Metabolic studies of HgCl2-induced acute renal failure in the rat

HgCl₂ was used to produce acute renal failure (ARF) in rats. It caused significant decreases (P < 0.001) in ATP, ADP, and total adenine nucleotide levels to 50% of controls at 48 hr with no change in AMP levels. Lactate increased to threefold control levels at 6 hr and remained significantly elevated (P < 0.001) at 48 hr. At 24 hr, there was widespread necrosis in the pars convoluta and pars recta. At 48 hr, necrosis was accompanied by some regeneration, and creatinine levels exceeded 5 mg/dl. Dithiothreitol (30.8 mg/kg, ip, 30 min after HgCl₂) partially ameliorated the functional lesion (creatinine levels ?3.6 mg/dl) and resulted in reduced necrosis in the pars convoluta, but did not significantly alter the metabolic pattern. The results indicate an early metabolic disturbance and are consistent with the idea that HgCl₂ exerts a direct action on the enzymes of the mitochondrial electron transport chain. The failure of dithiothreitol to alter the metabolic pattern of HgCl₂-induced ARF indicated that its protective effect was probably not mediated directly through the maintenance of adenine nucleotide levels.