Increased glutathione levels and activity of PON1 (phenyl acetate esterase) in the liver of rats after a single dose of cyclophosphamide: A defense mechanism?

Morphogenesis and Histostereological Analysis of Hepatopathy Induced by Cyclophosphamide

“…Our results indicate that CP caused signifi cant morphofunctional changes in the liver, similar to those caused by other antitumor drugs [5], despite the reports about slight damage infl icted to the liver by high-dose CP [8]. The major structural changes in the liver are small focal necroses of the parenchyma, disseminating from the portal tracts, paralleled by hypertrophy and hyperplasia of macrophageal cells.…”

“…Studies with repeated injections of low dose CP showed the pathogenetic role of exhaustion of the functional potentialities of the glutathione system, reduction of its intracellular reserves and subsequent impairment of the entire system of the hepatocyte antioxidant defense and stimulation of the free radical processes, this causing LPO intensifi cation and damage to membrane structures [2,9]. By contrast, a single injection of high dose (150 mg/kg) CP leads to an increase of glutathione level and stimulation of phenylacetatesterase [8], which can be regarded as a defense reaction. Hence, the choice of the optimal doses and treatment protocol for this drug and other cytostatics is essential for minimization of the toxic effect and triggering of the defense mechanisms (glutathione system, etc.…”

“…Some scientists think that the liver is least sensitive to toxicity of CP metabolites [8], while others claim that this organ is highly sensitive to the cytotoxic effect of CP [2]. The conclusions on CP hepatotoxicity are based mainly on the results of experiments with repeated low-dose (up to 20 mg/ kg) or single high-dose (150 mg/kg) injections of CP [7,8,14].…”

“…Some scientists think that the liver is least sensitive to toxicity of CP metabolites [8], while others claim that this organ is highly sensitive to the cytotoxic effect of CP [2]. The conclusions on CP hepatotoxicity are based mainly on the results of experiments with repeated low-dose (up to 20 mg/ kg) or single high-dose (150 mg/kg) injections of CP [7,8,14]. The morphogenetic processes induced by CP in the liver, the severity of cytotoxic effects towards hepatocytes and other cell populations, and the intensity of regeneratory reactions remain the least studied problems.…”

Protective role of Ipomoea obscura (L.) on cyclophosphamide-induced uro- and nephrotoxicities by modulating antioxidant status and pro-inflammatory cytokine levels

“…The clinical utility of CP is limited by its urotoxicity and nephrotoxicity (Hutter et al 1969;Mohrmann et al 1994). This drug induces acute inflammation of the urinary bladder, renal damage and less frequently, liver damage (Abraham and Sugumar 2008). From this study it was clear that treatment of Swiss albino mice with an extract from the plant I. obscura effectively eliminated the urotoxicity as well as nephrotoxicity induced by CP.…”