Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Abstract

Objective: Monochloroacetic acid (MCA) is corrosive to skin, and causes not only chemical injury but also fatal systemic poisoning. Little is known about the cause of death. We studied the acute toxicity of MCA before clinical symptoms appeared in fasting rats. Methods: Blood samples were analyzed 2 h after subcutaneous MCA injection (LD 90 : 162 mg/ml kg body weight). Control rats were injected with saline. Results: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were about 1.5-fold higher than in the controls, and mitochondrial AST (mAST) was 2-fold higher. Blood urea nitrogen and creatinine were significantly increased, while serum glucose was significantly decreased in the treated group. Lactate was 6-fold higher and pyruvate was 13-fold higher than in the controls. Conclusions: MCA caused injury to the liver and kidneys but these injuries were slight. However, the larger increase in mAST indicated that hepatocellular mitochondria were selectively targeted. Hepatocellular mitochondrial injury decreased gluconeogenesis and caused hypoglycemia and extremely high levels of lactate and pyruvate. Hypoglycemia and lactic acidosis were insidious before the critical symptoms appeared and this combination accelerated to death, affecting other organs such as the heart and brain. Nosotropic therapy of these abnormalities up to the appearance of symptoms may help to establish an early therapy for skin exposure to MCA.

Effects of ruminal pH on gene expression in the rumen epithelium, peripheral blood mononuclear cell subpopulations, and blood metabolites from Holstein calves during weaning transition

“…Therefore, the higher levels of AST (68.8 vs. 78.7 IU/ l ), GGT (18.4 vs. 20.5 IU/ l ), and ALP (636.3 vs. 848.7 IU/ l ) observed at 3 weeks after weaning in the Starter group compared to Weaning group might imply decreased liver function caused by feeding a considerable amount of calf starter. Furthermore, disturbed liver function might induce lower glucose levels in the Starter group, which is consistent with hypoglycemia identified in an induced hepatic injury rat model [27]. Meanwhile, the Weaning group calves showed significant increases in T-CHO and PL at 3 weeks after weaning, and feeding calf starter without forage caused low peripheral TG, T-CHO, and PL concentrations in the present study.…”

Systemic effects and skin injury after experimental dermal exposure to monochloroacetic acid

“…The third grade chemical burn was caused despite the immediate water washing. He became unconsciousness after 90 min and died 6 h later in Japan, in 1999 (Toshina et al, 2004). Both the exposed area and the concentration of MCA in the clinical case were much more than the values of this study.…”

“…The progressive renal failure developed and he became anuria on the second day (Kulling et al, 1992). Increased lactic acid and pyruvic acid could result in metabolic acidosis in the former experimental studies (Dartsch et al, 2000;Toshina et al, 2004). Respiratory compensatation would likely decrease P CO2 and TCO 2 .…”

“…It would be resulted that the pH was kept within a normal range. AST, m-AST, ALT increased as a result of hepatocellular injuries and renal dysfunction consequently increased BUN and Cr in the MCA group (Toshina et al, 2004). MCA is known to cause severe damage to energy-rich tissues by interfering with the metabolism of fuel molecules of the tricarboxylic acid (TCA) cycle and glucogenesis (Saghir et al, 2001).…”

Lethal acute lung injury and hypoglycemia after subcutaneous administration of monochloroacetic acid

“…Hypoglycemia has been identified as a specific effect of MCA (Toshina et al, 2004b). The level of hypoglycemia at 2 h after 162 mg/kg MCA injection was not fatal.…”