Long-term exposure to Cd through contaminated food can lead to multiple adverse health effects on humans. Although previous studies have covered global food Cd concentrations and dietary Cd exposures across different populations, there are increasing concerns regarding the adequacy of current food Cd safety standards to protect populations from adverse health effects. Moreover, incorporation of Cd relative bioavailability (Cd-RBA) in foods improves the accuracy of health risk assessment. However, factors influencing food Cd-RBA have not been systematically discussed, thereby hindering its application in risk assessment. This review aims to provide an overview of Cd contents in foods, discuss concerns regarding international food Cd concentration standards, explore factors influencing food Cd bioavailability, and highlight the opportunities and challenges in refining differences between dietary Cd intakes and body burdens. Our findings suggest that current safety standards may be insufficient to protect human health, as they primarily focus on kidney damage as the protective endpoint and fail to account for global and regional variations in food consumption patterns and temporal changes in dietary habits over time. Factors such as crop cultivars and food compositions greatly influence food Cd-RBA. To improve the accuracy of Cd health risk assessment, future studies should incorporate food Cd-RBA, sociodemographic characteristics, nutritional status, and incidental Cd exposure. This review highlights new insights into food Cd safety standards and Cd bioavailability, identifies critical knowledge gaps, and offers recommendations for refining health risk assessments. This information is essential to inform future bioavailability investigations, health risk assessment, and safety standard development.

Atrazine (ATR), a widely used herbicide, poses significant environmental and health risks due to its high solubility and adsorption in soil. ATR exposure can lead to nephrotoxicity in humans and animals. Curcumin (Cur), an active compound in Curcuma species, is renowned for its antioxidant and anti-inflammatory properties, with potential to mitigate chronic disease risks. We hypothesized that the addition of Cur could alleviate renal impairment associated with ATR exposure and carried out experiments using mice as subjects. This study investigates whether Cur can attenuate ATR-induced nephrotoxicity in mice by modulating mitophagy and apoptotic pathways. Our findings illustrate that consumption with Cur attenuates nephrotoxicity induced by ATR, as evidenced by lowered serum concentrations of uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE), established biomarkers of renal injury. Moreover, Curcumin enhances renal antioxidant defense mechanisms in ATR-exposed mice, as indicated by elevated levels of total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-Px), alongside reduced levels of malondialdehyde (MDA). Histopathological and electron microscopy analyses further corroborate these findings, showing reduced organelle damage, particularly mitochondrial ridge breakage and vacuolization, and increased autophagic lysosomes. Cur further enhances PINK1/Parkin-mediated autophagy, as evidenced by elevated levels of PINK1, Parkin, LC3BII, and P62 compared to ATR-treated mice. Moreover, Cur mitigates the mitochondrial apoptotic pathway, indicated by the down-regulation of apoptosis-related genes (Cytochrome C (Cyto-C), Caspase3, Caspase9) and the proapoptotic marker (Bax), along with the up-regulation of the anti-apoptotic marker (Bcl-2) at both transcriptional and translational levels compared to ATR-treated mice. In summary, Cur demonstrates nephroprotective properties against ATR-induced injury through the enhancement of mitochondrial autophagy and display of antiapoptotic actions, underscoring its curative potency as a treatment for nephrotoxicity caused by ATR.

Micro/Nano plastics (MNPs) pollutants are widespread in the environment, raising significant concerns about their biosafety. Emerging studies indicate that the urinary system is a primary accumulation site for MNPs, leading to severe tissue and functional damage. This review aims to summarize recent research on the potential hazards that MNPs may pose to the urinary system, highlighting the mechanisms of toxicity and the current state of knowledge. Studies have shown that MNPs enter the human body through drinking water, the food chain, inhalation, and skin contact. They may penetrate the bloodstream via the digestive, respiratory, and skin systems, subsequently dispersing to various organs, including the urinary system. The potential accumulation of MNPs in the urinary system might induce cellular oxidative stress, inflammation, apoptosis, autophagy, the intestine-kidney axis, and other possible toxic mechanisms. These processes could disrupt kidney metabolic functions and promote tissue fibrosis, thereby potentially increasing the risk of urinary system diseases. Despite ongoing research, the understanding of MNPs' impact on the urinary system remains limited. Therefore, this review provides a comprehensive overview of MNPs' potential toxicity mechanisms in the urinary system, highlights key challenges, and outlines future research directions. It offers a theoretical basis for the development of effective protective measures and policies.

