Utilization of Antagonistic Interaction Between Micronutrients and Cadmium (CD) to Alleviate CD Toxicity and Accumulation in Crops

1. Introduction

Cadmium (Cd) is an unessential metal with no biological function and toxic to plants even at low concentrations (Haider et al. 2021). Many physiological dysfunctions will occur when plants are exposed to Cd stress, mainly leading to oxidative stress (Moradi et al. 2019). Oxidative stress is injurious and even lethal to plants, as it inhibits or disturbs physiological activities by altering membrane integrity and permeability at the organelle and molecular levels. Membrane damage will occur due to excessive generation of reactive oxygen species (ROS), such as superoxide anion (O₂⁻), hydroxyl radical (OH⁻), and hydrogen peroxide (H₂O₂) under Cd stress (Anjum et al. 2015). Moreover, Cd contamination in agricultural soils bring a huge threat to human health via a food chain, because Cd can induce several illnesses, including cancer, heart disease, vascular issues, kidney and liver damage, and disruptions to male reproductive system (Kumar and Sharma 2019) (Figure 1).

It is well documented that Cd uptake by roots from soils and transportation from roots to shoots (above ground organs) are dependent on the transporters of some nutrient ions that have the similar chemical and physical properties as Cd, such as Zn and Mn (Huang et al. 2020b). There is a dramatic difference in Cd accumulation among crop species, and genotypes within a species (Lin et al. 2022), which provides the possibility for developing crop cultivars with low Cd accumulation through genetic improvement or gene engineering. The physiological and molecular mechanisms of Cd uptake and transportation in plants have been intensively assessed to explain the distinct differences in Cd accumulation found across various species or genotypes. Cd and several micro-elements, including Mn, Zn, Cu, and Fe, interact antagonistically and synergistically in their plant uptake and transportation (Figure 1). Understanding the relationship between Cd and nutrient ions may offer evidence to explain the nature of Cd accumulation in crops (Mapodzeke et al. 2021).

Cd contamination has become a serious factor affecting sustainable crop production and human health via food chain. Hence, it is necessary to make major efforts to control Cd contamination in soil by cutting off entrance of Cd into agricultural ecosystems, phytoremediation of Cd-contaminated soil and reducing Cd bio-availability in soil. Meanwhile it is more important to develop the crop cultivars with high tolerance and low accumulation of Cd. In the past 20 years, numerous studies have examined the physiological and molecular mechanisms of Cd accumulation and detoxification in plants using genomics, transcriptomics, proteomics, and metabolomics, with an emphasis on identifying the genes responsible for Cd uptake, translocation, sequestration, and tolerance in plant tissues (Sterckeman and Thomine 2020). On the other hand, the plants with high tolerance and Cd accumulation can be used in phytoremediation of Cd contaminated soil. Naturally, certain plant species can accumulate a significant amount of Cd without experiencing any toxicity. It is well known that these plants have special tolerance mechanisms, such as compartmentalization, redox homeostasis maintenance, reducing rhizosphere Cd activity and Cd transfer to aboveground plant parts (Shiyu et al. 2020).

This review explores the complex interactions between cadmium (Cd) and essential micronutrients in plants, focusing on Cd uptake, transport, and detoxification mechanisms. By highlighting the roles of key transporters like OsZIP7, ATPase2, AtNRAMP3, and AtNRAMP4, the review provides insights into how Cd interacts antagonistically or synergistically with nutrients such as zinc (Zn), manganese (Mn), copper (Cu), and iron (Fe). Additionally, it examines genetic and agronomic strategies for reducing Cd accumulation in crops, emphasizing the potential for molecular and biochemical interventions to enhance crop tolerance to Cd toxicity.

