Joint Toxicity of a Multi-Heavy Metal Mixture and Chemoprevention in Sprague Dawley Rats

To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg•bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg•bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg•bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.