Cadmium (Cd) exposure in humans primarily occurs through dietary intake, with conventional one-compartment toxicokinetic (TK) models linking dietary Cd intake to urinary Cd (UCd) levels, predominantly in Western populations with low background exposure. However, the applicability of this model to regions with high dietary Cd intake, particularly from rice consumption, remains uncertain. In this study, we conducted a comprehensive population-based survey involving 686 individuals from a typical Cd-polluted area and 296 from a non-polluted area in China, where rice serves as the staple food in both regions. Additionally, we selected 34 individuals from the polluted area for a 27-month intervention, during which home-grown high-Cd rice was replaced with low-Cd rice available in the market. We closely monitored temporal changes in Cd concentration and stable isotope signatures in urine samples. The adults in the polluted area had much higher dietary Cd intakes (mean 58.5 mu g kg-1 body weight month-1) and UCd (geometric mean 6.1 mu g g-1 creatinine) than those in the non-polluted area. There was a robust dose-response relationship (R2 = 0.67, n = 982) between UCd and beta 2-microglobulin, a biomarker of renal tubular impairment. The intervention reveals that a considerable proportion of Cd rapidly exuded after recent dietary intake, contradicting the conventional TK model. The modified TK model incorporating the direct blood-urine allocation greatly improved the association between dietary Cd intake and UCd. These results underscore the potential for high dietary Cd intake through rice in China to cause dose-dependent kidney damage. The modified TK model offers a reliable framework to estimate Cd-related thresholds and associated health risks for populations reliant on rice-based diets.

Mesoamerican nephropathy (MeN) is a non-traditional chronic kidney disease in some areas of Mesoamerica. The health risk from nephrotoxic metals, such as arsenic (As), lead (Pb), mercury (Hg), vanadium (V), cadmium (Cd), rubidium (Rb), chromium (Cr), and nickel (Ni), was assessed in drinking water and soils. These metals, even at low concentrations, have the capacity to induce epigenetic damage and a nephrotoxic effect. The quantification of metals in soils was made through X-ray fluorescence spectrometry (XRF) and inductively coupled plasma optical emission spectrophotometry (ICP-OES), while the quantification of metals in water was carried out through inductively coupled plasma mass spectrometry (ICPMS) and atomic absorption (AA) spectrometry. The levels of As, Hg, Cd, and V in water were within the permissible limits, whereas Pb was found to be double and triple the value recommended by the World Health Organization. The non-carcinogenic risk from As in soil was evaluated using the Hazard Index (HI), and the route of ingestion was found to be the most important route. The results indicate that consuming water or ingesting soil particles with Pb and As poses a health risk to humans. Therefore, these findings identify the presence of toxicants in an exposure scenario and justify further research into these metals in people and the analysis of exposure routes.

alpha -Tocopherol's (Vitamin E) antioxidant and anti-inflammatory properties may help reduce the progression of fibrosis in kidney by limiting tissue damage and inflammation induced by arsenic. Knowledge of the mechanisms of action of natural medicinal substances in arsenic toxicity will be improved by the analysis of the ameliorative effects of alpha -tocopherol. The goal of the current investigation was to determine whether Vitamin E can protect rats from nephrotoxicity caused by sodium arsenite (NaAsO2). Twenty-five Wistar rats were split into five groups viz: Group I with distilled water as control; Group II -IV with 8.4 (Low dose)/12.3 (Moderate dose)/16.4 mg/kg NaAsO2 (High dose); and Group V as in Gr. IV + 50 mg/kg alpha -Tocopherol. Both the doses were administered orally to rats for 60 days. alpha -tocopherol decreased the concentration of serum parameters like urea nitrogen (UN) and creatinine (CRT) whereas increased the concentration of albumin (ALB), acid phosphatase (ACP), alkaline phosphatase (ALP) and succinic dehydrogenase (SDH) ( P <0.05). In comparison to control group, the transcript levels of p53 were significantly higher in the LDG, MDG, and HDG rats, respectively, by -0.7 fold, -0.4 fold, and -0.5 fold. Similar to this, p21 transcript levels were higher in LDG, MDG and HDG groups than in those from the control group by -0.2 fold, -0.4 fold and -0.6 fold, respectively. Additionally, as compared to rats in the control group, the levels of p27 transcripts were decreased by -0.5 fold, -0.5 fold, and -0.4 fold in the LDG, MDG, and HDG rat populations, respectively. Co -administration of alpha -tocopherol with NaAsO2 showed decreased mRNA expression of p53 and p21 followed by increased mRNA expression of p27. In this investigation, it was discovered that alpha -tocopherol had a protective effect against renal damage brought on by NaAsO2.

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long-term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B-Se) and urine selenium (U-Se) levels were detected in these areas, measuring 416.977 mu g/L and 352.690 mu g/L and 104.527 mu g/L and 51.820 mu g/L, respectively. Additionally, the median blood Cd (B-Cd) and urine Cd (U-Cd) levels were markedly elevated at 4.821 mu g/L and 3.848 mu g/L and at 7.750 mu g/L and 7.050 mu g/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 mu mol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 mu mol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent. Se is an essential trace element for humans. However, excessive intake of Se can harm humans. Cd is a carcinogen and a chronic potent nephrotoxin that mostly accumulates in the human liver and kidneys. Animal experiments suggest that Se may alleviate Cd toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale exposure have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. Our results suggested that the exposed black shale areas are simultaneously enriched with Se and Cd. However, residents in these areas were exposed to excessive Se and Cd long-term without significant damage to liver and kidney functions. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. The risk assessment of heavy metals in high-Se geological background areas cannot be separated from human health surveys. Our study provides evidence for the antagonistic effects of Se and Cd on the human body. Residents in exposed black shale areas consume excessive Se and Cd through local rice Human liver and kidney functions are not significantly damaged in exposed black shale areas The USEPA method may not accurately assess Cd risk in exposed black shale areas

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.