Effects of carnosine supplementation on markers for the pathophysiological development of metabolic dysfunction-associated steatotic liver disease in a diet-induced model.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

Carnosine supplementation and retinal oxidative parameters in a high-calorie diet rat model.

BACKGROUND: To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation. METHODS: Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed. RESULTS: TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05). CONCLUSION: The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers. TRIAL REGISTRATION: Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.

Tomato-Oleoresin Anti-Inflammatory Effect Recovers Obesity-Induced Cardiac Dysfunction by Modulating Myocardial Calcium Handling.

BACKGROUND/AIMS: Considering the importance of inflammation on obesity-related disorders pathogenesis, including cardiac dysfunction, the interest in natural anti-inflammatory therapeutic strategies has emerged. The lycopene is a carotenoid presents in tomato and red fruits that displays anti-inflammatory properties. In this sense, we will evaluate the anti-inflamma-tory effect of tomato-oleoresin supplementation on obesity- related cardiac dysfunction by modulating myocardial calcium kinetic. METHODS: Male Wistar rats were initially randomized into 2 experimental groups: (Control, n= 20) or high sugar- fat diet (HSF, n=20) for 20 weeks. At week 20th, once detected the cardiac dysfunction (cardiac remodeling, systolic and diastolic dysfunction) by echocardiography in HSF group, animals were randomly divided to begin the treatment with tomato-oleoresin, performing 4 groups: Control (n= 10); Control + tomato tomato-oleoresin supplementation (Control + Ly, n= 10); HSF (n= 10) or HSF + tomato tomato-oleoresin supplementation (HSF + Ly, n= 10). Tomato oleoresin was mixed with maize oil equivalent to 10mg lycopene/kg body weight (BW) per day and given orally, by gavage, every morning for a 10-week period. It was analyzed cardiac inflammatory parameters by the enzyme-linked immunosorbent assay (ELISA) and in vivo (echocardiography) and in vitro (studying isolated papillary muscles from the left ventricle) cardiac function. The groups were compared by Two-Way analysis of variance (ANOVA). RESULTS: The HSF diet induced cardiac dysfunction (FS(%) C: 60.4±1.3; C+Ly: 60.9±1.3; HSF: 51.7±1.3; HSF+Ly: 59.4±1.4) and inflammation (TNF-α: C:1.88±0.41; C+Ly: 1.93±1.01; HSF: 4.58±1.99; HSF+Ly: 2.03±0.55; IL-6: C:0.58±0.16; C+Ly: 0.40±0.16; HSF: 2.00±0.45; HSF+Ly: 0.53±0.26; MCP-1: C:0.31±0.08; C+Ly: 0.43±0.22; HSF: 1.54±0.32; HSF+Ly: 0.50±0.16). Tomato-oleoresin supplementation improved cardiac remodeling and dysfunction, cardiac inflammation and myocardial calcium kinetic. CONCLUSION: the anti-inflammatory effect of tomato-oleoresin supplementation treated the obesity-induced cardiac dysfunction by modulating myocardial calcium handling.

Comparative effects of acute-methionine loading on the plasma sulfur-amino acids in NAC-supplemented HIV+ patients and healthy controls.

In this study, an acute overloading of methionine (MetLo) was used to investigate the trassulfuration pathway response comparing healthy controls and HIV+ patients under their usual diet and dietary N-acetyl-L-cysteine (NAC) supplementation. MetLo (0.1 g Met/kg mass weight) was given after overnight fasting to 20 non-HIV+ control subjects (Co) and 12 HIV+ HAART-treated patients. Blood samples were taken before and after the MetLo in two different 7-day dietary situations, with NAC (1 g/day) or with their usual diet (UD). The amino acids (Met, Hcy, Cys, Tau, Ser, Glu and Gln) and GSH were determined by HPLC and their inflow rate into circulation (plasma) was estimated by the area under the curve (AUC). Under UD, the HIV+ had lower plasma GSH and amino acids (excepting Hcy) and higher oxidative stress (GSSG/GSH ratio), similar remethylation (RM: Me/Hcy + Ser ratio), transmethylation (TM; Hcy/Met ratio) and glutaminogenesis (Glu/Gln ratio), lower transsulfuration (TS: Cys/Hcy + Ser ratio) and Cys/Met ratio and, higher synthetic rates of glutathione (GG: GSH/Cys ratio) and Tau (TG: Tau/Cys ratio). NAC supplementation changed the HIV pattern by increasing RM above control, normalizing plasma Met and TS and, increasing plasma GSH and GG above controls. However, plasma Cys was kept always below controls probably, associatively to its higher consumption in GG (more GSSG than GSH) and TG. The failure of restoring normal Cys by MetLo, in addition to NAC, in HIV+ patients seems to be related to increased flux of Cys into GSH and Tau pathways, probably strengthening the cell-antioxidant capacity against the HIV progression (registered at http://www.clinicaltrials.gov , NCT00910442).

