The Hepatic Antioxidant System Damage Induced with the Cafeteria (CAF) Diet Is Largely Counteracted Using SCD Probiotics during Development of Male Wistar Rats.

The cafeteria (CAF) diet, reflective of predominant Western dietary behaviors, is implicated in hastening weight gain, subsequently resulting in health complications such as obesity, diabetes, and cancer. To this end, it is vital to notice the deleterious consequences of the CAF regimen prior to the onset of complications, which is fundamental for early intervention in the context of numerous diseases. Probiotic-derived postbiotic metabolites have gained attention for their antioxidative properties, offering a potential countermeasure against oxidative stress. This research sought to discern the protective efficacy of SCD Probiotics against liver glutathione system damage arising from the CAF diet during developmental phases. Male Wistar rats, from weaning on day 21 to day 56, were categorized into four groups: a control on a conventional diet; a group on a standard diet enriched with SCD Probiotics; a mixed-diet group comprising both CAF and standard feed; and a combination diet group supplemented with SCD Probiotics. Through the application of real-time PCR, enzyme activity assessments, and quantitative metabolite analyses, our findings highlight the CAF diet's adverse influence on the liver's antioxidant defenses via shifts in gene expression. Yet, the inclusion of SCD Probiotics mostly ameliorated these harmful effects. Remarkably, the positive regulatory influence of SCD Probiotics on the liver's antioxidant system was consistently observed, independent of the CAF diet's presence.

Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice.

Tat-interactive protein 60 kDa (TIP60, also known as lysine acetyltransferase 5 [KAT5]) is a member of the MYST protein family with histone acetyltransferase activity. Recent studies have reported that TIP60 has multiple functions in many signal transduction mechanisms, especially p53-mediated apoptosis. Although the activation of apoptosis signaling pathways requires the presence of cellular reactive oxygen species (ROS) at a certain level, an imbalance between the production and consumption of ROS in cells results in oxidative stress (OS). In this study, we investigated for the first time how the absence of the Tip60 gene in the liver affects gene expression, enzyme activity, and protein expression of the hepatic antioxidant members localized in the cytoplasm, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST). First, we successfully generated liver-specific Tip60 knockout mice (mutants) using Cre/LoxP recombination. The reduced glutathione level and nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) expression, a marker of OS, increased significantly in the Tip60 mutant liver. Gene expression, activity, and protein expression of the enzymatic antioxidant system, including SOD, CAT, GR, GPx, and GST were investigated in mutants and control groups. Despite a significant correlation between the gene, enzyme activity, and protein content for CAT and GR, this was not true for SOD and GPx. The overall results suggest that TIP60 acts on the hepatic antioxidant system both at the gene and protein levels, but the actual effect of the deletion of Tip60 is observed at the protein level, especially for SOD and GPx.

Postbiotic metabolites, antioxidant and anticancer activities of probiotic Leuconostoc pseudomesenteroides strains in natural pickles.

In this study, five strains of Leuconostoc pseudomesenteroides were thought to have probiotic properties and anticancer activity isolated from natural pickles and identified by performing the 16S rRNA sequence analysis. The probiotic properties, postbiotic amounts, the capacity to adhere to the L-929, HT-29 and Caco-2 cell lines, the effects of postbiotic and bacterial extracts on cell viability and biochemical activities were investigated in the strains. In the results, Leu. pseudomesenteroides Y6 strain was detected to have the best resistance to the stomach and intestinal environments, and the quantities of postbiotic metabolites are similar to each other. The bacterial adhesion capacities were found to be in the range of 1.66-8.5%. Furthermore, postbiotic metabolites of all isolates had good anticancer activity (27.67-86.05%) and the activity of bacterial extractions increased depending on concentration. Leu. pseudomesenteroides Y4 and Y6 strains generally showed better activity than controls and all strains were strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavengers in the antioxidant studies. In conclusion, the Y6 strain, which had the best probiotic feature, was found to show significantly good biological activity. It is thought that this isolate will be supported by new in vivo studies and eventually be brought to the food and health industry.

Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice.

