Published online Jul 27, 2013. doi: 10.4254/wjh.v5.i7.379
Revised: June 17, 2013
Accepted: June 18, 2013
Published online: July 27, 2013
Processing time: 117 Days and 2 Hours
AIM: To study the effect of dichloromethylene diphosphonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA).
METHODS: Rats, intravenously (iv) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mechanisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract.
RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration.
CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in postnecrotic proliferative liver states.
Core tip: Over the last 20 years, liposomes, useful models for cell membranes, have become a powerful research tool whose study has resulted in many advances in cell physiology. When encapsulated in liposomes, dichloromethylene diphosphonate, a selective Kupffer cell toxicant, completely eliminates large Kupffer cells from the liver, allowing us to elucidate the role of these macrophages in total damage induced by hepatotoxic compounds such as thioacetamide.