Metabolic Changes In Rats Research Articles

Exploring the metabolic implications of blue light exposure during daytime in rats

Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4 hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Significant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.

Synergistic Mechanism of stir-baked Curcumae Radix with Vinegar in Dysmenorrhea Rats Based on UPLC-Q-TOF/MS Metabolomics

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ with vinegar can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism is have not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the “LDQS” type, observation of blood rheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the potential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved blood rheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet.

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual's tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels.

Dried Blood Spots as Matrix for Evaluation of Valproate Levels and the Immediate and Delayed Metabolomic Changes Induced by Single Valproate Dose Treatment

The immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified. In male rats, changes in 2-hydroxybutyric acid, pipecolic acid, tetratriacontane and stearic acid were found between the control and treatment groups at various time points from 2.5 h up to 24 h. In contrast, such differences were not observed in female rats, which could be caused by the vast inter-individual variations in metabolite levels within the female group. Based on the measured DBS drug concentrations, clearance and apparent volume of distribution of VPA were estimated and the values were found to be comparable to those estimated previously from full blood drug concentrations. The current study indicated that DBS is a powerful tool to monitor drug levels and metabolic changes in response to drug treatment.

Oral magnesium sulphate administration in rats with minimal hepatic encephalopathy: NMR-based metabolic characterization of the brain

To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration. A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis. A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures. Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.

The Protective Effects of Trans-Anethole against Polycystic Ovary Syndrome Induced Histopathological and Metabolic Changes in Rat.

BackgroundAim of the study was to evaluate the protective effects of trans-anethole, against polycystic ovary syn- drome (PCOS) induced histopathological and biochemical changes in female Wister rats.Materials and MethodsIn this experimental study, forty-eight animals were randomly assigned into 6 groups: con- trol; PCOS; PCOS+trans-anethole (20, 40, 80 mg/kg); and PCOS+metformin (300 mg/kg). Testosterone (1 mg/kg/ day) was injected intraperitoneally for 35 days to induce PCOS. After PCOS induction, animals were treated by trans- anethole and metformin (30 days oral gavage). Finally, serum oxidative stress and insulin levels as well as histological changes in ovaries, kidneys and liver were evaluated.ResultsIn PCOS group, the serum level of malondialdehyde (MDA) was 1.391 ± 0.18 mmol/L and significantly increased (P=0.000) compared to the control group with the MDA level of 0.35 ± 0.08. Meanwhile the activity of superoxide dismutase (SOD) and catalase (CAT), and total thiol levels were significantly decreased (P=0.000 for all groups), compared to the control group. In the trans-anethole (80 mg/kg) treated group, insulin (P=0.000) and MDA (P=0.000) levels were significantly decreased while total thiol (P=0.001) and activity of SOD (P=0.000) and CAT (P=0.007) were significantly increased compared to the PCOS group. In the metformin treated group the insulin level (P=0.03) decreased compared to the PCOS group. Histological evaluation showed multiple cysts in the ovarian tissue, an increase in inflammatory cells in the liver, and a loss of order in the structure of the tubules and glomeruli of the kidney in the PCOS group. Tissue damage was reduced in the trans-anethole treated group.ConclusionTarns-anethole at a dose of 80 mg/kg improved metabolic status, oxidative stress, liver and kidney dam- age as well as the cystic mass of ovarian tissue. To understand the exact protective effects of trans-anethole in PCOS, more experimental or clinical studies are suggested.

