Oxidative Effects of Lead in Young and Adult Fisher 344 Rats
2003, Archives of Environmental Contamination and Toxicology
https://doi.org/10.1007/S00244-002-2023-4Abstract
Lead poisoning has been extensively studied over the years. Many adverse physiological and behavioral impacts on the human body have been reported due to the entry of this heavy metal. It especially causes the hematological effects to people of all ages. However, its molecular mechanisms of action remain largely unknown. Hence, the aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by lead nitrate in a human leukemia cell line using the MTT [3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide], and lipid hydroperoxide assays, respectively. HL-60 cells were treated with different doses of lead nitrate for 24 h prior to cytotoxicity oxidative stress assessment. The results obtained from the MTT assay indicated that lead nitrate significantly decreases the viability of HL-60 cells in a dose-dependent manner. Similar result was obtained with the trypan blue exclusion test. Data generated from lipid hydroperoxide assay resulted in a significant increase (p < 0.05) in the production of hydroperoxides (degradation products of lipid peroxidation) with increasing doses of lead nitrate. Upon 24 h of exposure, the hydroperoxide concentrations in the sample [μM] (mean ±SE, n = 3) compared to untreated control were 6.7 ± 2, 7.1 ± 1, 14.7 ± 2, 15.7 ± 1, 16.2 ± 1, and 15.2 ± 1 in 0, 10, 20, 30, 40, and 50. μg/mL of lead nitrate, respectively. In summary, findings from this study demonstrated that lead nitrate is cytotoxic to HL-60 cells. This cytotoxicity is found to be associated with oxidative stress. Although there are many studies showing evidence that lead is a multi-targeted toxicant, causing effects in the gastrointestinal tract, cardiovascular system, central and peripheral nervous systems, immune system, and reproductive system, little is known about the effect of lead on the hematopoietic system. Hence, the present study was designed to use human leukemia (HL-60) cells as models to determine whether exposure to lead is associated with the
References (16)
- Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Lead. Public Health Service, U.S. Department of Health and Human Services; Atlanta, GA: 1999.
- Hermes-Lima M, Valle VGR, Vercesi AE, Bechara EJH. Damage to rat liver mitochondria promoted by δ-aminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphria and lead poisoning. Biochim Biophys Acta 1991;1056:57-63. [PubMed: 1984785]
- Tchounwou PB, Yedjou CG, Foxx D, Ishaque A, Shen E. Lead induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells. Mol Cell Biochem 2004;255:161-170. [PubMed: 14971657]
- Tully DB, Collins BJ, Overstreet JD, Smith CS, Dinse GE, Mumtaz MM, Chapin RE. Effects of arsenic, cadmium, chromium and lead on gene expression regulated by a battery of 13 different promoters in recombinant HepG 2 cells. Toxicol Appl Pharmacol 2000;168:79-90. [PubMed: 11032763]
- Tchounwou PB, Yedjou CG, Dorsey WC. arsenic trioxide induced transcriptional activation and expression of stress genes in human liver carcinoma cells (HepG2). Cellular and Molecular Biology 2003;49(7):1071-1079. [PubMed: 14682389]
- Sengupta M, Bishayi B. Effect of lead and arsenic on murine macrophage response. Drug Chem Toxicol 2002;25:459-472. [PubMed: 12378952]
- Centers for Disease control (CDC). Fatal pediatric lead poisoning, New Hampshire, 2000. Morb Mort Weekly Rep 2001;50(22):457-459.
- Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymo 1990;186:1-85.
- Lin F, Girotti AW. Photodynamic action of merocyanine 540 on leukemia cells: iron-stimulated lipid peroxidation and cell killing. Arch Biochem Biophys 1993;300:714-723. [PubMed: 8434951]
- Suzuki YJ, Forman HF, Sevanian A. Oxidants as stimulators of signal transduction. J Free Rad Biol Med 1997;22:269-285.
- Esterbaur H, Schaur RJ, Zoller H. Chemistry and Biochemistry of 4-Hydroxynonenal, Malonaldehyde and related Aldehydes. Free Rad Biol Med 1991;11:81-128. [PubMed: 1937131]
- Mazhoudi S, Chaoui A, Ghorbal MH, El Ferjani E. Response of antioxidative enzymes to excess copper in tomato (Lycopersicm esculentum, Mill). Plant Sci 1997;127:129-137.
- Ding Y, Vaziri ND, Gonick HC. Lead-induced hypertension, II: response to sequential infusions of L-arginine, superoxide dismutase, and nitroprusside. Environ Res 1998;76:107-113. [PubMed: 9515065]
- Prasad KVSK, Paradha Saradhi P, Sharmila P. Concerted action of antioxidant enzymes and curtailed growth under zinc toxicity in Brassica juncea. Environ Exp Botany 1999;42:1-10.
- Clijsters A, Cuypers A, Vangronsveld J. Physiological responses to heavy metals in higher plants. Defence against oxidative stress. Z Naturforsch 1999;54c:730-734.
- Stroinski A, Kozlowska M. Cadmium-induced oxidative stress in potato tuber. Acta Soc Bot Po 1997;66:189-195.