Plasma glutathione of HIV⁺ patients responded positively and differently to dietary supplementation with cysteine or glutamine.

OBJECTIVE: Patients with positivity for the human immunodeficiency virus (HIV⁺) present low concentrations of antioxidant nutrients, including total glutathione (GSH) and its precursors. We investigated the responses of the sulfur-containing amino acid pathway to cysteine and glutamine (Gln) dietary supplements in patients with HIV⁺ compared with healthy controls. METHODS: Twelve treated patients (six men and six women, 22-45 y old) and 20 healthy controls (10 men and 10 women, 20-59 y old) were randomly assigned to 7-d dietary supplements containing N-acetylcysteine (NAC; 1 g/d) or Gln (20 g/d), with a 7-d washout period ingesting their usual diet. Blood samples were drawn after an overnight fast. High-performance liquid chromatographic plasma analysis of sulfur-containing amino acids (methionine, homocysteine, cysteine, and taurine), GSH, oxidized GSH, and serine, glycine, glutamic acid, and Gln was carried out moments before and after 7-d supplementations. Statistical comparisons were undertaken between groups and between dietary supplements (P < 0.05). RESULTS: Patients with HIV⁺ showed higher oxidized GSH and lower concentrations of GSH and all amino acids except homocysteine. The HIV⁺ group responded to the NAC by increased levels of sulfur-containing amino acids and GSH and equalized taurine and GSH levels in the control group. The Gln supplements also equalized the levels of GSH, Gln, and glycine in the control group. CONCLUSION: An increase in GSH may be attained by NAC or Gln supplementation, with NAC acting by increasing cysteine levels and Gln likely acting by replenishing the glycine pool (trial registered at http://www.clinicaltrials.gov, identifier NCT00910442).

Associações do estado nutricional, homocisteinemia e suplementação de folato com a disfunção cognitiva de mulheres idosas / Associations of nutritional status, homocysteine and folate supplementation with cognitive impairment in elderly women / Asociaciones del estado nutricional, suplementación con ácido fólico y homocisteína con deterioro cognitivo en las mujeres mayores

Introdução: A hiperhomocisteinemia é o principal fator isolado da aterosclerose, além de constituir-se em potente fator pró-oxidante. Ambas as situações somam-se na etiologia da deficiência cognitiva do idoso. Objetivo: Investigar as implicações mentais da homocisteinemia e da sua suplementação oral de folato em idosas e verificar possíveis alterações nas concentrações de homocisteína e sua influência sobre os escores cognitivos e concentrações plasmáticas de glicose e lipídios destes indivíduos. Método: Foram estudadas 32 mulheres (70,2 + 4,8 anos) do grupo de intervenção (G1) e 24 (67 + 5,2 anos) do grupo controle (G2) todas submetidas, no momento inicial, a avaliação clínica, laboratorial, antropométrica, consumo alimentar e cognitiva (Mini Mental state Examination - MMSE). As avaliações foram repetidas, no grupo G1, após 60 dias ao término da suplementação de ácido fólico. Resultados: O grupo G1 era mais velho, com valores maiores de glicemia e menores de MMSE (p<0,05). Não houve correlação do MMSE com Hcy (r= 0,03) folato (r=0,152) e vitamina B12 (r=0,036). A suplementação de folato (G1) aumentou a folacemia, reduziu a homocisteinemia e a glicemia, com redução de 50% de hiperglicêmicos, assim como dos hiperhomocisteinêmicos, de 45,8% para 18,8%. As respostas à suplementação ocorreram no subgrupo com Hcy >13 mol/L, com elevação da folacemia, sem alteração do MMSE e da B12, e, no subgrupo MMSE <= 23, com elevação da folacemia e redução da homocisteinemia, sem alteração da B12. Conclusão: embora sem correlacionar-se com Hcy, folato ou vitamina B12, o MMSE deficitário responde positivamente ao tratamento nutricional redutor da hiperhomocisteinemia, com elevação da folacemia independentemente da vitamina B12.

