Cyclophosphamide-impaired regulation of hepatic heme metabolism

Abstract

In male rats hepatic cytochromes b5 and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a 'non-cytochromal' form. Parallel to the above changes the heme metabolism showed derangement: delta-aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.

In vitro gene expression analysis of hepatotoxic drugs in rat primary hepatocytes

“…Decreased Cyp3a3 (Table 3C) was consistent with a previous in vivo study in rats, whereas no increases of Cyp2b or Cyp2c, which have been reported in the in vivo study (Xie et al, 2005), were observed. Increased Hmox1 may be consistent with a previous report that showed increased heme oxygenase content in the liver in rats in vivo (Rizzardini et al, 1984).…”

Anticancer therapy in patients with porphyrias: evidence today

“…Cyclophosphamide was not found to be porphyrinogenic in mice. In previous studies, the effect of cyclophosphamide on the haem metabolic pathway in rats and rabbits was inconsistent [45,46] . A number of patients with variegate porphyria have received cytotoxic chemotherapy without suffering a porphyric crisis [47][48][49] .…”