BACKGROUND: Carbonic anhydrases (CAs) play a significant role in maintaining pH balance by catalyzing the conversion of carbon dioxide to bicarbonate. The regulation of pH is critical for all living organisms. Although there are many studies in the literature on the biochemical, functional, and structural features of CAs, there is not sufficient information about the epigenetic regulation of CAs. METHODS AND RESULTS: The lysine acetyltransferase TIP60 (60 kDa Tat-interactive protein) was knocked out specifically in mouse liver using the Cre/loxP system, and knockout rate was shown as 83-88% by Southern blot analysis. The impact of Tip60 on the expression of Ca1, Ca3, and Ca7 was investigated at six Zeitgeber time (ZT) points in the control and liver-specific Tip60 knockout mice (mutant) groups by real-time PCR. In the control group, while Ca1 showed the highest expression at ZT8 and ZT12, the lowest expression profile was observed at ZT0 and ZT20. Hepatic Ca1 displayed robust circadian expression. However, hepatic Ca3 exhibited almost the same level of expression at all ZT points. The highest expression of Ca7 was observed at ZT12, and the lowest expression was determined at ZT4. Furthermore, hepatic Ca7 also showed robust circadian expression. The expression of Ca1 and Ca3 significantly decreased in mutant mice at all time periods, but the expression of Ca7 used as a negative control was not affected. CONCLUSIONS: It was suggested for the first time that Tip60 might be considered a candidate protein in the regulation of the Ca1 and Ca3 genes, possibly by acetylation.

Effect of a Prolonged Dietary Iron Intake on the Gene Expression and Activity of the Testicular Antioxidant Defense System in Rats.

Despite the fact that iron represents a crucial element for the catalysis of many metabolic reactions, its accumulation in the cell leads to the production of reactive oxygen species (ROS), provoking pathological conditions such as cancer, cardiovascular diseases, diabetes, neurodegenerative diseases, and fertility. Thus, ROS are neutralized by the enzymatic antioxidant system for the purpose of protecting cells against any damage. Iron is a potential risk factor for male fertility. However, the mechanism of action of iron on the testicular antioxidant system at the gene and protein levels is not fully understood. Thus, the purpose of the current research was to ensure a better understanding of how the long-term iron treatment influences both gene expression and enzyme activities of the testicular antioxidant system in rat testis. The data of our study showed that a significant dose-dependent increase occurred in the iron level in rat testis. A reduction occurred in reduced glutathione (GSH) levels, which represent a marker of oxidative stress, along with long-term iron overload. The expression and activity of glucose 6-phosphate dehydrogenase (G6pd), glutathione reductase (Gr), glutathione peroxidase (Gpx), and glutathione S-transferases (Gst) were significantly affected by the presence of iron. The findings of the current research demonstrate that the long-term toxic dietary iron overload influences the gene expression and enzyme activity of the testicular antioxidant defense system, but the actual effect occurs at the protein level. This may modify the sperm function and dysfunction of the male reproductive system.

The Effects of Amoxicillin, Cefazolin, and Gentamicin Antibiotics on the Antioxidant System in Mouse Heart Tissues.

BACKGROUND: Free radicals lead to destruction in various organs of the organism. The improper use of antibiotics increases the formation of free radicals and causes oxidative stress. OBJECTIVE: In this study, it was aimed to determine the effects of gentamicin, amoxicillin, and cefazolin antibiotics on the mouse heart. METHODS: 20 male mice were divided into 4 groups (1st control, 2nd amoxicillin, 3rd cefazolin, and 4th gentamicin groups). The mice in the experimental groups were administered antibiotics intraperitoneally at a dose of 100 mg / kg for 6 days. The control group received normal saline in the same way. The gene expression levels and enzyme activities of SOD, CAT, GPx, GR, GST, and G6PD antioxidant enzymes were investigated. RESULTS: GSH levels decreased in both the amoxicillin and cefazolin groups, while GR, CAT, and SOD enzyme activities increased. In the amoxicillin group, Gr, Gst, Cat, and Sod gene expression levels increased. CONCLUSION: As a result, it was concluded that amoxicillin and cefazolin caused oxidative stress in the heart, however, gentamicin did not cause any effects.

Examining the link between dose-dependent dietary iron intake and Alzheimer's disease through oxidative stress in the rat cortex.