2. Cd Uptake and Transport in Plants

2.1. Mechanisms of Cd Uptake by Roots

Cadmium (Cd) in soil is generally insoluble and not easily absorbed by plants. However, its bioavailability significantly increases when soil pH decreases, meaning that soil acidification can enhance Cd contamination. Plants can affect the bioavailability of cadmium (Cd) by releasing root exudates that alter the rhizosphere’s pH, which can strengthen Cd uptake. In addition, passive diffusion occurs for Cd entering plants through the apoplastic pathway, while the symplastic pathway, an active transport process, relies on electrochemical potential gradients and concentration differences across the plasma membrane (Bali et al. 2020, Thakur et al. 2016). For Cd absorbed by plant roots, it must be available for uptake, which is contingent upon the species of the plants, the physicochemical conditions of the soil, and the speciation of the metals (Rizwan et al. 2018). This metal is readily taken up by and delivered to the aerial portions of the plants (Shanmugaraj et al. 2019). The transfer of cadmium (Cd) from soil to grains is a complex and multi-stage process involving sequential mechanisms: initial uptake by roots, sequestration within root vacuoles to mitigate toxicity, subsequent translocation through the vascular system to aerial parts, and ultimate partitioning and accumulation in grains (Huang et al. 2020a). (Figure 2).

2.2. Role of Metal Transporters

In plants, metal transporters such as ZIP, NRAMP, and HMA families play pivotal roles in the uptake of essential micronutrients. However, these transporters can also facilitate the entry of non-essential and potentially toxic metals like cadmium (Cd) into root cells (Li et al. 2022). For instance, members of the ZIP family, including OsIRT1 and OsIRT2 in rice, are primarily responsible for iron and zinc uptake, but can inadvertently transport Cd due to its chemical similarity to these micronutrients. Similarly, NRAMP transporters, such as TcNRAMP3, are involved in the uptake of divalent cations like Fe²⁺ and Mn²⁺, yet they also permit Cd²⁺ entry into plant roots (Takahashi et al. 2011). The HMA family, particularly transporters like HMA2 and HMA4, is crucial for translocating essential metals; however, they can also contribute to Cd movement within the plants. This dual functionality underscores a significant challenge in plant nutrition and heavy metal detoxification, as the mechanisms that enable the acquisition of vital nutrients can simultaneously increase Cd accumulation, posing risks to plant health and food safety (Wong and Cobbett 2009).

2.3. Transporter Families Facilitating Cd Uptake and Transport

The transport of cadmium in rice (OsNramp5) and barley (HvNramp5) is mediated by Nramp5 homologs, which are also present in wheat (TaNramp5A, TaNramp5D) and maize (ZmNramp5). Nramp5, a Natural Resistance-associated Macrophage Protein family member, transports manganese and cadmium in plants (Palali Delen et al. 2024, Sui et al. 2018, Wu et al. 2016). OsNramp5 is localized at the distal edges of the exodermis in rice roots, facilitating Cd uptake, which is then either sequestered in vacuoles by OsHMA3 or transported to the shoots via the xylem. Cd competes with other divalent cations (Ca²⁺, Fe²⁺, Mg²⁺, Cu²⁺, Zn²⁺) for transport through root cell membranes, and its absorption varies significantly across plant species and genotypes due to morphological and physiological differences (Feng et al. 2021, Gupta et al. 2019, Ismael et al. 2019, Satoh-Nagasawa et al. 2012). Cd can enter plant roots from the soil solution through cell walls via passive transport. Additionally, active transport mechanisms involve nonspecific membrane transport proteins, such as iron transporters (IRT), zinc transporters (ZIP), and metal-pumping ATPases, which facilitate Cd movement across the plasma membrane of root cells. Other transporter families, including NRAMP, P-type ATPase, ABC transporters, CAX, LCT, and CE, have also been associated with Cd translocation within plants (Kim et al. 2015, Song et al. 2017). ZNT1 may be involved in the transport of Cd in the low Cd accumulation ecotype. At the same time, a high-affinity Cd transporter may also play a role in the transportation of Cd in the high accumulation ecotype.

