Effect of antisense oligodeoxynucleotides for ICAM‐1 on renal ischaemia–reperfusion injury in the anaesthetised rat

Abstract

An antisense oligodeoxynucleotide (As-ODN) to the 3 untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia-reperfusion injury in the rat. Wistar-Kyoto rats receiving I.V. either lipofectin-As-ODN (As-ODN group), lipofectin-reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three-to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia-reperfusion injury.

Macrophages in Renal Disease

“…39 Blockade of ICAM-1 with ODN also reduces macrophage infiltration and attenuates reperfusion injury in the rat. 40 However, inhibition of CCL2 using anti-CCL2 spiegelmers reduces macrophage infiltration, but does not improve renal pathology in mice with Alport nephropathy. 41 Specific genes have also been transferred to alter macrophage activation or inhibit signaling pathways.…”

Renal Ischemic Injury Affects Renal Hemodynamics and Excretory Functions in Sprague Dawley Rats: Involvement of Renal Sympathetic Tone

“…A similar pattern of change in GFR was observed in several earlier studies using this model. [14,16,[19][20][21] The possible reduction in GFR due to compromised RBF was further supported by the observation that there was a marked interstitial congestion, as was evident in the histopathological assessment of ischemic renal tissues, which would be consistent with increased renal vascular resistance.…”

“…These effects could be attributed to impaired urinary concentrating ability (at least in part), backleak of filtrate across the damaged proximal and distal tubular epithelia, and/or osmotic diuresis due to profound solutes loss. Despite the fact that the observed changes in the sodium and water excretions following renal ischemia/reperfusion have been reported in previous studies [14,16,19] and reaffirmed the effectiveness, reliability and reproducibility of animal model used, these reports did emphasize upon the correlation between sodium and potassium excretions following renal ischemic injury. Therefore, the present study extended previous findings to show that the rate of sodium excretion completely paralleled those of potassium and contributed to the absence of a statistically significant difference in U Na /U K in the early reperfusion phase following renal ischemia.…”

“…Ischemia was induced by clamping the left renal artery for 30 min followed by reperfusion. [14] Subsequently, the animals were subjected to one of the following protocols.…”

Sticky wickets in lower nephron nephrosis

“…In a paper in this issue of The Journal of Physiology, Kiew et al (2004) used an antisense oligodeoxynucleotide (ODN) for ICAM-1. Rats were exposed to a 30 min renal artery occlusion.…”