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. 2023 Mar 9;11(3):256.
doi: 10.3390/toxics11030256.

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Dragana Vukelić  1 , Aleksandra Buha Djordjevic  1 , Milena Anđelković  1   2 , Evica Antonijević Miljaković  1 , Katarina Baralić  1 , Katarina Živančević  1   3 , Petar Bulat  4   5 , Jelena Radovanović  6 , Danijela Đukić-Ćosić  1 , Biljana Antonijević  1 , Zorica Bulat  1
Affiliations

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Dragana Vukelić et al. Toxics. .

Abstract

Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simulate low-dose Pb exposure in an animal model with the aim of assessing oxidative status and essential element levels as the main mechanism of Pb toxicity in the liver and kidneys. Furthermore, dose-response modelling was performed in order to determine the benchmark dose (BMD). Forty-two male Wistar rats were divided into seven groups: one control group, and six groups treated for 28 days with 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg b.w./day, respectively. Oxidative status parameters (superoxide dismutase activity (SOD), superoxide anion radical (O2-), malondialdehyde (MDA), total sulfhydryl groups (SHG), and advanced oxidation protein products (AOPP)) and Pb, copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels were measured. Lowering Cu levels (BMD: 2.7 ng/kg b.w./day), raising AOPP levels (BMD: 0.25 µg/kg b.w./day) in the liver, and inhibiting SOD (BMD: 1.3 ng/kg b.w./day) in the kidneys appear to be the main mechanisms of Pb toxicity. The lowest BMD was derived for a decrease in Cu levels in liver, indicating that this effect is the most sensitive.

Keywords: Pb exposure; benchmark modelling; dose–response; essential elements; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Liver (a) and kidney (b) Pb levels in Wistar rats subacutely exposed to low levels of Pb over a period of 28 days. Results are presented as means ± SD. * † ‡ § # ∧ p < 0.05; §§ p < 0.01; *** ††† ‡‡‡ §§§ p < 0.001 compared to control, 0.1, 0.5, 1, 3, and 7 group, respectively, using ANOVA followed by Fisher’s LSD test.
Figure 2
Figure 2
Benchmark dose modeling of liver Cu (a) and AOPP (b) levels, and kidneys’ SOD (c) activity as a response to the external Pb dose (mg/kg b.w./day), using a model averaging method with 200 iterations, PROASTweb70.1 software (https://proastweb.rivm.nl/). The red triangles represent the medians.
Figure 3
Figure 3
Benchmark dose modeling of liver Cu levels as a response to the internal Pb dose–BLL (µg/dL) using a model averaging method with 200 iterations, PROASTweb70.1 software (https://proastweb.rivm.nl/). The red triangles represent the medians.
Figure 4
Figure 4
Benchmark dose modeling of the liver Cu levels as a response to the internal Pb dose–liver tissue level (µg/g) using a model averaging method with 200 iterations, PROASTweb70.1 software (https://proastweb.rivm.nl/). The red triangles represent the medians.
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