Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats
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ORIGINAL PAPER
Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats Ansam Aly Seif & Doaa Mohamed Abdelwahed
Received: 6 October 2013 / Accepted: 2 April 2014 # University of Navarra 2014
Abstract Vitamin D, most commonly associated with the growth and remodeling of bone, has been shown to ameliorate ischemia/reperfusion injury (IRI) in some tissues, yet its underlying mechanism remains elusive. This study was designed to examine the protective effect of vitamin D, if any, against hepatic IRI in rats and the underlying mechanism involved. Adult female Wistar rats were randomly divided into control, sham-operated (sham), ischemia/reperfusion (I/R), and ischemicreperfused vitamin D-treated (vit D) groups. Rats in the I/R and vit D groups were subjected to partial (70 %) hepatic ischemia for 45 min, followed by 1 h of reperfusion. Vitamin D was given to rats orally in a dose of 500 IU/kg daily for 2 weeks before being subjected to I/R. Markers of liver damage, oxidative stress, inflammation and apoptosis were evaluated. Hepatic morphology was also examined. Vit D-treated rats had significantly lower serum levels of alanine aminotransferase, aspartate aminotransferase, and γ glutamyl transferase compared to rats in the I/R group. Also, vit D-treated rats showed a significant decrease in malondialdehyde, interleukin-1 beta, interleukin-6, tumor necrosis factor-α, nuclear factor κB, B cell leukemia/lymphoma 2-associated X protein, cytochrome c, and caspase-3 levels, with higher levels of glutathione peroxidase and B cell lymphoma 2 protein levels in liver tissues compared to I/R rats. Histological examination showed less damaged liver tissues with A. A. Seif (*) : D. M. Abdelwahed Faculty of Medicine, Ain Shams University, Cairo, Egypt e-mail: [email protected]
amelioration of apoptotic signs in the vit D group compared to the I/R group. In conclusion, vitamin D supplementation ameliorates hepatic IRI mostly by alleviating the inflammatory-apoptotic response mediated by the oxidative reperfusion injury insult. Keywords Vitamin D . Ischemia–reperfusion . Liver . Oxidative stress . Inflammation . Apoptosis
Introduction Ischemia–reperfusion injury (IRI) is a key contributing factor in liver dysfunction and failure being a major complication of hemorrhagic shock, resection, and transplantation [30]. It is a dynamic process that involves the two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury [30]. The redox balance, which is pivotal for normal function and integrity of tissues, is dysregulated during I/R, leading to accumulation of reactive oxygen species (ROS). Formation of ROS and oxidant stress is the disease mechanism most commonly invoked in hepatic IRI [9]. Apoptosis is also a central mechanism of IRI to the liver [13] since the coupling of inflammation and apoptosis in specialized cells and tissues is deemed fundamental in the pathogenesis of inflammatory diseases, including liver IRI [16]. Several therapeutic strategies, such as ischemic preconditioning, i
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