Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine

Abstract

Chronic ingestion of environmental heavy metals such as lead (Pb) and cadmium (Cd) causes various well-documented pathologies in specific target organs following their intestinal absorption and subsequent accumulation. However, little is known about the direct impact of the non-absorbed heavy metals on the small intestine and the colon homeostasis. The aim of our study was to compare the specific bioaccumulation and retention of Cd and Pb and their effect on the essential metal balance in primary organs, with those occurring specifically in the gastrointestinal tract of mice. Various doses of Cd (5, 20 and 100 mg l(-1)) and Pb (100 and 500 mg l(-1)) chloride salts were provided in drinking water for subchronic to chronic exposures (4, 8 and 12 weeks). In contrast to a clear dose- and time-dependent accumulation in target organs, results showed that intestines are poor accumulators for Cd and Pb. Notwithstanding, changes in gene expression of representative intestinal markers revealed that the transport-, oxidative- and inflammatory status of the gut epithelium of the duodenum, ileum and colon were specifically affected by both heavy metal species. Additionally, in vivo comet assay used to evaluate the impact of heavy metals on DNA damage showed clear genotoxic activities of Cd, on both the upper and distal parts of the gastrointestinal tract. Altogether, these results outline the resilience of the gut which balances the various effects of chronic Cd and Pb in the intestinal mucosa. Collectively, it provides useful information for the risk assessment of heavy metals in gut homeostasis and further disease's susceptibility.

Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome

“…In an earlier study, these HM levels were sub-toxic and not associated with hepatotoxicity or changes in behavior, organ weights (liver, spleen and kidneys), body weight or overall growth (when compared with regular water-treated mice, [11]. Furthermore, none of the HM treatments had a detectable impact on our animals’ food intake, stool consistency or gut motility.…”

“…The metals were administered continuously for 8 weeks by spiking the animals’ drinking water with CdCl 2 or PbCl 2 solution, as previously described [11]. In order to cover both “environmentally relevant (low)” and “critical” doses of Cd exposure and to mimic Pb poisoning, the HM doses were selected according to the respective “lowest observed adverse effect” level (LOAEL) for chronic exposure in rodents.…”

GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney

“…The chronic ingestion of Pb causes various well-documented pathologies in the kidney following its intestinal absorption and subsequent accumulation [20]. …”

Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

“…As shown in Table 2, the mice were randomly divided into five groups (10) SM ϩ Cd Cd ϩ 8610 (10) SM ϩ CCFM8610 ϩ Cd Cd ϩ 11 (10) SM ϩ CCFM11 ϩ Cd Cd ϩ 8614 (10) SM ϩ CCFM8614 ϩ Cd a SM, 0.5 ml of skim milk once daily via gavage; PW, plain water for drinking; Cd, CdCl 2 at 100 mg/liter in drinking water; SM ϩ CCFM8610 (or CCFM8611 or CCFM8614), 1 ϫ 10 9 CFU L. plantarum CCFM8610 (or CCFM8611 or CCFM8614) in 0.5 ml of skim milk once daily via gavage. The treatments lasted 8 weeks.…”

“…For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain (4); therefore, the intestinal tract is the first organ that is susceptible to Cd contamination. Early in vitro and animal studies have shown that the intestinal barrier plays a crucial role in limiting Cd absorption (5,6), and Cd exposure causes an inflammatory response, death of epithelial cells, and damage to tight junctions in the intestines, leading to the disruption of the intestinal barrier and the amplification of Cd absorption (6)(7)(8)(9)(10). A recent research study also revealed that subchronic oral Cd exposure significantly affects the gut ecology and susceptibility to colitis in mice (11).…”