Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

Abstract

This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1β. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1β, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.

Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine

“…Moreover, the liver may be injured during the course of many diseases that are systemic or predominantly involve other organs, as sepsis, cardiovascular diseases (CVD), obesity, chronic kidney disease (CKD) and diabetes [ 35 ]. Despite the large number and variety of initiating factors, derived from extra- or intrahepatic environments [ 25 , 35 , 36 ], the final results are restricted, including death of hepatocytes or cholangiocytes leading, in severe cases, to the stereotyped anatomical and clinical patterns of portal hypertension, with or without cirrhosis [ 35 ].…”

Palmitate and pyruvate carbon flux in response to choline and methionine in bovine neonatal hepatocytes

“…In nonruminant species, the essential role of choline and Met to prevent lipidosis has been demonstrated and feeding choline-and Met-deficient diets is a common methodology to induce hepatic steatosis and lipidosis 5,6 . Deficiencies in these lipotropic nutrients may also contribute to lipidosis in ruminants 3 .…”

Persistent attenuation of brain oxidative stress through aging in perinatal maternal separated rat pups supplemented with choline and docosahexaenoic acid or Clitoria ternatea aqueous root extract

“…Choline supplements were also observed to lower exercise-induced lipid peroxidation and increase serum Vitamin A and E levels in women [47]. In turn, studies show that dietary deficiency of choline increases hydrogen peroxide production in liver mitochondria by causing lipid peroxidation of hepatocytes [48]. DHA is another supplement used in this study whose high levels in brain tissue have been shown to decrease brain lipid peroxidation [59] and when supplemented as combined eicosapentaenoic acid-docosahexaenoic it decreases lipid peroxidation and increases antioxidant enzyme activity in brain of hypercholesterolemic rats [52].…”

“…Administration of choline to women caused decrease in oxidative stress levels [47]. Dietary deficiency of choline increases lipid peroxidation in hepatocellular cells [48] and apoptosis in the foetal brain [9,60]. Similarly, docosahexaenoic acid (DHA) is another essential dietary nutrient.…”