Impact of Multi-metal Mixture Administration Through Drinking Water on the Gut Bacterial Microflora and Oxidative Stress Parameters in Male and Female Mice

Background: Heavy metal containing wastes reaches to the food chain either directly or indirectly. These ingested toxic elements manifest direct impact on the gut ecosystem and its overall functioning. The present study explores the alteration in mice gut bacteria on exposure to mixture of toxic heavy metals through drinking water. Methods: Twelve experimental groups of Swiss albino male and female mice were exposed to the metal mixture of varying concentrations. Profiling of gut bacterial flora was done by periodical collection of fecal samples via culture-based technique. Redox status of all experimental animals was analyzed in blood samples collected on the day 30. Results: In comparison to the controls, nearly a 10-fold decline in colony forming units/ml was observed at higher modal concentrations (50× & 100×) at the end of 15 days, but 100-fold reduced bacterial count was recorded following 30 days of dosing. Sex specific significant alteration in the bacteria count and diversity was also observed. Overall experimental results showed a heavy metal dose-dependent decline in bacterial count and loss in diversity. Disturbance in the oxidative stress markers was recorded in response to high dose of metal mixture. In group receiving 100× dose, malondialdehyde levels were increased in the erythrocytes (P<0.05), and all of the other antioxidant parameters were decreased (P<0.05), except for reduced glutathione in both male and female mice. Conclusion: The present work is the first report on the multiple heavy metals induced gut microbiota alterations and its correlation to oxidative stress.

Combined Exposure to Metals in Drinking Water Alters the Dopamine System in Mouse Striatum

Environmental exposure to arsenic (As), lead (Pb), and cadmium (Cd) frequently occurs; however, data on the specific effects of combined exposure on neurotransmission, specifically dopaminergic neurotransmission, are lacking. In this study, motor coordination and dopamine content, along with the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors (DRs), were examined in the striatum of adult male mice following exposure to drinking water containing As, Pb, and/or Cd. We found that exposure to a metal mixture impaired motor coordination. After 4 weeks of treatment, a significant decrease in dopamine content and expression of TH, DAT, and VMAT2 was observed in the striatum of metal-mixture-treated mice, compared to the controls or single-metal-exposed groups. However, DRD1 and DRD2 expression did not significantly change with metal treatment. These results suggest that altered dopaminergic neurotransmission by the collective action of metals may contribute to metal-mixture-induced neurobehavioral disorders.

Hepatoprotective Effect of Costus Afer On Trace Metal Mixture Treated Rats Mediated By Regulation of Oxidative Stress Markers, Inflammatory Cytokines And Bio-Metal Chelation

Technological developments have led to exposure to various substances that are harmful to the environment and public health, including heavy metals. In the environment, these grades of metals are usually diverse mixtures shown to cause physiological, biochemical and neurological dysfunctions in humans and laboratory animals. Cadmium, Lead, and mercury have been envisaged to exhibit their hepatotoxic effects by oxidative induction damage and synthesis of reactive oxygen species (ROS). The current work evaluated the protective activity of aqueous leaf extract of Costus afer (ALECA)) on liver damage arsing from exposure to trace metal mixture (TMM): cadmium chloride (CdCl2), lead chloride (PbCl2), and mercury chloride (HgCl2). Five groups of weight matched Sprague Dawley rats were treated for 90 days. Metal mixture and deionized water were used to treat the 2 groups of rats whereas the other 3 groups were treated with various doses of the ALECA through oral gavage alongside the metal mixture. Hepatic function parameters, oxidative biomarkers, inflammatory cytokines, Morphological changes and trace metals (concentrations were monitored in the liver). TMM treatment resulted in significant increase in ALT, AST, ALP, bilirubin, IL-6, MDA, but decreased albumin, total protein, IL-10, SOD, CAT and GSH levels. TMM also caused some morphological changes and increased the heavy metal (Pb, Cd and Hg) concentrations in the liver. The leaf extract gave a reasonable protective effect on the hepatotoxicity caused by trace metal mixture - through the mechanisms of metal chelation, anti-inflammatory, and antioxidant although this depends on the dosage to the rats. ALECA may be beneficial in the management of liver toxicity.