantly decreases as compared to the control, while the liver level of Trévo™ pretreated group were also significantly increased (p<0.01) as compared to the acetaminophen treated group. Albumin level was also decreased in acetaminophen treated group accompanied by a significant increase (P<0.05) in albumin level of Trévo™ pretreated group. Acetaminophen-induced oxidative stress was manifested by an increase (P<0.05) in MDA level, depletion of reduced glutathione (GSH) and decreases in SOD and CAT activities in the induced group compared with the control. Administration of Trévo™ ameliorated altered activities and levels of hepatoprotective and antioxidant indices and was more effective comparable with silymarin and azathioprine. Histopathological findings supported the biochemical observations. The present study demonstrated that Trévo™ protected against acetaminophen-induced oxidative stress and hepatotoxity and suggested that its antioxidant activity and salubrious effect on the liver may contribute to the general wellbeing experience by users.