Introduction: Hyperhomocysteinemia is a major factor isolated from atherosclerosis, besides being potent factor in pro-oxidant. Both situations are added to the etiology of cognitive impairment in the elderly. Objective: To investigate the implications of mental homocysteinemia and its oral folate supplementation in elderly women and to assess possible changes in the concentrations of homocysteine and its influence on cognitive scores and plasma concentrations of glucose and lipids of these individuals. Methods: We studied 32 women (70.2 + 4.8 years) in the intervention group (G1) and 24 (67 + 5.2 years) in the control group (G2) all submitted at the time initial clinical evaluation, laboratory, anthropometric, dietary intake and cognitive (Mini Mental State Examination - MMSE). The assessments were repeated, G1, 60 days after the end of the supplementation of folic acid. Results: The G1 group was older, with higher values of blood glucose levels and lower MMSE (p <0.05). There was no correlation of MMSE with Hcy (r = 0.03), folate (r = 0.152) and vitamin B12 (r = 0.036). Folate supplementation (G1) increased folacemia, homocysteinemia and decreased blood glucose, with 50% of hyperglycemic, and of hiperhmocisteinêmicos, 45.8% to 18.8%. Responses to supplementation occurred in the subgroup with Hcy> 13 mol/L, with elevated folacemia without changing the MMSE and B12, and in the subgroup MMSE <= 23, with elevated homocysteine and decreased folacemia, without changing the B12 . Conclusion: Although not correlate with Hcy, folate or vitamin B12, the MMSE deficit responds positively to the nutritional treatment of hyperhomocysteinemia reducer, with elevated folacemia regardless of vitamin B12.

Introducción: La hiperhomocisteinemia es un factor importante aislado de la aterosclerosis, además de ser factor potente en la pro-oxidante. Ambas situaciones se añaden a la etiología del deterioro cognitivo en los ancianos. Objetivo: investigar las consecuencias de homocisteinemia mental y su complementación con folato oral en mujeres de edad avanzada y para evaluar posibles cambios en las concentraciones de homocisteína y su influencia en los resultados cognitivos y las concentraciones plasmáticas de glucosa y los lípidos de estos individuos. Métodos: Se estudiaron 32 mujeres (70,2 + 4,8 años) en el grupo de intervención (G1) y 24 (67 + 5,2 años) en el grupo control (G2) presentados en su totalidad en el momento de la evaluación clínica inicial, laboratorio, antropométricas, la ingesta alimentaria y cognitiva (Mini Mental State Examination - MMSE). Las evaluaciones se repitieron, G1, 60 días después del final de la suplementación de ácido fólico. Resultados: El grupo G1 fue mayor, con valores más altos de los niveles de glucosa en la sangre y disminuyen MMSE (p <0,05). No se encontró correlación con los niveles de homocisteína de MMSE (r = 0,03), ácido fólico (r = 0,152) y vitamina B12 (r = 0,036). Suplementos de ácido fólico (G1) folacemia aumentado, homocisteinemia y la disminución de glucosa en la sangre, con un 50% de la hiperglucemia y de hiperhomocisteinêmicos, el 45,8% a 18,8%. Las respuestas a la suplementación se produjo en el subgrupo con Hcy> 13 mol / L, con folacemia elevados sin cambiar el MMSE y B12, y el subgrupo MMSE <= 23, con la homocisteína elevada y la disminución de folacemia, sin cambiar el B12 . Conclusión: Si bien no se correlacionan con los niveles de homocisteína, ácido fólico o de vitamina B12, el déficit MMSE responde positivamente a la reducción de tratamiento nutricional de hiperhomocisteinemia con folacemia elevados independientemente de la vitamina B12.