2.4. Factors Influencing Cadmium Uptake in Plants

Cadmium (Cd) uptake in plants is intricately influenced by micronutrient nutrition, interactions with other metals, and the genetic and molecular machinery of plants. Micronutrients such as zinc (Zn) and iron (Fe) play pivotal roles in modulating Cd absorption, as they compete for transporters like ZIP proteins, often reducing Cd uptake when present in optimal concentrations (Rai et al. 2021) (Figure 2). Additionally, interactions with other metals, such as calcium (Ca) and magnesium (Mg), can alter membrane permeability and ion exchange, further influencing Cd transport (Rahman et al. 2016). Plant-specific genetic factors, including the diversity of metal transporter families like NRAMPs and HMA, regulate Cd uptake and sequestration in vacuoles or cell walls (Yadav et al. 2021). At the molecular level, transcription factors such as bZIP and MYB are critical in modulating gene expression for metal homeostasis, leading to variability in Cd accumulation among species and cultivars (Li et al. 2023b). Understanding this genetic and molecular diversity is crucial for breeding or engineering plants with reduced Cd uptake, ensuring safer agricultural production and mitigating heavy metal contamination in crops.

3. Genetic Regulation and Micronutrient-Cadmium Interaction

3.1. Genetic Regulation of Cd Uptake

Rice varieties display significantly genetic heterogeneity in Cd accumulation, offering a valuable resource for identifying functional alleles in improving Cd tolerance (Mei et al. 2022). Cd enters vacuoles for sequestration by a Cd transporter that is encoded by OsHMA3 (Ueno et al. 2010). The molecular mechanisms of toxic metal Cd in its transport and accumulation in plant tissues have been extensively studied in recent years, and appreciation of the massive amount of data has been offered by bio-informatic techniques, which have been applied extensively in a variety of plant species (Xu et al. 2020). These studies have shown the five groups into which the differentially expressed genes can be categorized, i.e., transporters, organic acids, metabolic pathways, phytohormones, and ROS generation (Angulo-Bejarano et al. 2021). Transcriptome sequencing revealed that higher Cd accumulation in Nicotiana tabacum leaves is driven by coordinated mechanisms, including reduced cell wall binding, weakened Casparian strip barriers, and enhanced xylem loading. Similarly, in barley, genes regulating ion transport, stress response, cell wall dynamics, and reactive oxygen species metabolism play crucial roles in Cd transport and tolerance (Huang et al. 2021c). Phytometallophores facilitate the transport of metals like Cd by binding to them during their passage through root cells, enabling efficient metal translocation (Singh et al. 2020).

3.2. Micronutrient-Cadmium Interaction in Their Uptake and Transport

Cadmium (Cd) enters plant cells via transporters typically involved in the uptake of essential micronutrients (Song et al. 2017). The uptake of Cd in plants is influenced by several essential elements such as calcium (Ca), copper (Cu), iron (Fe), zinc (Zn), and manganese (Mn) in the rhizosphere solution (Vítková et al. 2018). Cd poisoning often manifests as leaf chlorosis, resembling iron deficiency, as Cd affects iron accumulation essential for chlorophyll synthesis. It is showed that Cd stress reduces Fe uptake and its movement from roots to shoots. In Arabidopsis, increased iron availability reduces Cd uptake, whereas in peanuts, an iron deficit enhances Cd accumulation (He et al. 2017). The competitive relationship between Fe and Cd is further evident when phosphate or sulfate deprivation reduces Cd uptake by boosting Fe uptake (Yang et al. 2016). Moreover, different chelated forms of Fe, such as Fe (III) citrate, result in higher Cd accumulation than Fe (III) ethylenediaminetetraacetic acid (EDTA) (Gul et al. 2021). Mn has been found to reduce Cd uptake, as the two metals share similar absorption and transport pathways. Mn competes with Cd for uptake, and under Mn-replete conditions, plants exhibit increased antioxidant enzyme activity, high leaf Mn content, and improved photosynthetic efficiency, leading to alleviation of Cd toxicity, oxidative stress, and lipid peroxidation, likely due to Mn’s role as a cofactor in Mn-CAT and Mn-SOD enzymes (Leitenmaier and Küpper 2013, Sterckeman and Thomine 2020, Wang et al. 2018a). Zinc (Zn) and Cd interact in several ways due to their similar atomic structures, which complicates efforts to selectively reduce Cd uptake while maintaining Zn transport. Zn inhibits Cd uptake through shared transporters on the root plasma membrane, and it can mitigate oxidative stress and enhance plant growth (Kinnell 2019). Some studies suggest genotype-specific differences in Cd translocation, and Zn may help reduce Cd bioaccumulation in wheat (Zhou et al. 2020). Additionally, Zn Transporter7 (OsZIP7) and heavy metal ATPase2 (OsHMA2) are involved in the xylem loading of Zn and Cu in roots (Tan et al. 2019) (Figure 2).

