Different role of Schisandrin B on mercury-induced renal damage in vivo and in vitro.

Abstract

Mercuric chloride (HgCl₂) causes acute oxidant renal failure that affects mainly proximal tubules. Schisandrin B (Sch B), an active lignan from the fruit of Schisandra chinensis, has been successfully used to treat gentamicin nephrotoxicity, but its role against mercury damage is still largely unknown. Here we analysed in vivo and in vitro the efficacy of Sch B supplementation against HgCl₂ nephrotoxicity, focusing on histopathology, stress proteins, oxidative (cytochrome c oxidase) and nitrosactive markers (eNOS, nNOS). Wistar rats were treated with Sch B (10 mg/kg/day p.o.) or vehicle (olive oil) for 9 days, then coadministered with a single HgCl₂ nephrotoxic dose (3.5 mg/kg i.p.) and killed after 24 h. The tubular and mitochondrial damage induced by mercury was limited by Sch B coadministration in vivo. Remarkably, after Sch B and mercury challenge, HSP25, HSP72, GRP75 were reduced in the renal cortex, cytochrome c oxidase increased and eNOS and nNOS were restored in glomeruli. In contrast, NRK-52E proximal tubular cells treated with Sch B 6.25 μM plus HgCl₂ 20 μM did not show any amelioration on viability and oxidative stress in respect to HgCl₂ 20 μM alone. Moreover, after Sch B plus mercury in vitro treatment, HSP72 staining persisted while HSP25 further increased. Thus, in our experimental conditions, Sch B cotreatment afforded better protection against mercury poisoning in vivo than in vitro. This discrepancy might be partly attributable to Sch B influence on glomerular perfusion as corroborated by the recovery of vasoactive markers like macular and endothelial nitric oxide isoforms.

• Authors: Alessandra Stacchiotti, Giovanni Li Volti, Antonio Lavazza, Ilaria Schena, Maria Francesca Aleo, Luigi Fabrizio Rodella, Rita Rezzani
• Journal: Toxicology (Toxicology) Vol. 286 Issue 1-3 Pg. 48-57 (Aug 15 2011) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 21616119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Cyclooctanes
• HSP27 Heat-Shock Proteins
• HSP70 Heat-Shock Proteins
• HSP72 Heat-Shock Proteins
• Hspb1 protein, rat
• Lignans
• Membrane Proteins
• Polycyclic Compounds
• glucose-regulated proteins
• schizandrin B
• Mercuric Chloride
• Cytochromes c
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type III

Topics

• Animals
• Cell Line
• Cyclooctanes (administration & dosage, pharmacology)
• Cytochromes c (drug effects, metabolism)
• Dose-Response Relationship, Drug
• HSP27 Heat-Shock Proteins (drug effects, metabolism)
• HSP70 Heat-Shock Proteins (drug effects, metabolism)
• HSP72 Heat-Shock Proteins (drug effects, metabolism)
• Kidney Cortex (drug effects, metabolism)
• Kidney Diseases (chemically induced, prevention & control)
• Kidney Tubules, Proximal (drug effects, pathology)
• Lignans (administration & dosage, pharmacology)
• Male
• Membrane Proteins (drug effects, metabolism)
• Mercuric Chloride (toxicity)
• Mitochondria (drug effects, pathology)
• Nitric Oxide Synthase Type I (drug effects, metabolism)
• Nitric Oxide Synthase Type III (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Polycyclic Compounds (administration & dosage, pharmacology)
• Rats
• Rats, Wistar