Effects of lead on glutathione S-transferase expression in rat kidney: a dose-response study
- PMID: 10048128
- DOI: 10.1006/toxs.1998.2543
Effects of lead on glutathione S-transferase expression in rat kidney: a dose-response study
Abstract
Glutathione S-transferases (GST, EC 2.5.1.18) are a family of phase II detoxification enzymes involved in the conjugation of glutathione to a highly diverse group of compounds. The purpose of this study was to evaluate the dose-response effects of lead acetate administration on the expression of rat kidney GST. Sprague-Dawley rats were injected with doses of lead acetate ranging from 0.11 to 114 mg/kg (0.3 to 300 mumol/kg) for three consecutive days and sacrificed 24 h later. Kidney GST activity, GST isoform HPLC profiles, blood lead analysis, and electron microscopy were performed. A dose of 1.1 mg/kg lead acetate resulted in a blood lead level of 26 micrograms/dl and produced a significant increase in GST activity which continued to increase with dose up to 38 mg/kg. Morphological changes were detected at 3.8 mg/kg and increasing severity of cellular damage paralleled dose, blood lead levels, and changes in body weight. Individual GST isoforms exhibited different thresholds and maxima; rGSTP1 and rGSTM1 had thresholds of 1.1 and 3.8 mg/kg, respectively, very similar rates of increase with dose, and a maximum yield that was 450% above control at a dose of 38 mg/kg for both enzymes. rGSTA1 and rGSTA3 showed similar thresholds (1.1 mg/kg) and maximal fold increase (275%) but varied in the relative response to each dose. These results indicate that renal GST increases occur at lead levels which are environmentally significant, that these changes precede cellular damage, and suggest that GST may serve as a tissue biomarker of lead exposure.
Similar articles
-
Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes.Toxicol Appl Pharmacol. 1995 Mar;131(1):85-93. doi: 10.1006/taap.1995.1050. Toxicol Appl Pharmacol. 1995. PMID: 7878682
-
Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies.Toxicol Appl Pharmacol. 1995 Mar;131(1):94-107. doi: 10.1006/taap.1995.1051. Toxicol Appl Pharmacol. 1995. PMID: 7878683
-
Glutathione S-transferases: two-dimensional electrophoretic protein markers of lead exposure.Electrophoresis. 1998 Jun;19(8-9):1332-5. doi: 10.1002/elps.1150190821. Electrophoresis. 1998. PMID: 9694276
-
Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max).Fundam Clin Pharmacol. 2006 Jun;20(3):263-71. doi: 10.1111/j.1472-8206.2006.00407.x. Fundam Clin Pharmacol. 2006. PMID: 16671961
-
Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function.J Clin Anesth. 2015 Feb;27(1):73-9. doi: 10.1016/j.jclinane.2014.07.002. Epub 2014 Nov 20. J Clin Anesth. 2015. PMID: 25468579 Review.
Cited by
-
Interactions of Betel Quid Constituents with Drug Disposition Pathways: An Overview.Curr Drug Metab. 2023;24(2):92-105. doi: 10.2174/1389200224666230228142052. Curr Drug Metab. 2023. PMID: 36852799 Free PMC article.
-
Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors.Int J Environ Res Public Health. 2021 Aug 15;18(16):8625. doi: 10.3390/ijerph18168625. Int J Environ Res Public Health. 2021. PMID: 34444373 Free PMC article.
-
Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study.Front Genet. 2021 Jun 16;12:664946. doi: 10.3389/fgene.2021.664946. eCollection 2021. Front Genet. 2021. PMID: 34220941 Free PMC article.
-
Prevention of gastrointestinal lead poisoning using recombinant Lactococcus lactis expressing human metallothionein-I fusion protein.Sci Rep. 2016 Apr 5;6:23716. doi: 10.1038/srep23716. Sci Rep. 2016. PMID: 27045906 Free PMC article.
-
Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio.Fish Physiol Biochem. 2014 Apr;40(2):355-63. doi: 10.1007/s10695-013-9848-9. Epub 2013 Aug 24. Fish Physiol Biochem. 2014. PMID: 23974671
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials