Toxicological studies of thallium in the rat with emphasis on biochemical, histopathological and ultrastructural changes

This research investigated the toxicology of the heavy metal thallium (Tl) with an emphasis on its effects on biochemical, histopathological, immunohistochemical and ultrastructural changes. The oral and intraperitoneal (ip.) route of administration of Tl both gave the similar values of LD₅₀ in rats which was found to be around 30 mg/kg Tl. Thallium is an extremely toxic metal. The symptoms of intoxication in rats included weakness, lethargy, loss of hair, diarrhea, ptosis of eyelids and respiratory difficulty. The toxic effects of Tl was dose-dependent. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased with increasing dose of Tl. The serum levels of ALT, AST and creatinine were increased in rats from the acute toxicity test which received a single dose of 30 mg/kg Tl (acute-Tl group) and even increased more in rats from the subacute toxicity test which were received 5 mg/kg Tl for 14 days by gavage (subacute-Tl group). Kidney was the organ which accumulated the highest content of Tl in both groups whereas brain accumulated the least.; Centrilobular necrosis was found in the liver of the acute-Tl group. Hepatocytes might be vacuolated. Shrunken glomeruli and tubular necrosis were present in the kidney of intoxicated rat. The secondary processes of podocytes became indistinct. The pathological changes in the subacute-Tl group were similar but appeared to be more severe. Frequent pyknosis and karyorrhexis were observed. Mitochondria swelled or lost cristae were the most common ultrastructural changes in Tl intoxication.; No pronounced necrosis was found in the brain of the acute-Tl group. Enzymes for neurotransmitter metabolism were affected. The activities of tyrosine hydroxylase (TH) and acetylcholinesterase (AChE) were inhibited while nitric oxide synthase (NOS) was enhanced. The lowered activity of TH in the corpus stratum in the acute-Tl group would decrease the production of catecholamines and affect the motor control of the intoxicated rats. Necroses in the cerebral cortex and cerebellum were more prominent in the subacute-Tl group. The number of Purkinje cells of the subacute-Tl group was less and gliosis was observed indicating damage in the brain. Neurofilaments were accumulated around the axon hillock and the initial segment of Purkinje cells. Axonal transport in the neurons were probably affected. Axonal degeneration, swollen mitochondria and vacuoles in neurons were the subcellular pathological changes.; Na+K+ATPase levels varied in different regions of the rat brain, the levels followed the order: cerebral cortex > cerebellum > thalamus > hypothalamus > pons in the brains of the control group (0 mg/kg Tl). In the brains of the acute-Tl group the order has a slight difference: cerebellum > cerebral cortex > thalamus > hypothalamus > pons. There was an overall inhibition of brain Na+K+ATPase after Tl exposure. The levels decreased to 29–64% of the levels of the control group. The inhibition might cause osmotic imbalance and metabolic disturbances of neurons.; Prussian blue (PB) was more effective in protecting rats from Tl intoxication than EDTA, DMSA and DTPA. The mortality was lowest in rats received PB. The Tl contents in the kidney, stomach, ileum and cerebrum were decreased after feeding PB, ALT, AST and creatinine levels were also decreased. Necroses in the liver and kidney were not so serious in PB treated rats. Recovery of the liver and kidney probably resulted after treatment with PB.