Protective effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression

Life Sci. 2013 Apr 9;92(12):727-32. doi: 10.1016/j.lfs.2013.01.031. Epub 2013 Feb 9.

Abstract

Aims: Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP.

Main methods: Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined.

Key findings: CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice.

Significance: Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Benzylisoquinolines / therapeutic use*
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Cisplatin / toxicity*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / genetics
  • Kidney Diseases / prevention & control*
  • Male
  • Metallothionein / genetics*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Benzylisoquinolines
  • RNA, Messenger
  • cepharanthine
  • Metallothionein
  • Cisplatin