Effects of combined administration of calcium, iron, zinc, chrysanthemum flavonoids, and DMSA on the treatment of lead intoxication in mice

J Biochem Mol Toxicol. 2020 Feb;34(2):e22425. doi: 10.1002/jbt.22425. Epub 2019 Nov 15.

Abstract

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 μL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L16 (215 ) orthogonal design. The remaining two groups were given treatment with low and high doses of DMSA, respectively. After three weeks of intervention (ig), the optimal treatment group was identified according to its blood lead level, as well as some antioxidant indices in the blood, liver, and hippocampus. The results indicated that the combined administration of Fe, Zn, chrysanthemum flavonoids, and DMSA with low dosage had the most significant effect on increasing the activities of blood delta-aminolevulinic acid dehydratase and superoxide dismutase (SOD), hepatic SOD and hippocampus nitric oxide synthase while decreasing the blood lead level, the content of hepatic malondialdehyde and hippocampus nitric oxide; this was considered the optimal treatment group. There was no difference in the level of blood hemoglobin between the optimal treatment group and the model control group (the first group of the orthogonal experiment). The activities of blood glutathione (GSH), hepatic GSH and glutathione peroxidase of the optimal treatment group were the same as other groups', and the recovery of the related indexes in the optimal effect group closely resembled the high dosage DMSA group. It can be concluded that the coadministration of Fe, Zn, and chrysanthemum flavonoids along with a low-dose DMSA effectively reduces Pb poisoning and lead-induced oxidative damage in lead-exposed mice; the result may provide a theoretical reference for the treatment of Pb poisoning.

Keywords: DMSA; Pb poisoning; chrysanthemum flavonoids; combined treatment effect; nutrients.

MeSH terms

  • Animals
  • Calcium / administration & dosage
  • Calcium / pharmacology*
  • Chrysanthemum / chemistry*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Glutathione / blood
  • Glutathione Peroxidase / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Iron / administration & dosage
  • Iron / pharmacology*
  • Lead / adverse effects
  • Lead / blood
  • Lead Poisoning / drug therapy*
  • Liver / drug effects
  • Liver / metabolism
  • Malondialdehyde / metabolism
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Porphobilinogen Synthase / blood
  • Succimer / administration & dosage
  • Succimer / pharmacology*
  • Superoxide Dismutase / blood
  • Treatment Outcome
  • Zinc / administration & dosage
  • Zinc / pharmacology*

Substances

  • Flavonoids
  • Plant Extracts
  • Lead
  • Nitric Oxide
  • Malondialdehyde
  • Succimer
  • Iron
  • Glutathione Peroxidase
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Porphobilinogen Synthase
  • Glutathione
  • Zinc
  • Calcium