Antioxidant effects of α tocopherol, ascorbic acid and l-methionine on lead induced oxidative stress to the liver, kidney and brain in rats
Introduction
Lead is a common environmental and industrial pollutant that has been detected in all phases of environment and biological system. The persistence of lead in the animals and humans and the associated health risk is a topic of current debate and concern (Juberg et al., 1997). Lead has been found to produce wide range of toxic-biochemical effects, besides behavioral dysfunction in man and in experimental animals (Klassen, 1990).
Liver, kidneys and brain have been considered as the target organs for the toxic effects of lead (Sharma and Street, 1980). Chronic exposure to this biotoxicant leads to its accumulation in these organs with maximum concentration per gram weight of tissue being recorded in kidneys (Humphreys, 1991). The neurotoxic effect of lead, particularly in the developing brain is a matter of serious concern and behavioral abnormalities, learning impairment, decreased hearing and impaired cognitive functions in humans and experimental animals have been recorded with blood lead levels as low as 10 μg/dl (Bressler et al., 1999).
Although several mechanisms have been proposed to explain the lead-induced toxicity (Tian and Lowrence, 1995), no mechanisms have been yet defined explicitly. Recent studies suggest oxidative stress as one of the important mechanisms of toxic effects of lead (Ercal et al., 1996, Gurer et al., 1998). The oxidative stress has also been implicated to contribute to lead-associated tissue injury in the liver, kidneys, brain and other organs (Halliwell, 1994a, Adonaylo and Oteiza, 1999). Indirect in vivo evidence of oxidative involvement in lead-induced pathotoxicity was demonstrated by alleviation of oxidative stress in the erythrocytes after treatment with thiol containing proven antioxidants, N-acetyl cystein, and a succimer in lead exposed rats (Gurer et al., 1998). Also, reactive oxygen species related lead toxicity in the rat sperm was prevented by supplementation of rat feed with vitamin E and or vitamin C (Hsu et al., 1998). These recent findings suggest potential role of antioxidants to ameliorate lead toxicity.
Vitamin E (α tocopherol) and ascorbic acid (vitamin C) are low molecular mass antioxidants that interact directly with the oxidizing radicals (Burton and Ingold, 1986, Jones et al., 1995) and protect the cells from reactive oxygen species (Halliwell, 1994b). The lipid soluble, non-enzymatic antioxidant, α tocopherol checks the lipid peroxidation through limiting the propagation of chain reaction of lipid peroxidation (Buetter, 1993) where as vitamin C scavenges the aqueous reactive oxygen species (ROS) by very rapid electron transfer that, thus, inhibits lipid peroxidation (Halliwell et al., 1987).
Methionine is readily taken up by the hepatocytes than cystein for the direct synthesis of glutathione (Reed and Orrenius, 1997) and, thus, acts as a precursor amino acid for this low molecular weight antioxidant (Meister, 1981). Glutathione protects the cells from oxidative damage and plays vital role in detoxification (Reed, 1990). In addition, the thiol group of methionine may chelate lead from tissues. The present investigation was conducted to determine whether the treatment of lead-exposed rats with α tocopherol, ascorbic acid or l-methionine protects the target and vital organs, viz. liver, kidneys and brain from lead associated oxidative stress.
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Animals and experimental design
The experiment was performed with IVRI 2CQ rats weighing about 100 g. The animals were housed in plastic cages and provided with ad lib standard laboratory animal feed, and water. They were randomly assigned into six groups. Group I (n=6) served as control and received daily ip injection of sterile normal saline solution for 4 weeks. Group II (lead group) served as positive control and received daily 1 mg Pb2+/kg b.w ip as lead acetate solution for 4 weeks. During 5th week no treatment was
Lead concentration in blood and tissues
Table 1 shows blood lead concentration and lead burden in the liver, kidney and brain. Animals given lead for 4 weeks and allowed 1 week to recover had blood lead levels of approximately 70 μg/dl, which was reduced to 46 μg/dl with methionine treatment. The blood lead levels in all the treatment groups remained significantly higher than the control and, were comparable to lead group in spite of treatment with the known conventional chelator, CaNa2 EDTA for a period of 4 days. The maximum
Discussion
Lead is a pervasive environmental pollutant with no beneficial biological role. The higher concentration of lead in different tissues and RBCs following occupational or experimental exposure was associated with increased oxidative reaction, which might be responsible, at least in part, for lead-induced toxic effects (Monteiro et al., 1985, Gurer et al., 1998, Patra and Swarup, 2000). In the present study, rats were subjected to subchronic exposure to lead for a period of 4 weeks followed by
Conclusion
It is concluded from this experiment that lead exposure led to varying degree of increased lipid peroxidation with tissue specific changes in liver, kidneys and brain. Treatment of lead-exposed rats with α tocopherol and ascorbic acid did not reduce tissue lead burden but lowered the LPO levels revealing their antioxidant potential in lead-related oxidative stress.
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