Acute Kidney Injury Induces Oxidative Stress and Hepatic Lipid Accumulation through AMPK Signaling Pathway

Abstract

Acute kidney injury (AKI) often impairs the function of other organs leading to distant organ injury. The liver is the major organ that regulates metabolism and lipid homeostasis in the body. It has been reported that AKI causes liver injury with increased oxidative stress, inflammatory response and steatosis. In the present study, we investigated the mechanisms by which ischemia-reperfusion-induced AKI caused hepatic lipid accumulation. Kidney ischemia (45 min)-reperfusion (24 h) led to a significant increase in plasma creatinine and transaminase in Sprague Dawley rats, indicating kidney and liver injury. Histological and biochemical analyses revealed hepatic lipid accumulation with a significant elevation of triglyceride and cholesterol levels in the liver. This was accompanied by a decreased AMP-activated protein kinase (AMPK) phosphorylation, indicating the reduced activation of AMPK, which is an energy sensor that regulates lipid metabolism. The expression of AMPK-regulated genes that were responsible for fatty acid oxidation (CPTIα, ACOX) was significantly decreased, while the expression of lipogenesis genes (SREPB-1c, ACC1) was significantly elevated. The oxidative stress biomarker malondialdehyde was elevated in the plasma and liver. Incubation of HepG2 cells with an oxidative stress inducer hydrogen peroxide inhibited AMPK phosphorylation and caused cellular lipid accumulation. This was accompanied by decreased expression of genes responsible for fatty acid oxidation and increased expression of genes responsible for lipogenesis. These results suggest that AKI elicits hepatic lipid accumulation through decreased fatty acid metabolism and increased lipogenesis. Oxidative stress may contribute, in part, to the downregulation of the AMPK signaling pathway leading to hepatic lipid accumulation and injury.

Acrylamide-Aggravated Liver Injury by Activating Endoplasmic Reticulum Stress in Female Mice with Diabetes

“…Impaired liver function affects the stability of the body’s metabolism. − The liver is not only one of the storage organs for lipids but also one of the main organs for the synthesis of fatty acids, cholesterol, and phospholipids. Excessive accumulation of lipids in the liver leads to severe impairment of its function. , In glucose metabolism, the liver can regulate blood glucose levels through hepatic glycogen synthesis, decomposition, and gluconeogenesis. However, excessive accumulation of hepatic glycogen also leads to abnormal enlargement of hepatocytes and impairment of normal liver function .…”

“…Excessive accumulation of lipids in the liver leads to severe impairment of its function. 27,28 In glucose metabolism, the liver can regulate blood glucose levels through hepatic glycogen synthesis, decomposition, and gluconeogenesis. However, excessive accumulation of hepatic glycogen also leads to abnormal enlargement of hepatocytes and impairment of normal liver function.…”

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“…Several studies have demonstrated that ROS can directly modulate lipogenesis at the signaling level. ROS such as hydrogen peroxide are known to activate signaling pathways that promote lipogenic gene expression [28]. Vitamin E inhibits lipogenesis by preventing the maturation of the SREBP-1 in HepG2 cells [16].…”

Evaluation Effects of Cefepime and Ceftriaxone on Renal Function Tests in Albino Male Rats

“…CaOx crystals have recently been shown to activate the NLRP3 inflammasome, which leads to progressive renal failure [25] Other studies found that cystine crystals, like CaOx, are endogenous inflammasome-activating stimuli [26] These findings on the molecular mechanisms of crystal-induced inflammation support a new perspective on crystal-related kidney injury. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) is the most extensively studied [27] , NLRP3 activates caspase-1 and pro inflammatory cytokines like IL-1β and IL-18 by assembling a multiprotein complex called the inflammasome, which includes a caspase recruitment domain (Asc) .The NLRP3 inflammasome is the most extensively studied of all inflammasomes [28] Numerous studies have found that oxidative stress can play an important role in the formation of kidney stones [29] urolithiasis, acute kidney injury was linked to ROS production and reduced antioxidant activity [30].…”