Taken together, the interactions between essential nutrients and Cd uptake highlight the complexity of managing Cd toxicity in plants. Optimizing the balance of these elements can help mitigate Cd’s harmful effects, especially in crops like rice, wheat, and peanuts. Table 1 and Table 2 summarize with details of genes and their corresponding functions with identified crops.

4. Approaches for Alleviating Cd Toxicity and Accumulation in Crops

Cd toxicity and accumulation in crops are mainly controlled by genetic factors, but also heavily influenced by environmental (soil) conditions and agronomic practices. Hence, approaches of alleviating Cd toxicity and accumulation in crops are multifaceted, involving in genetic improvement for enhancing tolerance and reducing uptake and transport of Cd, soil remediation for reducing Cd content or bio-availability, and improvement of agronomic managements, including irrigation and fertilization for reducing Cd uptake.

4.1. Phytoremediation

An effective strategy for reducing Cd content in soil is bioremediation, a process that leverages the natural capabilities of plants, animals, and microorganisms to restore contaminated environments. Nowadays, phytoremediation of the contaminated soils by heavy metals, including Cd has been particularly highlighted and widely used because of its multiple advantages, such as low cost, no secondary contamination, and environmental friendly (Karami and Shamsuddin 2010, Raza et al. 2020). The application of Cd phytoremediation is mainly dependent on the availability of Cd hyperaccumulators, the plants with high Cd tolerance and root-to-shoot translocation of Cd. For instance, Noccaea caerulescens, is an extremophile heavy metal hyperaccumulator with a high capacity of Cd and Zn accumulation in shoots. It may be able to effectively phytoextract Cd from soils contaminated with Cd (Li et al. 2021). One factor contributing to Cd tolerance is the increased capacity of rhizosphere microorganisms to generate organic acid to chelate Cd²⁺ (Hou et al. 2018).

The effectiveness of Cd phytoremediation is significantly influenced by the balance and availability of essential soil micronutrients. Elements like Fe, Zn, and Mn affect Cd absorption by competing for uptake sites or modifying the bioavailability of metals (Li et al. 2023b, Raza et al. 2020). Factors such as soil pH, organic matter content, and microbial interactions further regulate the accessibility of these nutrients and Cd. Plants capable of efficiently absorbing and utilizing micronutrients tend to demonstrate higher tolerance and accumulation of Cd. Enhancing the levels and interactions of soil micronutrients is key to improving the success of phytoremediation efforts (Bali et al. 2020, Shahid et al. 2017).

