Possible Protective Effect of Low-dose Gamma Irradiation and Certain Natural Products on Chemically Induced Hepatotoxicity in Rats

Liver, the largest organ in the human body, is a vital organ that performs more than 500 vital metabolic functions. More than a 1000 drugs of the modern pharmacopoeia can induce liver injury with different clinical presentations. In the most severe cases, drug-induced liver injury may require liver transplantation or lead to death of the patient. Acetaminophen (acetyl-para-amino-phenol, paracetamol, APAP) is safe at therapeutic doses, but accidental or intentional overdose can induce severe hepatotoxicity in both humans and experimental animals. APAP-induced hepatotoxicity is dose related and reproducible in animals, and is thus widely used as a model for experimentally induced hepatotoxicity. Many herbs have been used as natural remedies for the prevention and/or treatment of liver diseases. Herbal drugs gained importance and popularity in recent years because of their safety, efficacy and cost effectiveness. Interestingly, exposure to a small dose or dose rate of radiation was reported to induce stress, perturbing homeostasis. Organisms respond adaptively to such disturbances. The mechanisms by which low-dose radiation (LDR) protects the cells or tissue against subsequent radiation- or drug-induced toxicities have been attributed to its stimulation of various protective molecules such as antioxidants and anti apoptotic. In the light of the above mentioned information, this study was constructed in order to investigate the mechanism(s) of the hepato protective effects offered by each of garlic oil (GO), black seed oil (BO) and sesame oil (SO) each alone or combined with low dose total body gamma (γ)-irradiation against APAP-induced hepatotoxicity in male albino Wistar rats. Preliminary pilot studies were performed prior to the main experimental work; in order to select the effective irradiation dose, the hepato protective natural products and the duration of their administration to be used in the main study. To carry out the main study, 96 rats were randomly classified into 2 batches, one of which was subjected to irradiation and the other was kept non-irradiated. The non-irradiated batch was further subclassified into 6 groups. One group served as a normal group, the second group received APAP p.o (1 g/kg). The third, fourth and fifth groups were given either GO (100 mg/kg/day), BO (5 ml/kg/day) or SO (4 ml/kg/day) respectively, orally for 14 days before the induction of hepatotoxicity by APAP. The sixth group received N-acetyl cysteine (NAC, 0.39 g/kg) which was used as a reference hepato protective drug. The batch subjected to radiation was further subclassified into six groups. The first group was irradiated at a dose of 0.5 Gy. The second group received APAP dose 2 hours following irradiation at 0.5 Gy. The third, fourth, fifth and sixth groups were irradiated at 0.5 Gy, 90 minutes prior to the last treatment dose of either GO, BO, SO or the single NAC dose treatment, respectively. The four groups received APAP 30 minutes later. The animals were sacrificed by Summary and Conclusions cervical dislocation 24 hours following APAP treatment. Serum and liver tissue were used for biochemical analysis