title: Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in postnecrotic proliferative liver states.
authors.affiliation: Mirandeli Bautista, Ana María Téllez-López, Maricela López-Orozco, Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, CP 42000, México.
authors.forename: Mirandeli
authors.initials: M
authors.lastname: Bautista
authors.forename: María Ángeles Gómez
authors.initials: MÁ
authors.lastname: Del Rio
authors.forename: Juana
authors.initials: J
authors.lastname: Benedí
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Sánchez-Reus
authors.forename: José A
authors.initials: JA
authors.lastname: Morales-González
authors.forename: Ana María
authors.initials: AM
authors.lastname: Téllez-López
authors.forename: Maricela
authors.initials: M
authors.lastname: López-Orozco
keywords: Cell cycle; Dichloromethylene diphosphonate; Hepatotoxicity; Kupffer cells; Thioacetamide
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