*Purpose: ANG-3777 is a small-molecule mimetic of hepatocyte growth factor (HGF). In vitro models have shown ANG-3777 to have protective effects in renal cell lines, with the potential to improve renal function in acute kidney injury, such as occurs during renal transplantation or cardiac surgery requiring cardiopulmonary bypass. This study evaluates the effects of ANG-3777 on mercuric chloride (HgCl₂)-induced renal injury and mortalityin a rat model.

*Methods: In the first experiment to assess mortality, male Sprague-Dawley (SD) rats (n = 12 per group) were treated with 2.0 mg/kg intraperitoneal (IP) ANG-3777 or vehicle, exposed to high-dose IP HgCl₂ (5 mg/kg) within 1 hour of first dose, and then treated with a second dose of ANG-3777 or vehicle 18 hours later. Mortality was assessed at 24 hours post-first dose. In the second experiment to assess nephrotoxicity, SD rats were administered ANG-3777 IP (0.22, 0.66, 2, 4, or 12 mg/kg) or vehicle on Days 0 and 1. Low dose HgCl₂ (3 mg/kg, IP) was given on Day 1 at 1-hour after second ANG-3777 dose. On Day 2, a final treatment of ANG-3777 or vehicle was given (20 hours post-HgCl₂ and 4 hours prior to sacrifice). Serum creatinine and BUN were measured prior to sacrifice.

*Results: ANG-3777 (2.0 mg/kg) decreased HgCl₂-induced mortality in male SD rats: 33.3% (4 of 12) for ANG-3777 group vs 58.3% (7 of 12) for vehicle group. Administration of ANG-3777 at doses of 0.66 mg/kg to 12 mg/kg significantly decreased HgCl₂-induced renal impairment as measured by BUN and serum creatinine levels (p<0.0001) vs vehicle group (Fig 1).

*Conclusions: ANG-3777 reduced mortality in rats administered a high dose of HgCl₂ and significantly protected against renal dysfunction induced by low dose HgCl₂ in a dose dependent manner at IP doses ≥0.66 mg/kg. Beneficial effects of ANG-3777 in this in vivo test model of HgCl₂-induced nephrotoxicity suggest it may be a potential therapy for acute kidney injury.

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