Histopathological Changes in the Kidney following Congestive Heart Failure by Volume Overload in Rats

Abstract

Background This study investigated histopathological changes and apoptotic factors that may be involved in the renal damage caused by congestive heart failure in a rat model of infrarenal aortocaval fistula (ACF). Methods Heart failure was induced using a modified approach of ACF in male Wistar rats. Sham-operated controls and ACF rats were characterized by their morphometric and hemodynamic parameters and investigated for their histopathological, ultrastructural, and apoptotic factor changes in the kidney. Results ACF-induced heart failure is associated with histopathological signs of congestion and glomerular and tubular atrophy, as well as nuclear and cellular degeneration in the kidney. In parallel, overexpression of proapoptotic Bax protein, release of cytochrome C from the outer mitochondrial membrane into cell cytoplasm, and nuclear transfer of activated caspase 3 indicate apoptotic events. This was confirmed by electron microscopic findings of apoptotic signs in the kidney such as swollen mitochondria and degenerated nuclei in renal tubular cells. Conclusions This study provides morphological evidence of renal injury during heart failure which may be due to caspase-mediated apoptosis via overexpression of proapoptotic Bax protein, subsequent mitochondrial cytochrome C release, and final nuclear transfer of activated caspase 3, supporting the notion of a cardiorenal syndrome.

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

“…Intriguingly, organ/body weight indices of the liver and kidney were not significantly altered in ACF rats which may be due to the large AV fistula itself that affects organ perfusion preventing it from increasing organ weight. Nonetheless, both organs showed overt histopathological changes in the liver [45] and kidney [46], as has been previously published. Secondly, this study was conducted to assess the indirect adverse opioidergic effects in cardiac volume overload.…”

Mitochondrial Dysfunction: An Emerging Link in the Pathophysiology of Cardiorenal Syndrome

“…CRS2 is defined as chronic cardiac insufficiency, leading to progressive manifestations of kidney damage, which contributes to the progression of CKD (155,156). Morphological studies in rat models of congestive HF-induced renal injury revealed mitochondrial swelling in renal tubular epithelial cells, possibly due to the release of Cyt-c, which mediated caspase 3 activation and nuclear transfer and triggered apoptosis, supporting the role of mitochondria-mediated apoptosis in CRS2 (145). Early empagliflozin treatment protects cardiac and renal function in CRS rats by reducing apoptin (mitochondrial-Bax/cleavedcaspase-3/cleaved-parp) and fibrosin (TGF-β/Smad3), reducing DNA/mitochondrial damage (γ-H2AX/cytoplasmic-Cyt-c), and maintaining mitochondrial function and integrity (146).…”

Protective Efficiency of Curcumin and Bone Marrow Mesenchymal Stem Cells of Nephrotoxicity Induced by Bromate in Rats

“…In this aspect, renal dysfunction induced by KBrO 3 in experimental animals characterized by tubular damage, loss of brush border, tubular necrosis, tubular dilatation, tubular cell swelling and glomerular injuries (Khan et al, 2010;Khan et al, 2012). Aboryag et al (2017) suggested that glomerular atrophy with widening of Bowman's space, epithelial shedding in tubular structures, pyknotic nuclei, desquamated cells, are indicators of apoptosis. This suggestion was confirmed in the present study by Tunnel assay which shows higher number of apoptotic cells in kidney of KBrO 3 treated rats.…”