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

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.

Log-normal distribution of the trace element data results from a mixture of stocahstic input and deterministic internal dynamics.

In previous article, we showed a log-normal distribution of boron and lithium in human urine. This type of distribution is common in both biological and nonbiological applications. It can be observed when the effects of many independent variables are combined, each of which having any underlying distribution. Although elemental excretion depends on many variables, the one-compartment open model following a first-order process can be used to explain the elimination of elements. The rate of excretion is proportional to the amount present of any given element; that is, the same percentage of an existing element is eliminated per unit time, and the element concentration is represented by a deterministic negative power function of time in the elimination time-course. Sampling is of a stochastic nature, so the dataset of time variables in the elimination phase when the sample was obtained is expected to show Normal distribution. The time variable appears as an exponent of the power function, so a concentration histogram is that of an exponential transformation of Normally distributed time. This is the reason why the element concentration shows a log-normal distribution. The distribution is determined not by the element concentration itself, but by the time variable that defines the pharmacokinetic equation.

Therapeutic effects of glucose infusion on monochloroacetic acid exposure in rats.

The effects of glucose infusion on monochloroacetate (MCA) exposure were examined in male rats with a view toward effective clinical treatment for MCA intoxication. Rats were injected with 80 mg/kg sodium monochloroacetate (SMCA) (single lethal dose) and then infused with saline (control group) or 5% or 10% glucose solution at 2 mL/hour for ten hours. No animal in the control group survived the total 14-day follow-up period. The survival rate in 5% glucose group was 57% at ten hours; it decreased to 14% at 14 days. The survival rate in 10% glucose group was 79% at ten hours, and all rats that survived the first ten hours also survived the 14 days. Kaplan-Meier analysis showed the survival rate in 10% glucose group to be improved upon in both the 5% glucose group and the control group. Blood glucose and lactate levels were measured every hour during infusion. Blood glucose levels decreased in the control group but remained in the glucose-infused groups. Although the blood lactate level increased in each group, there was an excellent inverse linear relation between blood glucose levels and blood lactate levels. Thus, continuous parenteral infusion of glucose solution at an early stage after exposure may be an effective clinical therapy for the prevention of hypoglycaemia and metabolic lactic acidosis caused by MCA.