4.2. Genetic Improvement

Genetic improvement represents a promising approach for mitigating cadmium (Cd) stress and toxicity in crop plants, addressing this critical issue from multiple angles. Advances in plant genetics allow for the development of cultivars with enhanced tolerance to Cd, achieved through various strategies such as the manipulation of Cd uptake and translocation pathways, increased sequestration and detoxification mechanisms, and enhanced repair and stress response systems. Key genetic modifications include the alteration of genes involved in Cd transport and binding, as well as the integration of traits that boost the plant’s ability to handle and detoxify heavy metals. Such improvements not only reduce Cd accumulation in edible plant parts but also enhance overall plant health and yield under contaminated conditions. These genetic strategies are crucial for developing crops that can thrive in Cd-contaminated soils, ensuring food safety and sustainability in agriculture (Li et al. 2017, Zhang et al. 2022).

In view of the fact that Cd enters roots and transports from roots to shoots via the transporters of some nutrient ions which have the similar physical and chemical properties with Cd, regulating expression of the genes encoding these ion transporters might be efficient to control Cd uptake and transport. Zinc (Zn), a crucial microelement for various plant enzymes, competes with Cd for binding sites on root surfaces and in soil, influencing Cd uptake in plants. Zinc-specific transporters, such as ZIP (zinc/iron-regulated transporter-like proteins), may inadvertently facilitate Cd entry into root cells and its subsequent redistribution throughout the plant. These Zn transporters, along with others from the IRT1, HMA2, HMA3, ZIP, and NRAMP families, play a key role in the uptake and translocation of Zn, Cd, and other ions (Zare et al. 2018). Modulating metal transporters provides an effective strategy to reduce Cd accumulation while preserving essential nutrient uptake. Silencing IRT1, which facilitates both Fe and Cd uptake, can limit Cd entry, but requires careful regulation to avoid disrupting Fe homeostasis (Ghorbani et al. 2024, Loix et al. 2017, Seth 2012). Overexpression of HMA3 enhances Cd sequestration into vacuoles, reducing its translocation to edible plant parts. These approaches balance nutrient acquisition with minimized Cd accumulation, offering potential for safer crop development and improved phytoremediation (Dendena 2012, Upadhyaya et al. 2023, Zhu et al. 2023).

There are multiple steps, from soil to grain, and a number of transporters involved. Thus, it is thought that one efficient way to lessen the amount of Cd that crops absorb is to breed low-grain cultivars that accumulate less Cd. This can be achieved through the use of transgenic technology. The main advantage of transgenic technology is the ability to efficiently express target genes in plants, giving them the correct genetic and biological traits, all without affecting crop quality or yield. For instance, low-Cd rice that accumulates less Cd can be produced without yield penalty by utilizing the CRISPR/Cas9 system to delete OsNramp5 (Songmei et al. 2019).

4.3. Agronomic Practices

A promising and cost-effective method to prevent cadmium (Cd) contamination in food involves using plant nutrients to mitigate Cd toxicity in crops (Nazar et al. 2012). Plants require a balanced supply of essential nutrients at optimal levels and timings to thrive and reduce Cd’s adverse effects. Farmers often enhance soil fertility to boost crop yields, but effective management of these nutrients is crucial for minimizing soil Cd toxicity. Understanding the interplay between essential plant nutrients and soil Cd is key to achieving this (Shiyu et al. 2020). Essential soil nutrients influence Cd availability and toxicity through both direct and indirect mechanisms (Zhang et al. 2019). These mechanisms include Cd sequestration in plant tissues, adsorption and precipitation in the soil, competition for membrane transporters, and prevention of Cd accumulation in grains and fruits, all of which work together to reduce Cd solubility and its impact on plant health (Dharma-Wardana 2018). The application of N and other nutrients can acidify the soil, which increases the solubility of Cd (Ning et al. 2017). Similarly, application of P fertilizer may have an impact on Cd solubility in soil (Noh et al. 2017). Fertilizers also determine the speciation of Cd, affecting Cd transport to roots and rhizosphere incorporation (Qaswar et al. 2017). The rhizosphere’s nutritional composition, root development, and overall plant growth are all impacted by fertilizer application (Wang et al. 2018b). Selenium (Se) applied at low concentrations to contaminated soil helps reduce Cd stress and promotes healthy plant growth (Gao et al. 2018).

