effect of experimentally induced oxidative stress on rat lung and the possible protective role of pentoxifylline: a histological and biochemical study

ABSTRACT

Acute lung injury and its most severe form, the acute respiratory distress syndrome are frequent complications in critically ill patients and are responsible for significant morbidity and mortality. Skeletal muscle breakdown [rhabdomyolysis] causes biochemical, functional and histological changes of kidney. The effects of rhabdomyolysis are likely mediated by increased oxidative stress leading to renal tubular cytotoxicity. Oxidative stress has a close relation to acute respiratory distress syndrome. This work was carried out to demonstrate the effect of experimentally induced oxidative stress on the lung histologically and biochemically and to study the role of pentoxii'lline in ameliorating these effects. Seventy adult male albino rats were used and divided into three main groups; the control [Group I] consisted of 20 rats and each experimental group consisted of 25 rats. Group II injected by i.m. glycerol once to induce rhabdomyolysis and consequently oxidative stress and group III received pentoxifylline before i.m glycerol injection. Heparinized blood samples were taken for assessment of total creatine kinase, total glutathione peroxidase, thiobarbituric acid reactive substances, plasma antioxidants, PaO[2] and PaCO[2]. Bronchoalveolar lavage [BAL] was taken for cellular profile and lung specimens for histological study. All samples were taken 6 hours after glycerol injection. Experimental group II showed significant increase in creatine kinase, total glutathione peroxidase and thiobarbituric acid reactive substance [TBARS]. Arterial blood gases showed significant decrease in PaO[2] and PaCO[2]. In BAL there was a significant increase in neutrophils and a non significant increase in macrophages. The lung showed increase in the thickness of the interalveolar septa with cellular infiltration associated with alveolar damage and many collapsed alveoli. Ultrastructurally, pneumocytes type II showed degenerative changes in the form of cytoplasmic vacuolation and destruction of lamellar bodies and mitochondria but in group III, all changes showed improvement with presence of minimal affection. Induced oxidative stress could lead to acute lung injury with biochemical alterations of many parameters. Meanwhile, pentoxifylline showed ameliorative effect on all of these parameters