Evaluation Of Oxidative Damage Induced By Lead In Mice Using Multi-biomarkers

Lead is a common heavy metal element in the environment. Because of its malleability, low melting point, ability to form compounds and resistance to corrosion, it is broadly used in daily lives and industrial manufactures. In these applications, however, only one quarter of lead is reclaimed, and the rest is mostly emitted to the environmental medium. As an unbiodegradable material, lead exists in form of minim and trace persistently, and continuously enters into human bodies via the food, soil, water and air, causing threat to human health.A variety of researches show lead is toxic to almost all organs and organ systems, especially the central and peripheral nervous systems, the hematological system, the cardiovascular system, the livers, the kidneys, and the male and female reproductive systems. Lead was even defined as the first killer to children's health in America. However, the exact mechanisms of lead have not been extensively understood. Along with the progress on the free radical research, recent studies have reported that inducing oxidative stress in cells may be one of the primary mechanisms of lead toxicity. Therefore, the biological markers of oxidant and antioxidant systems used as toxicological indicators of lead exposure are widely investigated.In the present study, multiple oxidative stress parameters were used to determine the inductions of oxidative damage and the effects on antioxidant defense system in target tissues (liver, kidney, and peripheral blood) by subacute lead exposure. Furthermore the relationships between these indices as well as the inner changeable mechanisms were also analyzed. The principal aim of this study therefore is to further discuss the lead toxic mechanisms and the probabilities of the above indices served as biomarkers of lead exposure.Twenty-five male 1CR mice were divided into five groups randomly, different dosages of lead acetate (0, 10, 50, 100, 500 mg/kg body weight respectively) were administered by oral gavage every other day for four weeks. The comet assay was used to measure the DNA damage in peripheral blood lymphocytes. The levels of mitochondrial ROS formation, the contents of MDA, the activities of SOD, CAT, GSH-Px, GR and GST in liver and kidney were also determined.Main results:1. The liver mitochondrial ROS formations increased in response to dosages of lead acetate, and its level in 500 mg/kg BW lead-treated group was substantially higher when compared with the control group. However, kidney mitochondrial ROS level in 100 mg/kg BW lead-treated group decreased significantly.2. The contents of liver MDA increased evidently in 50, 100 and 500 mg/kg BW lead-treated groups, and the differences were proved to be statistically significant. Kidney MDA contents in 10, 50 and 500 mg/kg BW groups also raised significantly.3. The activities of liver SOD increased clearly in all lead-treated groups, and the differences were proved to be statistically significant. While kidney SOD activities in 10, 50 and 500 mg/kg BW groups were inhibited significantly.4. No significant alterations of liver CAT activities were observed. While kidneyCAT activities in all lead-treated groups were inhibited significantly.5. No significant variations of GSH-Px activities were observed both in liver and kidney.6. The liver GR activities increased in response to dosages of lead acetate, and its activities in 50,100 and 500 mg/kg BW lead-treated groups were substantially higher when compared with the control group. Kidney GR activities in 100 and 500 mg/kg BW groups also increased significantly.7. The liver GST activities increased in response to dosages of lead acetate, and its activities in 100 and 500 mg/kg BW lead-treated groups were substantially higher when compared with the control group. Kidney GST activity in 500 mg/kg BW group also increased significantly.8. Both the tail lengths and tail moments in 50, 100 and 500 mg/kg BW lead-treated groups in peripheral blood lymphocytes increased significantly, meanwhile there was;an excellent correlation between the tail lengths and tail moments.Main conclusions:1. The present research showed that subacute lead exposure could disrupt the mitochondrial ROS metabolism, causing the mitochondrial ROS formation increase or decrease. Compared with kidney, the metabolism of mitochondrial ROS in liver was more active.2. MDA is a well-known biomarker of oxidative damage. Its contents were found to increase obviously both in liver and kidney at low dosages, suggesting lipid peroxidation was a significant manifestation of lead toxic damage.3. DNA strand breaks induced by oxidative stress may also serve as a usefulbiological indicator of oxidative damage. A severe DNA rupture was observed in the present study. Judging from the similar alteration trends of MDA contents and tail lengths/tail moments, it was considered that the lipid peroxidation might play a dominant role in the process of DNA fragments.4. SOD, CAT and GSH redox system enzymes are mutual coupled biomarkers used to estimate antioxidant defense ability of the body. The present study found the above antioxidant enzyme activities took on some changes both in liver and kidney, indicating lead exposure could affect the antioxidant defense systems;different enzymes had different change patterns against oxidative stress.