Impact of Heavy Metals and Oxidative Stress on Kidney Function and Male Reproductive Hormones in Different Areas in Erbil Province

Abstract

Industrial pollution constitutes a significant public health threat, mainly due to prolonged exposure to hazardous heavy metals (HMs). This extensive study measured systemic exposure and related biological effects by evaluating serum levels of cadmium (Cd), chromium (Cr), nickel (Ni), tin (Sn), zinc (Zn), and boron (B), in conjunction with critical biomarkers of oxidative stress (OS), renal function, and male reproductive hormones. This study comprised of 135 adult male volunteers categorized into three separate groups: rural dwellers (n = 44, reference group, Harir District), urban residents (n = 48, Erbil City Center), and industrial workers (n = 43, Erbil, Gwer-Road) in Erbil Province, Kurdistan Region, Iraq. Advanced analytical methods were utilized: Inductively Coupled Plasma Mass-Spectrometry (ICP-MS) for HMs, Enzyme-Linked Immunosorbent Assay (ELISA) for OS markers, 8-Hydroxy-2′-deoxyguanosine (8-OHdG), Nitric Oxide (NO), Catalase (CAT), Glutathione Peroxidase (GPx), and automated immunoassays (KENZA 240 TX/ISE) for renal biomarkers (urea, creatinine, uric acid) and (Cobas e411) for male reproductive hormones, Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Testosterone.
The findings demonstrated significant exposure gradients. Industrial workers showed that markedly increased HMs concentrations, particularly for the strong nephrotoxin cadmium (Cd: 0.203 µg/L, 95% CI: 0.136-0.288 vs. rural: 0.102 µg/L, 95% CI: 0.085-0.102; Cohen’s d = 1.2445, P = 0.007), suggesting significant occupational exposure. In contrast, urban inhabitants exhibited a notable deficit in the vital trace element zinc (Zn: 2162 µg/L compared to rural: 3991 µg/L; d = 1.029, P = 0.0029), indicating possible dietary insufficiencies or heightened utilization/excretion associated with urban environmental stresses. Biomarkers revealed significant physiological disturbance. The OS markers like 8-OHdG which is the deoxyribonucleic acid (DNA) damage marker exhibited no significant variation among the study groups (P > 0.05), while NO levels were significantly decreased in urban and industrial areas compared to the rural area (P ˂ 0.05). The antioxidant defense capability was markedly impaired in the exposed groups, as indicated by significantly reduced levels of essential antioxidant activities CAT, and GPx in both urban and industrial participants (P < 0.0001); however, the renal impairment was apparent, with individuals in urban/industrial regions demonstrating significant increases in urea (26-27%) and creatinine (16-19%) relative to rural controls, indicating declining kidney function. Moreover, industrial workers exhibited considerable endocrine disturbance, evidenced by significantly elevated levels of FSH (38.9% rise), LH (42.9% increase), and testosterone (24.9% increase) relative to the rural inhabitants.
Significant exposure-response associations were established. Zn exhibited moderate positive correlations with antioxidant enzymes (GPx: r = 0.6199, P < 0.0001 and CAT: r = 0.4800, P < 0.0001), emphasizing its essential protective function. Cd exhibited notable positive associations with creatinine (r = 0.3586, P = 0.0015) and testosterone (r = 0.3050, P = 0.0063), while it was demonstrating a negative correlation with CAT (r = -0.3344, P = 0.005). These findings indicate that industrial HMs exposure, especially Cd, causes systemic toxicity. The molecular process entails the development of OS (suppression of CAT/GPx), which subsequently leads to renal failure (increased urea/creatinine associated with Cd) and endocrine disturbance (elevated FSH, LH, and testosterone correlated with Cd). The significant increase in gonadotropins (FSH, LH) and testosterone in exposed workers necessitates further examination of possible early testicular dysfunction or compensatory responses. The notable exposure-response correlations indicate that it is urgent to implement demanding environmental monitoring, strict occupational health, and safety measures (including improved personal protective equipment and workplace sanitation), and focused on public health initiatives in high-risk industrial regions such as Erbil to mitigate these substantial health hazards.