Comprehensive analysis of metabolic changes in rats exposed to acrylamide

Acrylamide (ACR) is a widely used environmentally hazardous compound that is known to be neurotoxic, genotoxic, carcinogenic, and reproductive toxicity. It is widely present in soil, water, agents used in chemical industries, and food. It can be distributed to all organs and tissues, and can cause damage to various human systems and those of other animals. Previous metabolomics studies have mainly focused on metabolites in serum and urine, but have lacked comprehensive analysis of major organs and tissues. In the current study, a gas chromatography-massspectrometry method was used to investigate mechanisms underlying organ toxicity, in an effort to identify potentially sensitive biomarkers in the main target tissues of rats after ACR exposure. Male Sprague-Dawley rats were assigned to two groups; a control group and a group treated with 20 mg kg−1 ACR intragastrically for 6 weeks. Metabolite changes in the two groups were statistically analyzed. The respective numbers of altered metabolites in the hippocampus, cortex, kidney, serum, heart, liver, and kidney fat were 21, 21, 17, 5, 15, 14, and 6. There were 14 metabolic pathways related to amino acid, fatty acid, purine, and energy metabolism, revealing that the toxic mechanism of ACR may involve oxidative stress, inflammation, and amino acid metabolism and energy disorders.

Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats.

The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms.

Metabolic changes in the brain and blood of rats following acoustic trauma, tinnitus and hyperacusis.

It has been increasingly recognized that tinnitus is likely to be generated by complex network changes. Acoustic trauma that causes tinnitus induces significant changes in multiple metabolic pathways in the brain. However, it is not clear whether those metabolic changes in the brain could also be reflected in blood samples and whether metabolic changes could discriminate acoustic trauma, hyperacusis and tinnitus. We analyzed brain and serum metabolic changes in rats following acoustic trauma or a sham procedure using metabolomics. Hearing levels were recorded before and after acoustic trauma and behavioral measures to quantify tinnitus and hyperacusis were conducted at 4 weeks following acoustic trauma. Tissues from 11 different brain regions and serum samples were collected at about 3 months following acoustic trauma. Among the acoustic trauma animals, eight exhibited hyperacusis-like behavior and three exhibited tinnitus-like behavior. Using Gas chromatography-mass spectrometry and multivariate statistical analysis, significant metabolic changes were found in acoustic trauma animals in both the brain and serum samples with a number of metabolic pathways significantly perturbated. Furthermore, metabolic changes in the serum were able to differentiate sham from acoustic trauma animals, as well as sham from hyperacusis animals, with high accuracy. Our results suggest that serum metabolic profiling in combination with machine learning analysis may be a promising approach for identifying biomarkers for acoustic trauma, hyperacusis and potentially, tinnitus.

Effect of ginsenosides on serous metabonomic profiles in cerebral ischemia-reperfusion rats based on ~1H-NMR

Serum metabonomic profiles of the model of focal cerebral ischemia reperfusion is established with the suture-occluded method by Longa to study the effect of ginsenosides. In this study, 48 rats were randomly divided into six groups: sham-operated group, pathological model group, positive drug group(6 mg·kg~(-1)·d~(-1)) and high, medium, low-dose ginsenosides groups(200, 100, 50 mg·kg~(-1)·d~(-1)). They are given intragastric administration respectively with same amount of 0.5% CMC-Na,nimodipine and ginsenoside for 5 days. At 2 h after the final administration, the model was established with the suture-occluded method, and free radical-scavenging activity changes of ginsenoside were observed by maillard reaction, and Longa was possible used as a renoprotective agent-occluded method. At the end of 24 h after the reperfusion, the hemolymph of rats in each group was collected, and the ~1H-NMR spectrum was collected after being treated by certain methods, and analyzed by principal component analysis(PCA). Compared with sham-operated group, pathological model group showed significant increases in the levels of lactate, glutamate, taurine, choline, glucose and methionine, but decreases in the levels of 3-hydroxybutyrate and phosphocreatine/creatine in serum. After treatment with ginsenosides, lipid, 3-hydroxybutyrate and phosphocreatine/creatine were increased in the serum of ginsenosides group rats, but with decreases in lactate and glutamate. The results showed that ginsenosides could regulate metabolic disorders in rats with focal cerebral ischemia reperfusion, and promote a recovery in the process of metabolism. It's helpful to promote the metabolic changes in rats with focal cerebral ischemia reperfusion via ~1H-NMR, and lay a foundation to develop ginsenosides as a new drug to treat ischemic cerebral paralysis.

