Biochemical and Ultrastructural Lung Damage Induced by Rhabdomyolysis in the Rat

Abstract

Rhabdomyolysis-induced oxidative stress is associated with morphological and functional damage to the kidney and other organs, but applications of this model in the lung are still lacking. The aim of the present study was to determine the relationship between oxidative stress and the morphological changes occurring in the lungs of rats subjected to rhabdomyolysis. Rhabdomyolysis was induced by intramuscular glycerol injection (50% v/v, 10 ml/kg), and the control group was injected with saline vehicle. Arterial blood samples were drawn at 0, 2, 4, and 6 hrs for measurement of arterial gases, creatine kinase activity, and plasma free F2-isoprostane levels. Six hours later, the lungs were removed to determine the wet-to-dry weight ratio, reduced glutathione (GSH) and GSH disulfide (GSSG) levels, and activity of antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and GSH peroxidase [GSH-Px]). Protein carbonylation and lipid peroxidation were assessed in the lungs by measurement of carbonyl and malondialdehyde (MDA) production, respectively. Bronchoalveolar lavage, cell counts, and lung ultrastructural studies were also performed. Six hours after glycerol injection, arterial PO2 and PCO2 were 23% and 38% lower, respectively, and plasma free F2-isoprostane levels were 72% higher, compared with control values. In lungs, protein carbonyl and MDA production were 58% and 12% higher, respectively; the GSH:GSSG ratio and GSH-Px activity were 43% and 60% lower, respectively; and activities of CAT and SOD showed no significant differences compared with controls. Rhabdomyolysis-induced ultrastructural impairment of the lung showed Type II cell damage, extracytoplasmic lamellar bodies and lack of tubular myelin reorganization, endothelial cellular edema, and no disruption of the alveolar-capillary barrier. These results provide evidence that rhabdomyolysis could induce tissue injury associated with increased oxidative stress, suggesting the contribution of oxidative stress to the pathogenic mechanism of acute lung injury.

Intraperitoneal Glycerol Induces Oxidative Stress in Rat Kidney

“…The normal plasma CK activity levels in rats treated with i.p. glycerol indicates that rhabdomyolysis did not occur, because plasma CK activity is commonly used as a marker of muscular lesions and rhabdomyolysis 2,25 . Therefore, it is possible that glycerol may cause acute renal failure by mechanisms other than rhabdomyolysis.…”

Kidney-Lung Crosstalk in the Critically Ill Patient

“…For instance, in a rat model of rhabdomyolysis-induced oxidative stress, AKI was associated with increased permeability and inflammatory cell infiltration in the lung, and was accompanied by oxidative stress in the lung characterized by an increase in lipid peroxidation and F2-isoprostane as well as a decrease of antioxidant capacity such as reduced glutathione [35] . In addition, unilateral kidney IRI in both mice and rabbits has been shown to decrease distant organ hepatic levels of superoxide dismutase, catalase and glutathione, suggesting that ischemic AKI might compromise the host response to systemic oxidative stress [36,37] .…”

Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS

“…The remainder of BALF was centrifuged at 1500 rpm for 10 min at 4 °C, and the supernatant was removed. The BALF supernatant together with a plasma sample, which had been obtained from rat before taking BALF, were stored at -20 °C (Kim et al 2006;Rodrigo et al 2006 In the subgroup C of each group, changes in vascular permeability were assessed by quantitating extravasation of Evans blue dye (EBD) into the kidney and lung tissues.…”

“…The pulmonary circulation, which receives all cardiac output, responds to circulating factors released from other injured organs, with a resultant ALI (Ko et al 2009). There are several studies on rodents that demonstrate reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) play roles in the induction of ALI following ischemia/reperfusion (IR) injury in the hind limb (Punch et al 1991), intestine (Zhou et al 2003) and kidney (Campanholle et al 2010), as well as rhabdomyolysis-induced AKI (Rodrigo et al 2006). …”