STUDYING THE PROTECTIVE EFFECT OF CONCOMITANT ADMINISTRATION OF DIMETHYL-4-4'-DIMETHOXY-5,6,5',6'-DIMETHYLENE DIOXYBIPHENYL-2,2'-DICARBOXYLATE (D.D.B) WITH N-ACETYLCYSTEINE (NAC) AGAINST PARACETAMOL-INDUCED HEPATOTOXICITY IN RATS
Mohammed A.M. Khalaf1, Ashraf M. Abdou1 and Heba M. Tawfik2
1Department of Forensic Medicine & Clinical Toxicology and
2Department of Pathology, Faculty of Medicine, El-Minia University
The current study was carried out to investigate the protective effect of dimethyl-4,4'- dimethoxy-5,6,5',6'- dimethylenedioxybiphenyl-2,2'- dicarboxylate (D.D.B.) against paracetamol-induced hepatotoxicity. The experimental part was performed on 80 adult albino rats divided into 4 groups of 20 rats each as follows: the 1st group received physiological saline as a control group, the 2nd group received a single oral dose of paracetamol (150 mg/kg), the 3rd group received a single oral dose of paracetamol (150 mg/kg) and treated with a 48-hours intravenous N-acetyl cysteine protocol (140 mg/kg, then 70 mg/kg every 4 hours total dose 980 mg/kg), and the 4th group received a single dose of paracetamol (150 mg/kg) and treated with the same N-acetyl cysteine regimen with concomitant administration of D.D.B. (30 mg/kg body weight orally 3 times per week / 4 weeks). All survived animals were anesthetized and blood samples were taken for biochemical analyses (SGOT and SGPT), then killed and livers were extracted for histopathological examination. The results of the present study have revealed that there was marked improvement of SGOT and SGPT values with the N-acetyl cysteine-treated animals accompanied by less histopathological damage when compared to the paracetamol-induced biochemical and histopathological changes. Moreover, the addition of D.D.B. to N-acetyl cysteine as a concomitant therapy had lowered the values of SGOT and SGPT significantly and produced much less histopathological changes when compared to the animal group treated with N-acetyl cysteine alone. Accordingly, it could be concluded that D.D.B. has a protective effect against paracetamol-induced hepatotoxicity when used concomitantly with N-acetyl cysteine.