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

Abstract

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.

The roles of catechins in regulation of systemic inflammation

“…Administration of catechins hydrate modulated benzo(a)pyrene-induced apoptotic toxicity and inflammation by regulating the expression of TNF-a, NF-jB, COX-2, BAX and caspase-3 in mice lung tissue (Shahid et al, 2016). Wang et al (2020) reported that EGCG helps the excretion of various heavy metals, including Hg, Cd, Cr, Ni, and Cu, absorbed into the body and reduces toxicity in tissues. Catechins have a high binding affinity with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins containing 3-chymotrypsin-like cysteine protease (3CL), RNA-dependent RNA polymerase (RdRp), and receptor-binding domain (RBD), so they have the potential to act as an excellent multi-targeting agent to regulate COVID-19 pandemic.…”

Heavy Metals in the Environment and Thyroid Cancer

“…Mathematical methodologies have been developed to estimate the consequences of the combined effect of chemicals: These conceptual models are mainly based on the assumption of either additive or independent actions, and they have been used to predict the mixture toxicity and to obtain some insight on the mechanisms associated with metal mixture [67][68][69]. These mathematical models, however, have limited practical applications because of the assumption that there is no interaction among the components of the mixture and because it is difficult to consider the relevance of the different chemical speciation of each metal present in the mixture [70].…”

Protective Effect of Wheat and Barley Grass Against the Acute Toxicological Effects of the Concurrent Administration of Excessive Heavy Metals in Drinking Water on the Rats Liver and Brain

“…The conditions for the digestion of MARS 6 classic were as follows: up to 180 • C for 25 min and then constant for 20 min, followed by a cooling stage (30 min) at 80 • C. Digested samples were diluted with ultrapure water after cooling to room temperature. These samples were used for the final heavy-metal element analysis, performed with an ICP-MS equipped with a concentric Nebulizer, a quartz torch with a quartz injector tube, and a cyclonic spray chamber [55].…”