Effect of Rutin on Cytarabine-Associated Pulmonary Oedema and Oxidative Stress in Rats.

Asli O Bilgin,Halis Suleyman,Mehmet Soyturk,Edhem Unver,Renad Mammadov,Bahadir Suleyman,Ferda K Cimen,Nezahat Kurt,Fatih Ozcicek

doi:10.1590/0001-3765202020190261

Asli O Bilgin, Halis Suleyman + Show 7 more

Open Access

https://doi.org/10.1590/0001-3765202020190261

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Abstract

Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.

Highlights

Cytarabine, a pyrimidine nucleoside analogue, has been in use in acute leukaemia treatment since 1964 (Barrios et al 1987, Patel et al 2012); it has many serious side effects, including neurotoxicity, myelosuppression, gastrointestinal mucosal damage and keratoconjunctivitis that can necessitate treatment cessation (Barrios et al 1987, Stentoft 1990)
The addition of rutin prevented the decrease in the tGSH level in the rutin+cytarabine group (17.7 ± 0.9 nmol/g protein) (p < 0.0001) (Fig. 3)
The radiological findings showed that pulmonary oedema developed in the rats administered cytarabine

Summary

Introduction

Cytarabine, a pyrimidine nucleoside analogue, has been in use in acute leukaemia treatment since 1964 (Barrios et al 1987, Patel et al 2012); it has many serious side effects, including neurotoxicity, myelosuppression, gastrointestinal mucosal damage and keratoconjunctivitis that can necessitate treatment cessation (Barrios et al 1987, Stentoft 1990). Severe or fatal pulmonary toxicity occurs in 12–20% of leukaemia patients given medium and high doses of cytarabine (Forghieri et al 2007). Cytarabine is reported to cause a form of pulmonary oedema that is unrelated to heart disease and cancer (Haupt et al 1981, Briasoulis & Pavlidis 2001), and its effects are dose related (Stentoft 1990). Free radical formation appears to play a role in the mechanism of this alveolar damage (Klausner et al 1991).

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