Lead‐induced excessive lipid peroxidation and changes in local cerebral blood flow in rabbit brain

Abstract

Lead‐poisoning is a disease of environmental origin. The primary target for lead is the nervous system. Lead ions are able to accelerate lipid peroxidation (LP) and, hence, induce cellular damage. Endothelial cell alteration and cerebral microvessel dysfunction are important in lead‐induced encephalopathy. It is possibile that the altered functional state of brain microvasculature cannot ensure the adequate level of local cerebral blood flow (LCBF). The purpose of the present study was to evaluate LP in brain tissue homogenates of the cerebral cortex (CTX) and hypothalamus (HYP) of 15 lead‐exposed vs seven control rabbits after a short‐time lead exposure (5 and 10 days, 40 mg/kg). Another aim was to compare the dynamics of changes in LP and LCBF, detected by the H2 clearance method in another group (seven lead‐exposed rabbits vs seven controls). The basal level of thiobarbituric acid reactive substances (TBARS), the Fe‐stimulated part of the TBARS (Fe‐TBARS) and diene conjugates (DC) were used for the evaluation of LP in the brain tissue. A tendency to the slight enhancement of TBARS and DC concentrations in brain homogenates 5 days after the 10 days lead exposure period was found (CTX p < 0.05). The enhancement of the Fe TBARS was expressed maximally on 1 day after 10 day exposure period (CTX p < 0.05, HYP p < 0.001 compared to controls). The biphasic reaction of changes in LCBF was detected: during (5th day) and in 1 day after a 10 day exposure period a decrease of LCBF in both investigated regions was found (10.5 and 9.3 ml/100g/min i.e. 28.6 and 24.1%, respectively, in CTX, p < 0.05; and 11.2 and 10.1 ml/100g/min i.e. 19.9 and 18.7%, respectively in HYP, p < 0.05); on the 5th day after exposure minimal tendency to increase was found (7.1 ml/100g/min, p < 0.01 in HYP compared with controls). In conclusion, lead induces excessive LP in brain homogenates and disturbances in LCBF. However, the causal relationship between those events remains to be proven.