Differential effects of cisplatin on mouse hepatic and renal mitochrondrial DNA

Abstract

The objective of this study was to determine if the nephrotoxic effects induced by cisplatin were correlated to mitochondrial DNA damage. Comparisons were made with the liver since hepatotoxicity is rarely observed. Cisplatin doses of 10, 20 and 40 mg/kg were administered intraperitoneally to C57BL/6J mice. Mitochondrial DNA was isolated from both the hepatic and renal tissues and quantitated by hybridization with a specific mitochondrial probe. Cisplatin caused differential effects on mouse hepatic and renal mitochondrial DNA. The 10 and 20 mg/kg dose caused an elevation in mitochondrial DNA levels in the hepatic, but no increase in the renal tissue was observed. This is the first study demonstrating an organ specific effect of cisplatin at the DNA level.

Pharmacokinetics and tissue distribution of novel traditional Chinese medicine-platinum anticancer agents in rats

“…Although relatively high amounts of Pt were found in the liver, a previous study by this research group found that none of the novel compounds caused undue hepatotoxicity [12]. One explanation might be the large storage capacity of the liver and its efficient detoxification by substances such as metallothioneins that are produced in large quantities [33]. Alternatively, it might be that most hepatocytes are resting in the G 0 phase, during which the cytotoxicity of Pt drugs is lower [18].…”

The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue

“…After the kidneys, cisplatin is mostly metabolized in the liver (Maniccia-Bozzo et al, 1990). Maniccia-Bozzo et al (1990) compared mitochondria in hepatocytes with platinum concentrations in nuclear regions and reported greater platinum metabolite concentration in mitochondria.…”

Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver

“…Additionally, in a study also performed with human autopsy tissues, Stewart et al (1985) suggested that cisplatin might be handled differently at the molecular level in the liver and in the kidney, since hepatic platinum concentration correlated with the dose of cisplatin, whereas renal platinum concentration did not. Maniccia-Bozzo et al (1990) demonstrated that cisplatin caused differential effects on mouse hepatic and renal mitochondrial DNA. Contrarily, our findings suggest a similarity between the molecular toxicity mechanisms induced by cisplatin in renal (Santos et al, 2007) and in hepatic mitochondria.…”