Manganese (Mn) supplementation has been shown to mitigate cadmium (Cd) toxicity in plants by enhancing nutrient homeostasis and reducing Cd uptake. In maize seedlings, exposure to Mn alleviated Cd-induced root growth inhibition, with the degree of improvement correlating with Mn concentration (Choppala et al. 2014, Li et al. 2023a). Similarly, in rice seedlings, Mn application reduced Cd uptake and translocation, thereby improving growth and chlorophyll content under Cd stress. These findings suggest that Mn supplementation can enhance plant tolerance to Cd stress by modulating nutrient uptake and distribution (Huang et al. 2021a, Hussain et al. 2020, Shahzad et al. 2024).

Silicon (Si) also impacts Cd accumulation by modifying gene expression related to Cd uptake and sequestration. Si treatment is associated with the downregulation of Cd transporters, such as OsNRAMP5 and OsHMA2, and enhances the phytochelatin-driven compartmentalization of Cd in the vacuoles of rice roots. This interplay between Si and Cd management underscores Si’s role in mitigating Cd toxicity through complex biochemical and genetic mechanisms in agricultural practices(Bari et al. 2020). (Figure 3)

The chemical approach to reducing cadmium (Cd) uptake and transport in crops involves the application of foliar sprays or direct soil amendments, which utilize chelation or competition to inhibit Cd absorption. Silicon (Si) and selenium (Se) play a synergistic role in mitigating Cd toxicity by regulating gene expression, immobilizing Cd within root cell walls and organelles, and reducing its translocation to shoots (Huang et al. 2021b). The use of silicon-rich biochar or Si-fertilizers shows strong potential in further decreasing Cd uptake and movement within plants. Additionally, various other compounds and hormones have been identified as effective in minimizing Cd accumulation, offering a multifaceted strategy to combat Cd contamination in crops (Kapoor et al. 2023).

Applying micronutrient fertilizers, particularly those containing Zn and Mn, can effectively mitigate Cd uptake and accumulation in plants (Lv et al. 2019, Zhou et al. 2020). Foliar application of Mn and Zn has been shown to increase their concentrations in plant tissues, thereby enhancing nutrient content and potentially reducing Cd translocation to edible parts. Additionally, the interaction between Cd and Zn in the soil can influence their uptake and translocation within plants (Gupta et al. 2019, Riaz et al. 2021). By carefully balancing the application of these micronutrients, it is possible to enhance plant growth and reduce Cd accumulation, thereby improving food safety and crop quality.

5. Conclusions and Prospects

Cadmium (Cd) contamination poses a significant threat to crop productivity and food safety. While substantial progress has been made in understanding Cd absorption, transport, and resistance mechanisms in rice, critical gaps remain, particularly in the molecular regulation of vacuolar compartmentalization and cell wall sequestration of Cd. Future studies should focus on elucidating metabolic pathways altered under Cd stress and their interaction with plant nutrition.

Developing crop varieties with reduced Cd accumulation and enhanced tolerance, such as through the manipulation of transporters like OsNramp5 and OsHMA3, is a promising strategy. However, the functional roles of these transporters remain largely unexplored in crops other than rice and Arabidopsis. Bioremediation techniques, including phytoremediation, microbial remediation, and the use of biochar and organic amendments, also offer sustainable approaches for mitigating Cd toxicity in agricultural soils.

Emerging challenges, such as the impact of climate change on soil organic matter breakdown and Cd bioavailability, warrant further investigation. Additionally, identifying novel genes and understanding their roles in Cd uptake, transport, and detoxification will be critical for advancing sustainable agricultural practices and ensuring food safety in Cd-contaminated areas. Comprehensive research and innovative remediation methods are essential to mitigate Cd toxicity and improve crop yields in the face of environmental challenges.