Effect of Heavy Metals on Non-muscle Invasive Bladder Cancer and Its Relation to TLR Signaling Pathway

Heavy metals are widely acknowledged as environmental hazards because of its toxicity, and bioaccumulation in all living organisms. The air, water, and soil are polluted by most heavy metals, which can be fatal to humans. Heavy metals can enter humans through the food chain if they oxidize or combine with other environmental elements (such as water, soil, or air). Hence, We attempt to evaluate five heavy metals are Iron (Fe), Copper, lead, Cadmium (Cd), and Zink levels in NMIBC patients and their relationship with the expression of TLRs gene pathway. The study comprised a cohort of 100 patients diagnosed with NMIBC and an equivalent number of 100 persons who were in good health. Blood samples were collected from patients group and control group. Inductively coupled plasma optical emission spectrometry was employed to measure the levels of Pb, Zn, Fe, Cd, and Cu in the blood samples. Moreover, the gene expression of TLR4, TLR2, MYD88 and NFKB1 were investigated in blood samples. The presence of heavy metals in the blood was shown to be correlated with the observed gene expression outcomes. A comparison between two groups revealed a considerable rise in metal levels of Cd, Fe, Cu, Pb, and Zn in NMIBC compared to the control group. There is a notable rise in the levels of TLR2, TLR4, Myd88, and NFKB in NMIBC compared to the control group. Upon analysing the correlation coefficients between m-RNA gene expression and the level of heavy metals, we discovered a positive correlation between cadmium and the gene expressions for (TLR2, TLR4, Myd88, and NFKB). However, we did not find any correlation between other metals Fe, Cu, Pb, and Zn, and the gene expression. It found that selected heavy metals in our study were a significant with NMIBC group more than the control group. And also a selected gene expression was significant with NMIBC group more than the control group. Cadmium shows a correlation in NMIBC with TLR2, TLR4, Myd88 and NFKB. An increase in blood level of Cd, Fe, Zn, Pb, and Cu and the disturbance of each of TLR2, TLR4, Myd88, and NFKB may have an impact on the pathogenesis of NMIBC. The increase in Cd level in has an important role in pathogenesis of NMIBC through the TLRs genes (TLR2, TLR4, Myd88 and NFKB).