Cadmium (Cd) is a pervasive environmental and industrial toxin that poses significant health risks. It readily moves through soil–plant systems, leading to global contamination and human exposure through diet, smoking, and pollution. The main purpose of this review is to explore the effect of Cd on physiological processes of different bodies’ organs, including the bones, kidneys, and liver, as well as the immune, cerebrovascular, cardiovascular, and reproductive systems. Accumulation of Cd in the body can result in poisoning with severe impacts on bone and kidney health, as well as reduced bone mineral density due to renal damage. Research has linked Cd to lung cancer and pulmonary toxicity, and elevated urinary biomarkers suggest compromised renal function. Cd also affects the cardiovascular, cerebrovascular, and immune systems; the liver; and reproductive systems, contributing to various diseases by disrupting blood pressure and calcium regulation, causing oxidative stress and DNA damage, and impairing cell functions. Ongoing research is essential to fully understand Cd-induced toxicological effects and to develop effective interventions to prevent exposure and mitigate health risks.

Chickens are a major source of meat and eggs in human food and have significant economic value. Cadmium (Cd) is a common environmental pollutant that can contaminate feed and drinking water, leading to kidney injury in livestock and poultry, primarily by inducing the generation of free radicals. It is necessary to develop potential medicines to prevent and treat Cd-induced nephrotoxicity in poultry. Luteolin (Lut) is a natural flavonoid compound mainly extracted from peanut shells and has a variety of biological functions to defend against oxidative damage. In this study, we aimed to demonstrate whether Lut can alleviate kidney injury under Cd exposure and elucidate the underlying molecular mechanisms. Renal histopathology and cell morphology were observed. The indicators of renal function, oxidative stress, DNA damage and repair, NAD⁺ content, SIRT1 activity, and autophagy were analyzed. In vitro data showed that Cd exposure increased ROS levels and induced oxidative DNA damage and repair, as indicated by increased 8-OHdG content, increased γ-H2AX protein expression, and the over-activation of the DNA repair enzyme PARP-1. Cd exposure decreased NAD⁺ content and SIRT1 activity and increased LC3 II, ATG5, and particularly p62 protein expression. In addition, Cd-induced oxidative DNA damage resulted in PARP-1 over-activation, reduced SIRT1 activity, and autophagic flux blockade, as evidenced by reactive oxygen species scavenger NAC application. The inhibition of PARP-1 activation with the pharmacological inhibitor PJ34 restored NAD⁺ content and SIRT1 activity. The activation of SIRT1 with the pharmacological activator RSV reversed Cd-induced autophagic flux blockade and cell injury. In vivo data demonstrated that Cd treatment caused the microstructural disruption of renal tissues, reduced creatinine, and urea nitrogen clearance, raised MDA content, and decreased the activities or contents of antioxidants (GSH, T-SOD, CAT, and T-AOC). Cd treatment caused oxidative DNA damage and PARP-1 activation, decreased NAD⁺ content, decreased SIRT1 activity, and impaired autophagic flux. Notably, the dietary Lut supplement observably alleviated these alterations in chicken kidney tissues induced by Cd. In conclusion, the dietary Lut supplement alleviated Cd-induced chicken kidney injury through its potent antioxidant properties by relieving the oxidative DNA damage-activated PARP-1-mediated reduction in SIRT1 activity and repairing autophagic flux blockade.

Our previous studies have confirmed that cadmium (Cd) exposure causes hepatotoxicity; it also induces autophagy and blocks the autophagy flux. Therefore, we hypothesized that Cd hepatotoxicity could be alleviated through nutritional intervention. Taurine (Tau) has various biological functions such as acting as an antioxidant, acting as an anti-inflammatory, and stabilizing cell membranes. In order to explore the protective effect and internal mechanism of Tau on Cd-induced hepatotoxicity, normal rat liver cell line BRL3A cells were treated with Cd alone or in combination with Tau to detect cell injury and autophagy-related indexes in this study. We found that Tau can alleviate Cd-induced cell-proliferation decline and morphological changes in the cell. In addition, Tau activates autophagy and alleviates the blockage of Cd-induced autophagy flux. In this process, lysosome acidification and degradation were enhanced, and autophagosomes were further fused with lysosomes. Then, we found that Tau alleviated autophagic flux block by promoting the transfer of membrane fusion proteins STX17 and SNAP29 to autophagosomes and the translocation of VAMP8 to lysosomes, which in turn attenuated the hepatocyte injury induced by Cd exposure. This will further reveal the hepatotoxicity mechanism of Cd and provide the theoretical basis for the prevention and treatment of Cd poisoning.

Cadmium (Cd) is a major health concern globally and can accumulate and cause damage in the liver for which there is no approved treatment. Baicalin and N-acetylcysteine (NAC) have been found to have protective effects against a variety of liver injuries, but it is not clear whether their combined use is effective in preventing and treating Cd-induced lipid accumulation. The study found that Cd increased the production of mitochondrial reactive oxygen species (mROS) and elevated the level of chaperone-mediated autophagy (CMA). Interestingly, mROS-mediated CMA exacerbates the Cd-induced inhibition of lipophagy. Baicalin and NAC counteracted inhibition of lipophagy by attenuating Cd-induced CMA, suggesting an interplay between CMA elevation, mitochondrial destruction, and mROS formation. Maintaining the stability of mitochondrial structure and function is essential for alleviating Cd-induced lipid accumulation in the liver. Choline is an essential component of the mitochondrial membrane and is responsible for maintaining its structure and function. Mitochondrial transcriptional factor A (TFAM) is involved in mitochondrial DNA transcriptional activation and replication. Our study revealed that the combination of baicalin and NAC can regulate choline metabolism through TFAM and thereby maintain mitochondrial structure and functionality. In summary, the combination of baicalin and NAC plays a more beneficial role in alleviating Cd-induced lipid accumulation than the drug alone, and the combination of baicalin and NAC can stabilize mitochondrial structure and function and inhibit mROS-mediated CMA through TFAM-choline, thereby promoting lipophagy to alleviate Cd-induced lipid accumulation.

Cadmium accumulation in the body can damage a variety of organs and impair their development and functions. In the present study, we investigated the effect of cadmium on the stemness and proliferation of normal bovine mammary epithelial cells (BMECs). Normal bovine mammary epithelial cells treated with cadmium chloride were assessed for the expression of stemness-related proteins and cell proliferation. Western blotting results found that exposure to different concentrations of cadmium (0, 1.25, 2.5, and 5 μm) for 48 h significantly increased Gli1 expression but unexpectedly decreased the expression of downstream stem cell-related proteins including BMI1, SOX2, and ALDH. However, we also observed that treatment with 5 μm cadmium for 48 h inhibited mammosphere formation using microscopy. In this study, cadmium exposure significantly reduced cell viability and mobility. Flow cytometry detection found that cadmium decreased the percentage of cells in the G0 phase but increased the percentage of cells in the S phase and the apoptosis rate. Furthermore, cadmium exposure significantly increased the levels of caspase-8, caspase-3, and PARP cleavage as assessed by western blotting. Our study uncovers a previously unrecognized role of cadmium in mammary cell stemness and suggests that cadmium may affect breast development by impairing normal stem cell self-renewal and inducing their apoptosis. Therefore, this study provides important scientific significance regarding whether heavy metal cadmium affects normal breast development.