Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity

Figure 5 Androstanol prevented CCl₄-induced hepatotoxicity. (A) CAR^+/+ or CAR^–/– mice were given a 100-mg/kg dose of CCl₄ by intraperitoneal injection, with or without pretreatment with androstanol (100 mg/kg). Serum ALT levels were measured 24 h later (n=6 per treatment group). Androstanol-pretreatment reduced the ALT level of CAR^+/+ mice to the level of CAR^–/– mice. An: androstanol. (B) Liver sections from the same animals 24 h after different treatments, as indicated, were stained with hematoxylin and eosin. (a) CAR^–/– mice, control; (b) CAR^+/+ mice, control; (c) CAR^–/– mice, androstanol; (d) CAR^+/+ mice, androstanol; (e) CAR^–/– mice, CCl₄; (f) CAR^+/+ mice, CCl₄; (g) CAR^–/– mice, androstanol plus CCl₄; and (h) CAR^+/+ mice, androstanol plus CCl₄. Androstanol pretreatment reduced the hepatic centrilobular necrosis in CAR^+/+ mice. Arrows indicate areas of hepatic necrosis. (C) The indices of centrilobular necrosis in CAR^+/+ mice and CAR^–/– mice. Androstanol-pretreatment reduced hepatic centrilobular necrosis of CAR^+/+ mice to the level of CAR^–/– mice. Data in (A) and (C) are mean±SD. (D) Hepatic mRNA level of drug-metabolizing enzymes with androstanol treatment. Total liver RNA was prepared from CAR^+/+ or CAR^–/– animals treated with a 100-mg/kg dose of androstanol by intraperitoneal injection (n=6 per treatment group) and subjected to PCR analysis with the indicated primers in Materials and methods. β-Actin mRNA level was also measured as an internal control. The amplified DNA was separated on a 1.5% agarose gel and visualized with staining by ethidium bromide. The expected sizes of the amplified cDNA are described in Materials and methods.