Lead is a ubiquitous
element in the environment causing oxidative burst in the exposed individuals leading to tissue damage.
Antioxidants have long been known to reduce the
free radical-mediated oxidative stress while,
thiol chelators have been used to treat
arsenic toxicity. The therapeutic efficacy of
melatonin or
N-acetylcysteine (NAC) was studied in the present study, both individually and in combination with a potent
thiol-
chelating agent, meso
2,3-dimercaptosuccinic acid (
DMSA), in reducing lead concentration in blood and other soft tissues. Their ability to restore altered haematopoietic, hepatic and other biochemical variables indicative of tissue oxidative stress in male rats was also investigated. Administration of
melatonin and NAC individually, provided significant protection to lead induced disturbed
antioxidant defense that may significantly compromise normal cellular function. Administration of
melatonin and NAC also provided a significant protection to
thiobarbituric acid reactive substances (
TBARS) levels,
reduced glutathione (GSH) and
oxidized glutathione (
GSSG) contents in tissues, suggesting their ability to act as a
free radical scavenger and in protecting cells against toxic insult. NAC, a
thiol containing
antioxidant, has been used under several clinical conditions with few adverse side effects. It has a high toxicity threshold and its wide therapeutic window enhances its utility. The
antioxidant action of NAC is due to its ability to interact with
reactive oxygen species (ROS) or its ability to stimulate endogenous
glutathione (GSH) synthesis.
DMSA, on the other hand when given alone, provided significant recovery in restoring the altered lead sensitive biochemical indices like blood
delta-aminolevulinic acid dehydratase (ALAD), urinary
delta-aminolevulinic acid (ALA), beside increasing urinary lead excretion and decreasing lead concentration in blood and soft tissues. Interestingly, combined treatment of
DMSA and NAC provided more pronounced efficacy in restoring altered biochemical variables and in reducing body lead burden than monotherapy with
DMSA. The results thus, suggest the involvement of ROS in lead toxicity and a pronounced beneficial role of NAC in therapeutic implications of
lead poisoning when co-administered with a
thiol chelator (
DMSA) supporting the hypothesis that cellular redox status may be significantly reversed by utilizing a
thiol containing
antioxidant compound. It can be concluded that, combined
therapy with an
antioxidant moiety and a
thiol-
chelating agent may be a better choice for treating plumbism.