Glutamic Pyruvic Transaminase Research Articles

Short-term repeated oral intake of low dose cannabidiol: effects on liver enzyme activity and creatinine concentration during intense exercise.

The side effects and safety of cannabidiol (CBD) products are currently discussed in different contexts. Of all adverse effects, hepatotoxic effects have been reported most frequently in previous studies. However, the threshold for liver toxicity of CBD in humans is uncertain due to the lack of adequately designed studies in humans below the lowest observed adverse effect level (LOAEL) of 300 mg/day. In a randomised, three-arm, double-blind, crossover study, the effects of two CBD products (oil and solubilisate (solu) containing 60 mg CBD) were investigated during a high-intensity exercise protocol. Seventeen well-trained subjects (26±4 years, 181±5 cm, 85.6±9.4 kg) participated in the intervention. All subjects were healthy and had no physiological or psychological injuries. Participants were divided into advanced (Ad) and highly advanced (Hi) athletes … They consumed 60 mg of the compound in each microcycle over 7 days. To evaluate possible effects of short-term repeated use of 60 mg CBD on oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), gamma-glutamyl transferase (GGT) and creatinine (CREA) were analysed before and after each microcycle. GOT increased significantly in both performance levels of the placebo groups (Ad: p≤0.001; Hi: p=0.003). This increase was significantly reduced in the Ad group by both CBD oil (p=0.050, ES=0.66) and CBD solu (p=0.027; ES=0.75). GPT also increased significantly in both placebo groups (Ad: p≤0.001; Hi: p=0.032). This increase was significantly reduced in the Ad group by both CBD oil (p=0.027; ES=0.75) and CBD solu (p=0.023; ES=0.77). These effects were not observed in the Hi group for either parameter. Our results show that short-term repeated use of 60 mg CBD can inhibit exercise-induced liver activity. Furthermore, under the conditions of the present study, there was no evidence for hepatotoxic effects of oral intake of CBD at 60 mg for seven days. Nevertheless, despite the inhibitory effect on exercise-induced liver activity, the study provides evidence for the pharmacological effects of CBD on the liver even at low CBD dose and does not exclude adverse effects in sensitive individuals.

Molecular pathways of osmoregulation in response to salinity stress in the gills of the scalloped spiny lobster (Panulirus homarus) within survival salinity

Scalloped spiny lobster (Panulirus homarus) aquaculture is the preferred strategy to resolve the conflict between supply and demand for lobster. Environmental conditions, such as salinity, are key to the success of lobster aquaculture. However, physiological responses of P. homarus to salinity stress have not been well studied. This study investigated the gill histology, osmoregulation and gill transcriptome of the early juvenile P. homarus (weight 19.04 ± 3.95 g) cultured at salinity 28 (control), 18, and 38 for 6 weeks. The results showed that the gill filaments of P. homarus exposed to low salinity showed severe separation of the cuticle and epithelial cells due to water absorption and swelling, as well as the dissolution and thinning of the cuticle and the rupture of the septum that separates the afferent and efferent channels. The serum osmolarity of P. homarus varied proportionately with external medium salinity and remained consistently above ambient osmolarity. The serum Na+, Cl−, K+, and Mg2+ concentrations P. homarus exhibited a pattern similar to that of serum osmolality, while the concentration of Ca2+ remained unaffected at salinity 18 but significantly increased at salinity 38. Gill Na+/K+-ATPase activity of P. homarus increased (p < 0.05) under the both salinity stress. Salinity 18 significantly increased Glutamate dehydrogenase (GDH) and Glutamicpyruvic transaminase (GPT) activity in the hepatopancreas of P. homarus (p < 0.05). According to transcriptome analysis, versus control group (salinity 28), 929 and 1095 differentially expressed genes (DEGs) were obtained in the gills of P. homarus at salinity 18 and 38, respectively, with these DEGs were mainly involved in energy metabolism, transmembrane transport and oxidative stress and substance metabolism. In addition, the expression patterns of 8 key DEGs mainly related to amino acid metabolism, transmembrane transport and oxidative stress were verified by quantitative real-time PCR (RT-qPCR). The present study suggests that salinity 18 has a greater impact on P. homarus than salinity 38, and P. homarus demonstrates effective osmoregulation and handle with salinity fluctuations (18 to 38) through physiological and functional adaptations. This study provides an improved understanding of the physiological response strategies of P. homarus facing salinity stress, which is crucial for optimizing aquaculture practices for this species.

