Lead and ethanol co-exposure lead to blood oxidative stress and subsequent neuronal apoptosis in rats.
OBJECTIVE
The present study was aimed at investigating chronic exposure to lead and ethanol, individually and in combination with blood oxidative stress leading to possible brain apoptosis in rats.


METHODS
Rats were exposed to lead (0.1% w/v in drinking water) or ethanol (1 and 10%) either individually or in combination for four months. Biochemical variables indicative of oxidative stress (blood and brain) and brain apoptosis were examined. Native polyacrylamide agarose gel electrophoresis was carried out in brain homogenates for glucose-6-phosphate dehydrogenase (G6PD) analysis, whereas western blot analysis was done for the determination of apoptotic markers like Bax, Bcl-2, caspase-3, cytochrome c and p53.


RESULTS
The results suggest that most pronounced increase in oxidative stress in red blood cells and brain of animals co-exposed to lead and 10% ethanol compared all the other groups. Decrease in G6PD activity followed the same trend. Upregulation of Bax, cytochrome c, caspase-3, p53 and down-regulation of Bcl-2 suggested apoptosis in the rat brain co-exposed to lead and ethanol (10%) compared with their individual exposures. Significantly high lead accumulation in blood and brain during co-exposure further support synergistic toxicity.


CONCLUSIONS
The present study thus suggests that higher consumption of ethanol during lead exposure may lead to brain apoptosis, which may be mediated through oxidative stress.
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India. sjsflora@hotmail.com
Swaran J S
SJ
Flora
Pratibha
P
Gautam
Pramod
P
Kushwaha
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D054316:Biomarkers, Pharmacological / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D054316:Biomarkers, Pharmacological; D009942:Organometallic Compounds; D000431:Ethanol; D005954:Glucosephosphate Dehydrogenase; C008261:lead acetate