Table 2.
Literature survey on hepatotoxicity by DCA in vivo.
| Experimental model | Treatment dose | Route of administration | Duration of treatment | Effect | Reference |
|---|---|---|---|---|---|
| Dogs | 300 mg/kg | Intravenously | 1 h | Decrease of tissue lactate levels in liver | (42) |
| B6C3F1 mice | 1–2 g/L | Drinking water | 52 weeks | Enlarged livers, cytomegaly, and glycogen accumulation | (43) |
| B6C3F1 and Swiss-Webster mice | 300–2000 mg/L | Drinking water | 14 days | Tumorigenesis is influenced by necrosis and reparative hyperplasia, increased 3H-thymidine labeling index | (44) |
| B6C3F1 mice | 200–600 mg/L | Drinking water | 72 h | Markedly enlarged liver, cytomegaly, glycogen accumulation, recurrent liver necrosis with high proliferation rates, peroxisome induction, and lipofuscin accumulation | (45) |
| B6C3F1 mice | 2.0 g/L | Drinking water | 38 or 50 weeks | Induction of hepatocellular lesions with increased cell divisions; increased c-Jun/c-Fos expression | (46) |
| B6C3F1 mice | 0.5 g/L | Drinking water | 2 weeks | 4-fold increase of in vitro colony formation of hepatocytes suggesting promotion of clonal expansion of anchorage-independent hepatocytes in vivo | (47) |
| B6C3F1 mice | 2 g/L | Drinking water | 48 weeks | Increase of tumor growth rates | (48) |
| B6C3F1 mice | 0.2–3 g/L | Drinking water | 4–12 weeks | Increase of glycogen concentration in liver | (49) |
| B6C3F1 mice | 0.1–2 g/L | Drinking water | 2–10 weeks | Reduction of serum insulin, downregulation of insulin receptor, and increased MAP kinase phosphorylation | (50) |
| B6C3F1 mice | 0.5 or 2 g/L | Drinking water | 35–52 weeks | Induction of liver tumors, which were c-Jun-positive | (51) |
| Fischer-344 rats | 0.05–20 mg/kg | Intravenously or by gavage | 7 days | Oral bioavailability was 0–13% in control rats and 14–75% in GSTZ-depleted rats | (52) |
| Sprague-Dawley rats | 2.5 μg–50 mg/kg/day | Drinking water | 12 weeks | GSTZ1-1 activity and expression decreased to 95–100% and recovered 8 weeks after cessation | (53) |
| B6C3F1 mice | 300 mg/kg | By gavage | 6 or 12 h | Increased production of superoxide anion, lipid peroxidation, and DNA-single strand breaks | (54) |
| B6C3F1 male mice | 7.7–410 mg/kg/day | By gavage | 4 or 13 weeks | Hepatomegaly at 410 mg/kg/day. Dose-dependent increase of SOD activity, lipid peroxidation, and DNA-single strand breaks | (55) |
| Sprague-Dawley rats | 500 mg/kg/day | By gavage | 8 weeks | Dechlorination of DCA was higher in cytosol than in mitochondria by GSTZ1 | (56) |
| PKD rats | 75 mg/L | Drinking water | 8 weeks | Only male rats with polycystic kidney disease (PKD) showed increased disease severity (cystic enlargement and proteinuria) | (57) |
| B6C3F1 mice | 7.5–30 mg/kg/day | By gavage | 13 weeks | Dose-dependent increase of SOD production, lipid peroxidation and DNA-single strand breaks | (58) |