Cyclophosphamide-Associated Hepatotoxicity

Jw, Goldberg; Lidsky,

doi:10.1097/00007611-198502000-00034

Cited by 58 publications

(15 citation statements)

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“…CYP is known to cause multi organ injury that results in severe morbidity and death [40]. Most of the studies that focused on hepatotoxicity induced by CYP [35,38] did not elucidate any underlying mechanism. Previous studies have indicated that tissue damage results from a disturbance of the oxidation-antioxidation balance; production of oxygen free radicals and its oxidation product is one of the primary causes leading to hepatotoxicity [2,68,104].…”

Section: Discussionmentioning

confidence: 99%

“…A number of Indian medicinal plants of Ayurvedic origin have been experimentally claimed to possess immunomodulatory activity [3,66]. They activate humoral as well as cellular arms of the immune system of the host [59] through the stimulation of natural killer cells, B cells, T cells, and macrophage-dependent immune responses [5,34,35,53]. In addition to the growing concern on the research on plant extracts, there is also a rising interest on the action of isolated bioactive compounds on immunological liver injury.…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Duggina

Kalla

Varikasuvu³

et al. 2015

J Physiol Biochem

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This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Duggina

Kalla

Varikasuvu³

et al. 2015

J Physiol Biochem

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“…Of other antileukemic agents L-asparaginase and corticosteroids are associated with fatty infiltration of the liver [17][18][19]. There are only few reports of hepatic damage attributed to cyclophospamide [20,21] or doxorubicin [22]. In many of the previous studies viral hepatitis has obscured the hepatotoxic effects of the chemotherapeutic agents by inducing chronic liver disease in patients treated for leukemia [23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Halonen

Mattila

Ruuska

et al. 2003

Med. Pediatr. Oncol.

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“…Several reports have suggested that this drugs may also induce acute hepatitis and a lupus-like syndrome [133] . Finally, cyclophosphamide, an immunosuppressive and potent alkylating agent that improves the outcome of major organ disease when administered at high doses to SLE patients unresponsive to conventional therapy [134] , was reported to induce hepatotoxicity associated with liver inflammation in isolated cases [135,136] . There is a report of one case in the literature showing that this effect may occur even when the drug is administered at low doses [137] .…”

Section: Association Of Sle With Drug-induced Hepatotoxicitymentioning

confidence: 99%

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

Bessone

Poles

Roma

2014

WJH

106

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Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as "lupus hepatitis". In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g. , autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.

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Cyclophosphamide-Associated Hepatotoxicity

Cited by 58 publications

References 0 publications

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

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