BACKGROUND: Neurodegenerative diseases such as Alzheimer's and Parkinson's disease are characterized by the progressive deterioration of the structure and function of the nervous system. A number of environmental risk factors including potentially toxic elements such as iron, lead to negative effects on many metabolic reactions as well as neuroprotection. The aim of this study is to reveal whether long-term iron overload is one of the underlying factors in the pathogenesis of Alzheimer's disease (AD). METHODS: 15 young-adult male rats were randomly divided into 5 groups treated with iron through drinking water for 4 months. Following feeding, the iron content, reduced glutathione (GSH), and hydrogen peroxide (H2O2) levels of cortex tissues were measured. Specific enzyme activities were determined spectrophotometrically. mRNA expression profiles were measured using real-time PCR (qPCR). RESULTS: Iron levels were elevated in case of non-toxic (0.87 and 3 µg/mL) iron administration. However, no changes were observed in toxic (30 and 300 µg/mL) iron administration. GSH and H2O2 levels altered with long-term iron overload. Glutathione peroxidase (GPx) enzyme activities significantly increased in all groups, while glutathione S-transferase (GST) activity increased only in case of 0.87 and 30 µg/mL iron administration. Expression levels of neuroprotective and AD-related genes were altered by 3 µg/mL iron overload in a dose-dependent manner. The expression and activity of acetylcholinesterase (AChE) were elevated at 3 µg/mL iron concentration. CONCLUSION: The findings of the present study allow us to conclude that long-term dietary iron intake, especially at a dose of 3 µg/mL demonstrates negative effects on the rat cortex by provoking antioxidant metabolism and AD pathology in a dose-dependently.

In vitro and in vivo effects of iron on the expression and activity of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase in rat spleen.

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long-term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level.

Stimulation of gene expression and activity of antioxidant related enzyme in Sprague Dawley rat kidney induced by long-term iron toxicity.

The trace elements such as iron are vital for various enzyme activities and for other cellular proteins, but iron toxicity causes the production of reactive oxygen species (ROS) that causes alterations in morphology and function of the nephron. The present study was designed to determine the effect of long-term iron overload on the renal antioxidant system and to determine any possible correlation between enzymatic and molecular levels. Our data showed that reduced glutathione (GSH) levels, which is a marker for oxidative stress, strikingly decreased with a long-term iron overload in rat kidney. While renal mRNA levels of glucose 6-phosphate dehydrogenase (G6pd), 6-phosphogluconate dehydrogenase (6pgd) and glutathione peroxidase (Gpx) were significantly affected in the presence of ferric iron, no changes were seen for glutathione reductase (Gsr) and glutathione S-transferases (Gst). While the iron affected the enzymatic activity of G6PD, GSR, GST, and GPX, it had no significant effect on 6PGD activity in the rat kidney. In conclusion, we reported here that the gene expression of G6pd, 6pgd, Gsr, Gpx, and Gst did not correlate to enzyme activity, and the actual effect of long-term iron overload on renal antioxidant system is observed at protein level. Furthermore, the influence of iron on the renal antioxidant system is different from its effect on the hepatic antioxidant system.

Expression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in oxidative stress induced by long-term iron toxicity in rat liver.

Reactive oxygen species (ROS) are highly reactive and oxygen-containing molecules that are derived by metabolic activities or from environmental sources. Toxicity of heavy metals including iron has the ability to generate ROS in all living organisms. The pentose phosphate pathway enzymes, which are glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, produce nicotinamide adenine dinucleotide phosphate (NADPH) that enables cells to counterbalance the oxidative stress via the action of the glutathione system. The results presented here have shown that toxic and nontoxic levels of iron have a strong effect on the expression of both genes. While toxic levels of iron exhibited significant changes in enzyme activity, nontoxic levels had no effect on enzymes in rat liver. Our results are the first evidence to elucidate how oxidative stress induced by long-term iron toxicity affects both enzymes at the enzymatic and molecular level and also to determine any possible correlation between the enzymatic and molecular levels.

Impact of long term Fe³âº toxicity on expression of glutathione system in rat liver.

The free radicals within the body, produced by metabolic activities or derived from environmental sources are relatively related to hepatoxicity. Since heavy metals including iron have the ability to produce free radicals, the liver glutathione system neutralizes them to protect cells against any damage. The objective of this study is to indicate the toxic effects of iron on the glutathione system at the enzymatic and molecular level. Thus, any possible correlation between enzymatic and molecular levels can be determined. According to our results, while mRNA expression of glutathione reductase (Gsr) and glutathione S-transferases (Gsta5) genes were not affected by long-term exposure to various concentrations of iron (Fe(3+)), transcription level of glutathione peroxidase (Gpx2) was influenced in the presence of toxic iron. Whereas the enzyme activites of GSR (GR), GPX and GST were significantly affected in rat liver.