title: Accumulation of methylglyoxal and d-lactate in Pb-induced nephrotoxicity in rats.
abstract: Lead (Pb) is an environmental pollutant associated with several diseases, such as nephrotoxicity. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis and reported to increase in kidney damage. Metformin is used as an MG scavenger in the clinic. In this study, we investigated the mechanism of Pb-induced renal injury and the effect of metformin on Pb-induced nephrotoxicity. Eighteen Wistar rats were randomly divided into three groups: control, Pb, and Pb + metformin groups. Pb (250 ppm) was administered in drinking water, and 50 mg/kg of metformin was co-administered orally. After 28 days, the levels of MG and its metabolite d-lactate in urine, serum and renal tissues were examined. The elevation of renal MG (56.86 ± 17.47 vs 36.40 ± 5.69, p < 0.01) and urinary d-lactate (0.68 ± 0.28 vs 0.32 ± 0.13, p < 0.01) was observed in Pb-exposed rats compared with those in control rats. After co-treatment with metformin, these phenomena were attenuated. In the present study, it was demonstrated for the first time that urinary d-lactate might serve as the candidate marker for Pb-induced nephrotoxicity in the clinic, and metformin might be a new therapeutic candidate for Pb poisoning.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Shen
authors.initials: YS
authors.lastname: Huang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Li
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Pei-Yun
authors.initials: PY
authors.lastname: Tsai
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-En
authors.initials: CE
authors.lastname: Lin
authors.affiliation: Department of Electro-Optical Engineering, National Taipei University of Technology, Taipei, Taiwan.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jen-Ai
authors.initials: JA
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D007773:Lactates / Q000032:analysis / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000032:analysis / Q000378:metabolism*; D017208:Rats, Wistar; D014527:Uric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D007773:Lactates; D014527:Uric Acid; D007854:Lead; D011765:Pyruvaldehyde; D008687:Metformin; D003404:Creatinine; D007770:L-Lactate Dehydrogenase
keywords: Pb; d-lactate; heavy metal; methylglyoxal; nephrotoxicity