IntroductionHeavy metals, like cadmium, lead, and arsenic, harm air, soil, agriculture, and human health. Plants suffer from reduced growth, chlorophyll production, and enzyme activity due to heavy metal exposure. Reactive oxygen species are produced, damaging biological molecules. However, plants have developed resistance mechanisms, including antioxidant stimulation. Flavonoids, complex compounds in plants, enhance resistance to heavy metals. Medicinal plants, rich in secondary metabolites like flavonoids, phenolic compounds, and alkaloids, show resistance to heavy metals. Origanum majorana as a medicinal plant, contains compounds that contribute to its heavy metal resistance. Based on limited studies, medicinal plants, particularly marjoram, have shown greater resistance to environmental stresses due to their secondary metabolites and the ability to produce uncontaminated essential oils in response to heavy metals like cadmium and lead. This study aimed to investigate the biochemical responses and growth of marjoram plants when exposed simultaneously to cadmium and lead, as well as the mutual effects of these two elements on marjoram behavior. Materials and Methods A factorial randomized complete block design experiment with four replications was used to study the effect of Cd in four concentrations (0, 6, 12 and 24 mg.kg-1 soil) as well as Pb in four concentrations (0, 150 300 and 450 mg. Kg-1 soil). The concentrations were determined based on previous reports and a preliminary experiment. Soil was prepared with appropriate amounts of cadmium chloride and lead chloride were added according to the desired concentrations. The contaminated soil was then incubated at field capacity moisture for two months. Seeds have been sown in germination trays. Seedlings at the three to four leaf stage were transferred to pots containing the contaminated soil. Plant harvest took place 42 to 52 days after the transfer to pots, specifically when the plants had just entered the flowering stage. The aboveground parts of the plants were harvested separately, and the roots were carefully removed from the soil. Half of the plants were dried at 105 °C for 24 h to determine the dry weight, Pb and Cd concentrations. The other half of the plants were used to measure biochemical traits including flavonoids, anthocyanins, malondialdehyde, protein, proline and some enzymatic antioxidants. The data was analyzed using a two-way analysis of variance (ANOVA), and the means were compared using the LSD test. A significance level of 95% was applied using SAS 9.2. Results and DiscussionIn this study, various parameters were measured including the dry weight of aerial parts and roots, concentrations of lead and cadmium in the aerial parts and roots, lipid peroxidation (MDA), flavonoids, anthocyanins, total phenols, proline, protein, and antioxidant enzymes including guaiacol peroxidase (GPX), ascorbate peroxidase (APX), and catalase (CAT). The results of the analysis of variance showed that all the mentioned traits were influenced by the individual effects of lead and cadmium. However, there was no significant interaction between cadmium and lead on proline, protein, GPX, polyphenols, flavonoids, and anthocyanins. The dry weight of aerial parts and roots decreased in the presence of cadmium and lead, while the concentrations of lead and cadmium increased. However, this damage was more pronounced in the presence of cadmium compared to lead. The presence of cadmium in a lead-containing environment had an inhibitory effect on lead uptake by the plant, and vice versa. The highest level of MDA was reported in the combination of lead and cadmium concentrations of 450 and 24 mg/kg, respectively. The analysis of enzyme activity showed that the maximum catalase activity was observed in the combination of 6 and 450 mg/kg of cadmium and lead, respectively, while the minimum activity was found in the control group. Similarly, the highest APX activity was reported in the combination of 24 mg/kg of cadmium and zero lead, while the lowest activity was observed in the control group. The use of cadmium and lead at the highest consumption level compared to the control group resulted in a 204% and 40% increase in GPX activity, respectively. In the analysis of total phenols, flavonoids, anthocyanins, and protein, an increase in cadmium concentration from zero to 24 mg/kg led to a decrease of 52%, 42%, 208%, and 81%, respectively, while protein decreased by 39%. These traits showed an increase of 14%, 14%, 58%, and 40%, respectively, with an increase in lead concentration from zero to 450 mg/kg, while protein decreased by 24%. Based on the results, it appears that the increase in secondary metabolites with the increase in heavy metals has accompanied the plant's response to the prevailing conditions. Conclusion The study found that both cadmium and lead negatively affect the dry weight of plants, with cadmium having a greater impact. This reduction is particularly noticeable in photosynthesis, pigments, electron transport chain, and energy production. The highest concentrations of lead and cadmium (24-450 mg/kg) show the maximum decrease. As the concentrations of these elements increase in the growth medium, their concentration in the plants also increases. Lead has lower mobility and tends to accumulate in the roots compared to cadmium. Interestingly, the presence of cadmium inhibits the uptake of lead by the plant, and vice versa. This leads to an average inhibition of 39% for lead uptake by cadmium and 35% for cadmium uptake by lead in the aerial parts. The study also observed an increase in secondary metabolites, which act as antioxidants and help the plant cope with the stresses caused by cadmium and lead. These metabolites may also contribute to osmotic regulation along with the increase in proline. Based on these findings, it seems that these plants can be used in green spaces contaminated with moderate to low levels of cadmium and lead, particularly in mining areas.