Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect

Abstract

This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

Short-term Menhaden Oil Rich Diet Changes Renal Lipid Profile in Acute Kidney Injury

“…The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. Thus, regardless of the presence or absence of choline, menhaden oil produces an upregulation of the Gstp1 gene, involved in the glutathione regeneration pathway as xenobiotic and antioxidant 29 .…”

Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3β signaling

“…Therefore, novel, safe, and effective approaches are urgently needed to prevent and treat AKI. Docosahexaenoic acid (DHA) and DHA-enriched fish oil were found to ameliorate kidney injury prophylactically and therapeutically in multiple animal models (6)(7)(8)(9). However, the mechanism underlying the reno-protection of DHA remains uncertain.…”

The impact of dietary choline-deprivation on kidneys and heart of stz-induced diabetic rats

“…Furthermore, kidneys play an essential role in homocysteine metabolism (Finkelstein, 2001); the aggravated renal necrosis under both metabolic insults might lead to the release of vitamin B12 from the necrotic renal tubules as it has been shown by increased serum vitamin B12 in necrotic kidneys (Scott et al, 1983) (Herber, 1997. Recent studies have shown an increase of the Gsp1 gene expression, an enzyme involved in homocysteine catabolism under dietary Ch-deficiency (Denninghoff et al, 2014), Histopathological evidence showed an exacerbation of renal tissue necrosis, mesengial matrix deposition and interstitial fibrosis in the diabetic rat kidney as a result of choline deprivation. The mechanism for CDrelated kidney injury is a relatively acute free-radical mediated process, quite similar to the hepatic necrosis following carbon paracetamol intoxication (Konstandi t al., 2009;Repetto et al, 2010;Yoon et al, 2016;Ossani et al, 2017).…”

“…The kidney is one of the most sensitive organ to choline deficiency along with the liver, heart, brain and eyes. Dietary choline deficiency is an experimental model of acute kidney injury (AKI) (Denninghoff et al, 2014). It has been observed that choline-deficiency (CD) induced by a choline-deficient diet develop acute kidney injury (AKI) with morphological alterations ranging from focal tubular necrosis to widespread cortical necrosis or reparative changes, renal failure and death in weanling male rats (Montes et al, 1980;Ossani et al, 2007).…”

“…It has been reported that the mechanism of Ch-deprivation inducing renal oxidative stress is mitochondrial complex syndrome I, which is quite similar to ischemic reperfusion-induced renal injury as well (Ossani et al, 2017). Ch-deficient diet results in an increased production of ROS, which is mainly responsible for oxidative damage in the kidney in a time and dose-dependent manner associated to a significant decline in tissue antioxidant capacity (Yoshida et al, 1993); conversely, antioxidant administration (e.g., butylated hydroxyanisole, butylated hydroxytoluene) has been shown to prevent the renal injury induced by Chdeficiency in adult rats ; furthermore, it has been revealed that Ch-deficient diet significantly upregulates Gstp1 gene expression in kidney (an enzyme involved in the metabolism of glutathione) (Denninghoff et al, 2014;Repetto et al, 2010;. The induced oxidative damage and lipid peroxidation by choline-deprivation appears before of the manifestation of histopathological changes but the oxidative damage continuous in a progressive manner in the rat Ossani et al, 2007;Repetto et al, 2010).…”