Abstract

Exposure to lead (Pb) can induce kidney injury and our recent studies have found that Salvia miltiorrhiza (SM) injection, a traditional Chinese medicine, could protect against the organ injury induced by iron overload. This study was designed to investigate the protective effects of SM injection on nephrotoxicity induced by Pb acetate in mice and to elucidate the potential mechanism(s). Healthy male mice were randomly divided into four groups: control, Pb, low-dose Salvia miltiorrhiza (L-SM), and high-dose Salvia miltiorrhiza (H-SM). SM injection dose dependently reduced the Pb accumulation in the kidney, decreased kidney coefficients, and ameliorated renal structure and function from the morphology analysis. Meanwhile, SM administration downregulated serum levels of blood urea nitrogen (BUN) and creatinine (CR), decreased malondialdehyde (MAD) content, and increased activities of super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the kidney homogenate. Moreover, SM injection reduced the level of renal apoptosis by immunohistochemical staining analysis. Our findings implicate the therapeutic potential of SM injection for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb accumulation, inhibition of lipid peroxidation, and suppression of renal apoptosis. These results provided preliminary experimental support for Danshen as a therapeutic drug for Pb poisoning diseases.

Highlights

  • Lead (Pb) is a common environmental contaminant and excessive exposure to it may cause chronic or acute nephrotoxic effects

  • By the Salvia miltiorrhiza (SM) injection treatment, the body weight of mice in both low-dose Salvia miltiorrhiza (L-SM) and high-dose Salvia miltiorrhiza (H-SM) groups was higher and the kidney coefficients were lower than the Pb group

  • Pb has been shown to inhibit the activities of antioxidant enzymes, including glutathione peroxidase (GSH-Px), catalase, and super oxide dismutase (SOD) [16]

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Summary

Introduction

Lead (Pb) is a common environmental contaminant and excessive exposure to it may cause chronic or acute nephrotoxic effects. Pb poisoning mainly inhibits cell enzymes that contained thiol and leads to the body’s biochemical and physiological dysfunction, causing small artery spasm and capillary endothelial cell injury, changing the properties of the normal erythrocyte membrane, inhibiting muscle phosphocreatine resynthesis, and so forth. This gives rise to a series of pathological changes, wherein the nervous system, the kidneys, and hematopoietic system are more remarkable. Clinical trials and epidemiological studies have demonstrated that lead poisoning can cause kidney damage Chelating agents such as disodium edetate calcium (EDTANa2Ca) and sodium dimercaptosuccinate (NaDMS) are commonly used in clinical to treat lead poisoning. Chelating agents form an insoluble complex with Pb for removal from the Pb-burdened tissue, but they are incapable of removing metal from intracellular sites and may cause

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