Co-exposure to non-toxic levels of cadmium and fluoride induces hepatotoxicity in rats via triggering mitochondrial oxidative damage, apoptosis, and NF-kB pathways

• Published in: Environmental science and pollution research international 2020-07, Vol.27 (19), p.24048-24058
• Main Authors: Arab-Nozari, Milad, Mohammadi, Ebrahim, Shokrzadeh, Mohammad, Ahangar, Nematollah, Amiri, Fereshteh Talebpour, Shaki, Fatemeh
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; Aquatic Pollution; Atmospheric Protection/Air Quality Control/Air Pollution; BAX protein; Bcl-2 protein; Cadmium; Cadmium chloride; Carbonyl compounds; Carbonyls; Chemical and Drug Induced Liver Injury; Drinking water; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Environmental science; Exposure; Fluorides; Glutathione; Hepatotoxicity; IL-1β; Inflammation; Lipid peroxidation; Lipids; Liver; Male; Membrane potential; Mitochondria; NF-kappa B; NF-κB protein; Oxidation; Oxidation-Reduction; Oxidative Stress; Peroxidation; Pollutants; Rats; Reactive oxygen species; Research Article; Sodium fluoride; Superoxide dismutase; Toxicity; Tumor necrosis factor-α; Waste Water Technology; Water Management; Water pollution; Water Pollution Control
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1007/s11356-020-08791-4

Fluoride (F) and cadmium (Cd) are two common water pollutants. There is low information about their co-exposure in low doses. So, in this study, we evaluated the combination effects of non-toxic doses of F and Cd and the possible mechanism of their combined interaction. Male rats were exposed to non-toxic doses of sodium fluoride (30 mg/l) and/or cadmium chloride (40 mg/l) in drinking water for 6 weeks. Then, liver tissues were separated and several factors including oxidative stress, mitochondrial toxicity, inflammation, apoptosis, and biochemical and histopathological changes were evaluated. Cd and F alone did not induce any significant changes in evaluated factors compared to control group, while significant elevation in liver enzymes as well as histopathological changes were observed in rats treated with F+Cd. Also, a remarkable increase in oxidative stress markers including reactive oxygen species, lipid peroxidation, and protein carbonyl and also decreasing glutathione and superoxide dismutase levels were detected following co-exposure to F and Cd. Furthermore, a combination of F and Cd resulted in mitochondrial dysfunction, swelling, as well as a reduction in mitochondrial membrane potential in isolated liver mitochondria. On the other hand, TNF-α, IL-1β, and NF-kB inflammatory genes were upregulated in the liver after combined exposure to F and Cd compared to individual treatments. Also, F+Cd treatment increased the Bax expression but decreased the expression of Bcl-2 significantly. These findings suggest that Cd and F can potentiate their individual toxic effects on the liver tissue through disruption of the cellular redox status, inflammation, and apoptosis pathway.