Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl4; 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl4 significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 ± 1044%) and aspartate aminotransferase (AST; 6964 ± 833%), compared to control rats; CCl4 also significantly decreased serum concentration of albumin (23 ± 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 ± 33%). Furthermore, CCl 4 down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl4 produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl4: significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl4-treated rats; GbE partially prevented the increase of liver MDA (55 ± 14%) and the decrease of albumin concentration to 12 ± 0.2%. This pretreatment prevented the down-regulation of TNF-a and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl4-treated rats.
Low-dose nicotine self-administration is reduced in adult male rats naïve to high doses of nicotine: Implications for nicotine product standards.