The Beneficial Effects of Stingless Bee Honey from Heterotrigona itama against Metabolic Changes in Rats Fed with High-Carbohydrate and High-Fat Diet.

Metabolic syndrome (MetS) is a group of conditions including central obesity, hyperglycemia, dyslipidemia, and hypertension that increases the risk for cardiometabolic diseases. Kelulut honey (KH) produced by stingless honey bees has stronger antioxidant properties compared to other honey types and may be a functional food against MetS. This study aimed to determine the efficacy of KH in preventing metabolic changes in rats with MetS induced by high-carbohydrate and high-fat (HCHF) diet. Male Wistar rats were randomly assigned to the control (C), HCHF diet-induced MetS (S), and MetS supplemented with KH (K) groups. The K group was given KH (1 g/kg/day) for eight weeks. Compared to the control, the S group had significant higher omental fat mass, serum triglyceride, systolic blood pressure, diastolic blood pressures, adipocyte area, and adipocyte perimeter (p < 0.05). KH supplementation significantly prevented these MetS-induced changes at week 16 (p < 0.05). Several compounds, including 4-hydroxyphenyl acetic acid, coumaric and caffeic acids, had been detected via liquid chromatography-mass spectrometry analysis that might contribute to the reversal of these changes. The beneficial effects of KH against MetS-induced rats provide the basis for future KH research to investigate its potential use in humans and its molecular mechanisms in alleviating the disease.

Integrative analysis of the gut microbiota and metabolome in rats treated with rice straw biochar by 16S rRNA gene sequencing and LC/MS-based metabolomics

The intestinal microbiota contributes to host metabolism and health. This study aimed to assess the effects of biochar on cecal microbiome-related metabolic changes in rats. Rats were orally administered rice straw biochar (RSB) at 1120 mg/kg body weight for 5 weeks. Cecal samples were analyzed to perform metabolic and microbial profiling via a combination of 16S rRNA gene sequencing and LC/MS techniques. We observed a significant influence of RSB in shaping the cecal bacterial community, including some potentially beneficial members of phylum Firmicutes belonging to unclassified Lachnospiraceae, Oscillibacter, and Clostridium XlVa and IV, as well as the depletion of some opportunistic pathogens belonging to Prevotella, Bacteroides and Paraprevotella. The metabolomic analysis revealed distinct changes in the cecal metabolic phenotype, including lower levels of L-isoleucine, indole-3-acetic acid, benzoic acid, and tetradecanoic acid as well as higher levels of L-phenylalanine, L-glutamate, 3-phenylpropanoic acid, chenodeoxycholic acid, cholic acid, 7-dehydrocholesterol, (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, 11-deoxycorticosterone and retinol, which are mainly involved in the metabolic pathways of linoleic acid, amino acid and steroid hormone biosynthesis. Correlation analysis revealed a positive association of unclassified Lachnospiraceae, Oscillibacter and Clostridium IV with 3-phenylpropanoic acid, L-phenylalanine, L-glutamate, 11-deoxycorticosterone and 7-dehydrocholesterol. These results confirm that the gut microbiome is altered and may be critical for good performance under RSB application by interacting with metabolism.

