Mechanisms of hepatoprotective effects of white and black garlic extracts against preneoplastic lesions induced by N-nitrosodiethylamine in rats

Introduction: Garlic has many pharmacological properties such as antibacterial, anti-inflammatory, and antioxidant activities. This study aimed to investigate the possible mechanisms of the hepatoprotective effect of white garlic extract (WGE) and black garlic extract (BGE) against preneoplastic lesions induced by N-nitrosodiethylamine (NDEA) in rats. Methods: Forty-two rats were randomly distributed into six equal groups. Oral administration of WGE and BGE began 3 weeks before injection of NDEA. Group 1 was kept as negative control, while the other groups were injected by a single intraperitoneal dose of NDEA in the 3rd week, followed by 2 subcutaneous injections/week of CCl4 till six weeks to induce preneoplastic lesions. Group 2 kept positive control and groups 3, 4, 5 and 6 were given WGE and BGE each of them at 250 and 500 mg/kg, respectively, for six weeks from the beginning. Serum liver enzymes, total protein, albumin (Alb), total bilirubin (TBil), and antioxidant enzymes were measured. Malondialdehyde (MDA), glutathione (GSH), tumor biomarkers, along with the content of 8-hydroxy-2-deoxyguanosine (8-OHdG) in liver DNA were estimated and liver histopathology was performed. Results: WGE and BGE significantly decreased the serum liver enzymes, TBil, tumor biomarkers, lipid peroxidation but increased total protein levels. The extracts significantly increased antioxidant enzymes, decreased 8-OHdG content in liver DNA, and alleviated histopathological lesions in the liver. Conclusion: The results affirm the hepatoprotective effect of WGE and BGE against NDEA-induced preneoplastic lesions in rats. This effect may be due to inhibition of lipid peroxidation, reduction of tumor biomarkers, enhancement of antioxidant enzymes, or reduction of 8-OHdG content in liver DNA.