Effects of sub-chronic, low-dose cadmium exposure on kidney damage and potential mechanisms

Abstract

Background: The present study was to investigate the potential mechanisms underlying the sub-chronic low-dose cadmium (Cd) exposure induced renal injury in rats.Methods: Totally 40 male adult SD rats were randomly divided into four groups: control group, low-dose Cd group (1 mg/kg CdCl 2 ), moderate-dose Cd group (2.5 mg/kg) and high-dose Cd group (5 mg/kg).Results: From the 3 rd week, the body weight of rats in moderate-dose and high-dose declined significantly as compared to the control group (P<0.05); the liver to body weight ratio increased, the volumes of 24-hour urine and drinking-water decreased markedly (P<0.05), the BUN, SCr and β 2 -MG increased significantly, but the Fe 2+ concentration decreased markedly as compared to the control group (P<0.05); the serum MDA and SOD 1 content contents increased, but the serum SOD 2 and CAT contents decreased significantly in Cd-treated groups (P<0.05); Renal injury deteriorated with the increase in Cd dose; swelling glomeruli showed stenotic renal-tubules, and epithelial-cell-necrosis, shedding and accumulation in the lumen, massive infiltrated inflammatory cells and interstitial hyperaemia were observed; The mitochondria in renal-tubularepithelial-cells displayed swelling, deformation and vacuolation; the renal ROS content increased in Cdexposure-groups; the renal SOD 1 expression increased but the expression of SOD 2 and CAT decreased (P<0.05). The Bcl-2 expression decreased, but Bax expression and Bax/Bcl-2 ratio increased significantly in a Cd-dose dependent manner.Conclusions: Cd may cause renal injury in a dose dependent manner, which may be ascribed to the disordered Fe 2+ absorption, redox imbalance and apoptosis in the kidney.

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

“…Once inside the mitochondria, cadmium can bind thiol-containing proteins and impair the corresponding protein function [ 80 ]. Studies have demonstrated that upon exposure to cadmium, kidney mitochondria displayed deformation, swelling, and vaculation, concurrent with increased SOD1 expression and decreased SOD2 and catalase expression [ 115 ]. Additionally, the anti-apoptotic protein BCL-2 was also found decreased by cadmium exposure [ 115 ]; so was the ratio between reduced glutathione and oxidized glutathione [ 60 ].…”

Construction of Mode of Action for Cadmium-Induced Renal Tubular Dysfunction Based on a Toxicity Pathway-Oriented Approach

“…Moreover, another potential mechanism by which Cd may decrease the activity of antioxidant enzymes is an interaction with divalent elements, such as manganese, zinc, and selenium; these elements function as cofactors and form the core active sites of antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione reductase) (Cuypers et al, 2010;Matović et al, 2015). After chronic exposure to low-dose Cd, nephrotoxicity occurs with increased renal ROS level and decreased activity of antioxidant enzymes (Wang et al, 2013;Ansari et al, 2017;Liu et al, 2019). However, oxidative stress is a dynamic equilibrium process; there is an adaptive system to eliminate ROS, and oxidative damage would appear only when ROS was overloaded.…”

Cadmium Toxicity and some Target Organs: A Review

“…The epithelial cells in the glomeruli of the renal glomeruli and the absence of urinary space in the Bowman capsule enlarge due to the large capillary expansion (31). The glomeruli swell, the renal tubules narrow, the epithelial cells in the renal tubules die, accumulate in the cavities, infiltration of inflammatory cells and edema (18). Congestion and inflammation around the blood vessels, fibrosis of the tissue and condensed nuclei in the cells of the renal tubules (28).…”

“…However, the initial stages of cadmium-induced proximal tubule damage may include many specific changes in cellular signaling pathway, cellular adhesions, and autophagy that happen before the onset of necrotic or apoptotic mechanisms (49). Cadmium may cause renal damage according to the method of giving, which may be ascribed to the disordered absorption of iron ions, disruption of oxidative stress and apoptosis in the kidney (18).…”

“…The amount of cadmium can be estimated in blood, urine, saliva, hair and nails (17). It causes a decrease in body weight, an increase in the weight of the liver compared to body weight, less drinking water, and less urine (18). Cadmium has dangerous effects on the body's immunity and inhibits the humoral and cellular immune response in immune cells, and accumulates in the spleen (19).…”