Dexamethasone Pretreatment Attenuates Lung and Kidney Injury in Cholestatic Rats Induced by Hepatic Ischemia/Reperfusion

Abstract

Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

Administration of BMSCs with Muscone in Rats with Gentamicin-Induced AKI Improves Their Therapeutic Efficacy

“…As a kind of glucocorticoids, dexamethasone was widely used in the clinical studies for the treatment of kidney injury [36]–[39]. In succession, its therapeutic function for different kidney injury animal models (cyclosporine A nephrotoxicity injury, ischemia/reperfusion injury, uranyl nitrate induced injury, endotoxin induced injury and gentamicin nephrotoxic injury) has been demonstrated, and associated mechanisms, such as ameliorating microvascular oxygenation and stabilizing TRPC6 expression and distribution, were also investigated by several groups [34], [40]–[45]. Therefore, it was chosen as the positive drug in our study.…”

Role of mineralocorticoid receptor/Rho/Rho-kinase pathway in obesity-related renal injury

“…29 Briefly, kidney samples were homogenized separately in 0.1  M NaCl, 0.05  M Tris-Cl and 2% (v v −1 ) Triton X-100 together with protease inhibitors (Roche Diagnostics, Melbourne, Australia). After centrifugation, the supernatants were collected and stored at −80 °C until assayed.…”

Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive function in mice

“…Researchers (Gedik et al, 2012;Li et al, 2012;Wang et al, 2012) have found that lung inflammatory injury and acute myocardial damage caused by I/R injury is related to the production of TNF-α after reperfusion. In a recent study, Zhou et al (2012) found that the expression of TNF-α and IL-1β in lung and kidney tissue was significantly increased after hepatic I/R. It was believed that there was progressive impairment of cognitive function in patients 2 to 7 days after surgery, peaking on the 4th or 5th day (Kilo et al, 2001), and it was considered that a different degree of surgical invasion had a different influence on the cognitive function of surgical patients (Müller et al, 2004).…”

“…The common causes for POCD were anesthesia and surgical trauma, especially cardiac surgery and neurosurgery, which usually lead to the ischemia/ reperfusion (I/R) injury. Hepatic surgery, which also can cause I/R injury, although causing distant organ injury such as to lung, intestine and kidney (Colletti and Green, 2006;Jildenstal et al, 2011;Kadkhodaee et al, 2012;Zhou et al, 2012), has not been studied much in that regard.…”