Protein malnourishment: A predisposing factor in acrylamide toxicity in pregnant rats

Abstract

Exposure to acrylamide (3-10 mg/kg body weight) was found to be lethal for protein-deficient pregnant rats as evidenced by their increased mortality. It had no such effect on the normal protein diet fed pregnant and nonpregnant rats and the protein-malnourished nonpregnant rats. Protein deficiency during pregnancy caused a significant decrease in the activity of brain monoamine oxidase and acetylcholinesterase and striatal [3H]spiperone binding, known to label dopamine receptors; had no significant effect on the binding of 3H-QNB (quinuclidinyl benzilate) to cerebellar and [3H]diazepam to frontocortical membranes, known to label muscarinic and benzodiazepine receptors, respectively; and had no significant effect on brain glutathione (GSH) levels in comparison with pregnant rats fed normal protein diet. Exposure to acrylamide (2 mg/kg body weight) in protein-malnourished pregnant rats caused a marked decrease in the activity of monoamine oxidase and acetylcholinesterase and also in the binding of [3H]spiperone, [3H]QNB, and [3H]diazepam to striatal, cerebellar, and frontocortical membranes, respectively. Kinetic studies revealed that decreased binding of these ligands in the specific brain regions were due to decreased receptor sites (Bmax). A reduction in the brain glutathione content was also observed in these animals in comparison with those fed a low-protein diet during pregnancy. Pregnant rats fed a normal-protein diet on acrylamide exposure, however, showed no such biochemical changes in comparison with the pregnant rats fed normal protein diet. Also, no effect on any of the parameters studied was observed in the adult nonpregnant rats fed a low-protein diet (for 18 d) and those exposed to the monomer (d 6-17) fed either a normal- or low-protein diet in comparison with respective controls. The results indicate that pregnancy under conditions of malnutrition modifies the susceptibility of pregnant rats toward acrylamide.

Chemistry, Biochemistry, and Safety of Acrylamide. A Review

“…Although acrylamide caused toxicity in the pregnant mother, there was no evidence for acrylamide-induced neurotoxicity in the offspring of F1 males (214). Rats suffering from protein malnutrition were more susceptible to acrylamide toxicity than those on control diets (154). Otherwise, the roles of nutrients (proteins, carbohydrates, fats, vitamins, minerals) on the severity of acrylamide toxicity as well as possible additive and synergistic effects of heat-induced food mutagens and carcinogens and dietary acrylamide are largely unknown.…”

“…The GSH concentration in the human liver is high, ranging from 3 to 5 μmol/g of liver wet weight. Conditions that can decrease GSH levels and hence increase the toxicity of acrylamide at much lower exposure include (a) malnutrition associated with consumption of diets low in the sulfur amino acids cystine and methionine, which are needed for the synthesis of GSH ( , ); (b) oxidative stress, which may result in oxidation of GSH to GSSG; and (c) liver damage associated with alcoholic hepatitis, cirrhosis, and other malignant disorders (). The rate of protein synthesis as well as GSH levels of neuroblastoma cells decreased on exposure to acrylamide ( , ).…”