Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Abstract

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 lg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-a) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-a, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Safety assessment of potential food ingredients in canine hepatocytes

“…Citric acid can attenuate lipopolysaccharide (LPS) induced liver injury including DNA fragmentation with a decrease of caspase-3 and serum transaminase elevations (Abdel-Salam et al, 2014). Our results have shown that citric acid has an LC50 of 1.58 ± 0.08 mg, which is not as toxic as the other components tested.…”

Dietary citric acid supplementation alleviates soybean meal-induced intestinal oxidative damage and micro-ecological imbalance in juvenile turbot,Scophthalmus maximusL

“…The present results were in accordance with previous studies on hypoxia/reoxygenation‐induced cardiomyocytes, which showed that citric acid significantly down‐regulated the gene expression of cleaved Caspase‐3 and decreased cell apoptotic rate (Tang et al, ). Abdel‐Salam et al () also provided evidence that citric acid significantly decreased the hepatic Caspase‐3 immunoreactivity in lipopolysaccharide‐treated mice. Involved in removal of intracellular ROS and repair of oxidative damage, p53 was reported to inhibit the cell proliferation and drive a temporary cell cycle arrest (Bensaad et al, ; Budanov, Sablina, Feinstein, Koonin, & Chumakov, ; Gatz & Wiesmüller, ; Sablina et al, ; Yoon, Nakamura, & Arakawa, ).…”

“…Similar results were observed in the study on large yellow croaker‐( Larimichthys crocea ) fed high doses of dietary plant protein, which showed that dietary citric acid alleviated intestinal oxidative damage (lipid peroxidation and oxidative carbonyl protein) through increasing intestinal T‐AOC and activities of SOD and Cu‐Zn SOD (Zhang et al, ). Another study on mice showed that ingestion of citric acid significantly attenuated LPS‐induced lipid peroxidation (in terms of MDA) in the brain tissue through increasing glutathione peroxidase (GPx) and paraoxonase 1 (PON1) activities (Abdel‐Salam et al, ). The increasing intestinal oxidative stress could cause the peroxidation of key biomolecules involved in various pathological processes including intestinal mucosal injury and digestive malfunctions (Ames, ; Halliwell, ; Jiang et al, ).…”

“…Several recent studies indicated that organic acids could alleviate oxidative stress status (Abdel-Salam et al, 2014;Ebrahimi et al, 2017;Li, Cui, & Leng, 2015;Romano et al, 2016;Zhang et al, 2016;Zhu, Qiu, Ding, Duan, & Wang, 2014). Besides, organic acids was also reported to beneficially modulate the intestinal microbiota and possess antimicrobial effects against several food-borne pathogens, such as Escherichia coli, Enterobacteria, Salmonella and Vibrio (Bosi et al, 1999;Canibe, Højberg, Højsgaard, & Jensen, 2005;Creus, Pérez, Peralta, Baucells, & Mateu, 2007;Partanen & Mroz, 1999;Silva, Vieira, Mouriño, Bolivar, & Seiffert, 2016;Zhou et al, 2009).…”

A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy

“…As one of the most important organic acids, citric acid (CA) is primary found in citrus fruits, such as lemon, grapefruit and orange (Abdel-Salam et al, 2014). CA is a type of a-hydroxy acid which has been widely used in food, beverage, chemical industries for many years (Xu et al, 2014).…”