Effect of aqueous extract of olive leaves on some biochemical changes induced by carbon tetrachloride in male rats

Olive tree leaves have been widely used in traditional remedies in European and Mediterranean countries and in the human diet as extracts, herbal teas, and powder, which contain several potential bioactive compounds that may have antihypertensive, antiatherogenic, anti-inflammatory, hypoglycemic, hypocholesterolemic, antidiabetic and antioxidant activities. The present study was carried out to evaluate the role of olive leaves extracts (OLE) in ameliorating the metabolic changes in rats treated with carbon tetrachloride (CCl4). Forty-eight male rats were classified into six groups; the first group was the control which received 1 ml distilled water, the second group was treated daily with oral dose of cold OLE (1 ml/kg) for one month, the third group was treated daily with oral dose of boiled OLE (1 ml/kg) for one month, the fourth group was treated daily with oral dose of CCl4 (1 ml/kg) for one month, the fifth group was treated with both cold OLE and CCl4 (1 ml/kg for each) for one month and the sixth group was treated with both boiled OLE and CCl4 (1 ml/kg for each) for one month. Serum levels of thiobarbituric acid reactive substance (TBARS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), urea, creatinine, insulin and glutathione (GSH), catalase (CAT), albumin, total protein, free triiodothyronine (FT3) , free thyroxin (FT4) were measured in serum. Histological examination of hepatic tissue was examined. The results showed that administration of CCl4 to rats induced significant increase (P&lt;0.05) in serum levels of thiobarbituric acid reactive substance (TBARS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma- glutamyl transferase (GGT), lactate dehydrogenase (LDH), urea, creatinine, insulin and significant decrease (P&lt;0.05) in glutathione (GSH), catalase (CAT), albumin, total protein, free triiodothyronine (FT3) and free thyroxin (FT4). The histological examination of hepatic tissue showed some degenerative changes while significant improvement in biochemical and histological changes was observed either in CCl4 + cold OLE or CCl4 + boiled OLE groups. It could be concluded that the protective effect of olive leaves extract either cold or boiling may be attributed to its antioxidant properties. The obtained results indicated that both cold and boiled olive leaves extract has potent effect to restore the antioxidant status, hepato-renal function, insulin and thyroid hormones near to the control levels.

Mapping Changes of Whole Brain Blood Flow in Rats with Myocardial Ischemia/Reperfusion Injury Assessed by Positron Emission Tomography.

18F-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most sensitive tool for studying brain metabolism in vivo. We investigated the image patterns of 18F-FDG PET during reperfusion injury and correlated changes of whole brain blood flow utilizing a rat myocardial ischemia/reperfusion injury (MIRI) model. The results assessed by echocardiography indicated resultant cardiac dysfunction after ischemia-reperfusion in the rat heart. It was found that the average standardized uptake value (SUVaverage) of the whole brain was significantly decreased in model rats, and the glucose uptake of different brain regions including accumbens core/shell (Acb), left caudate putamen (LCPu), hippocampus (HIP), left hypothalamus (LHYP), olfactory (OLF), superior colliculus (SC), right midbrain (RMID), ventral tegmental area (VTA), inferior colliculus (IC) and left thalamus whole (LTHA) was significantly decreased in MIRI rats whereas no significant difference was found in the SUVaverage of amygdala (AMY), right CPu, RHYP, right HYP, left MID, right THA, pons and medulla oblongata (MO). These 18F-FDG PET data provide a reliable identification method for brain metabolic changes in rats with MIRI.

Структурно-метаболические изменения в скелетных мышцах крыс после повреждения спинного мозга

Структурно-метаболические изменения в скелетных мышцах крыс после повреждения спинного мозга

Chlorogenic acid attenuates high-carbohydrate, high-fat diet–induced cardiovascular, liver, and metabolic changes in rats

