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

An Acad Bras Cienc. 2020;92(1):e20190261. doi: 10.1590/0001-3765202020190261. Epub 2020 May 11.

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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Cytarabine / adverse effects*
  • Male
  • NF-kappa B / analysis
  • Oxidants / blood
  • Oxidative Stress / drug effects
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / pathology
  • Rats
  • Rats, Wistar
  • Rutin / pharmacology
  • Rutin / therapeutic use*
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-kappa B
  • Oxidants
  • Tumor Necrosis Factor-alpha
  • Cytarabine
  • Rutin