Chlorogenic acid as a constituent of coffee is consumed regularly in the human diet. Chlorogenic acid intake has been associated with decreased risk of cardiovascular disease and type 2 diabetes. We hypothesized that chlorogenic acid would improve cardiovascular, liver, and metabolic responses in a rat model of metabolic syndrome induced by a high-carbohydrate, high-fat diet. Male Wistar rats (8-9 weeks old, 335 ± 2 g, n = 48) were divided into 4 groups and fed with corn starch diet (16 weeks); corn starch diet with chlorogenic acid in food for the last 8 weeks; high-carbohydrate, high-fat diet (16 weeks); or high-carbohydrate, high-fat diet with chlorogenic acid (~100 mg/kg/d) in food for the last 8 weeks. In high-carbohydrate, high-fat diet–fed rats, chlorogenic acid reduced energy intake and food efficiency to reduce visceral fat, especially retroperitoneal fat, and abdominal circumference; reversed the elevated systolic blood pressure; and attenuated left ventricular diastolic stiffness with reduced collagen deposition and infiltration of inflammatory cells in the left ventricle. Chlorogenic acid decreased inflammation and fat deposition in the liver along with reduced plasma liver enzyme activities of obese rats but did not change the plasma lipid profile. Chlorogenic acid increased diversity of gut microbiota, which may improve overall metabolism in the body. Thus, chronic dietary chlorogenic acid attenuated diet-induced inflammation as well as cardiovascular, liver, and metabolic changes, suggesting that chlorogenic acid has potential for further clinical evaluation.

The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats

Acrylamide (ACR) is a hazardous substance associated with the accumulation of excessive reactive oxygen species and causes oxidative stress. Presence of ACR in foods leads to public health concerns due to its known neurotoxic, genotoxic, and carcinogenic effects. The present study investigated the ameliorative effects of boron (B) against ACR exposed rats. Forty Wistar albino male rats, fed with low-boron diet, were randomly and equally allocated into 5 groups. The control group was orally treated with physiological saline as placebo, the second group was orally given 15 mg/kg ACR. The other groups were orally treated with 15 mg/kg ACR and B at the levels of 5, 10, and 20 mg/kg/day for 60 days, respectively. ACR-treatment significantly increased malondialdehyde levels whereas decreased glutathione levels in rat tissues. Also, ACR-treatment increased the activities of superoxide dismutase and catalase in erythrocytes and tissues. Meanwhile, mRNA expression levels of NFĸB, IFN-γ, IL-1β, and TNF-α in liver and brain of rats were increased under ACR treatment. Additionally, ACR caused a significant decrease in the level of high-density lipoprotein, with increase in the levels of low-density lipoprotein, triglyceride, cholesterol, glucose, urea nitrogen, and creatinine. Lastly, B alleviated histopathological alterations induced by ACR in rat tissues.

Deciphering PPARγ activation in cardiometabolic syndrome: studies by in silico and in vivo experimental assessment

Cardiometabolic syndrome (CMetS) is a consolidation of metabolic disorders characterized by insulin resistance, dyslipidemia and hypertension. Curcumin, a natural bioactive compound, has been shown to possess notable anti-oxidant activity and it has also been included as a super natural herb in the super natural herbs database. Most of the beneficial effects of Curcumin are possibly due to activation of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigates molecular interactions of curcumin with PPARγ protein through molecular docking and molecular dynamics (MD) simulation studies. Further, effect of curcumin on high fat diet induced CMetS was studied in rats along with western blot for PPARγ and nuclear factor-κB (NF-κB) expressions and histopathological studies. Computational studies presented several significant molecular interactions of curcumin including Ser289, His323, His449 and Tyr473 of PPARγ. The in vivo results further confirmed that curcumin was able to ameliorate the abnormal changes and also, increased PPARγ expressions. The results confirm our hypothesis that activation of PPARγ by curcumin possesses the therapeutic potential to ameliorate the altered levels of metabolic changes in rats in the treatment of CMetS. This is the first report of CMetS treatment by curcumin and study of its underlying mechanism through in silico as well as in vivo experiments.

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity.

Brain Metabolic Changes in Rats following Acoustic Trauma

Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine metabolic pathway. Our results provide the first metabolomics evidence that acoustic trauma can induce changes in multiple metabolic pathways. This pilot study also suggests that the metabolomic approach has the potential to identify acoustic trauma-specific metabolic shifts in future studies where metabolic changes are correlated with the animal's tinnitus status.