Detection of Some Heavy Metals (Mercury and Lead) Pollutants and their Association with Type 2 Diabetes Mellitus (T2DM) in Baghdad, Iraq

Due to the increased use of products carrying heavy metals caused by human factors in the streets of the city of Baghdad and their direct impact on the air, water quality and soil pollution, heavy metals pollution is one of the important environmental problems. As heavy metals cannot be degraded, they accumulate biologically, and, therefore, can directly threaten higher organisms including humans. The current study focused on detecting heavy metals (mercury and lead) to determine the adverse effects and risk of developing type 2 diabetes mellitus (T2DM) in humans. One hundred total blood samples were collected from healthy people and the patients of both sexes who were suffering from T2DM, with mean age of 31 to 75 years, after 8 to 12 hours of fasting. The first group - G1 the control group consisted of 20 health people (6 males and 14 females). The second group - G2 included 40 patients (20 males and 20 females) who had T2DM and were not exposed to any pollutants. The third group - G3 included 40 males with T2DM and also who were exposed to smoke from local electricity generators, as these samples were collected from workers or living near generators and were exposed to air pollution for a long time. Blood samples were collected from each individual by drawing blood from a vein to evaluate each of the biochemical tests, as well as detecting of some heavy metals such as mercury and lead. The results showed that there was a highly significant increase (p≤0.01) when both fasting blood sugar (FBS) and HbA1c were analysed. As for the results of the analysis of the types of lipid profile, there is no significant difference in cholesterol, while there was a significant increase (p≤0.05) in both low-density lipoprotein (LDL) cholestrol and very low density lipoprotein (VLDL) cholestrol and a highly significant increase (p≤0.01) for both triglyceride and high density lipoporotein cholesterol (HDL) cholestrol. The results of the liver function analysis showed that there was no significant difference in the results of the enzyme serum glutamic oxaloacetic transaminase (SGOT) as well as total bilirubin, while there was a significant increase (p≤0.05) in serum glutamate pyruvate transaminase (SGPT). Significant increase (p≤0.01) was detected in the alkaline phosphatase (ALP) enzyme for each of the studied groups. The results of the detection of the presence of heavy metals using the atomic absorption spectrophotometer showed that there was a significant increase (p≤0.01) in lead, and as for mercury, no significant difference was noticed.

Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism

Recessive loss-of-function mutations in the mitochondrial enzyme Glutamate Pyruvate Transaminase 2 (GPT2) cause intellectual disability in children. Given this cognitive disorder, and because glutamate metabolism is tightly regulated to sustain excitatory neurotransmission, here we investigate the role of GPT2 in synaptic function. GPT2 catalyzes a reversible reaction interconverting glutamate and pyruvate with alanine and alpha-ketoglutarate, a TCA cycle intermediate; thereby, GPT2 may play an important role in linking mitochondrial tricarboxylic acid (TCA) cycle with synaptic transmission. In mouse brain, we find that GPT2 is enriched in mitochondria of synaptosomes (isolated synaptic terminals). Loss of Gpt2 in mouse appears to lead to reprogramming of glutamate and glutamine metabolism, and to decreased glutamatergic synaptic transmission. Whole-cell patch-clamp recordings in pyramidal neurons of CA1 hippocampal slices from Gpt2-null mice reveal decreased excitatory post-synaptic currents (mEPSCs) without changes in mEPSC frequency, or importantly, changes in inhibitory post-synaptic currents (mIPSCs). Additional evidence of defective glutamate release included reduced levels of glutamate released from Gpt2-null synaptosomes measured biochemically. Glutamate release from synaptosomes was rescued to wild-type levels by alpha-ketoglutarate supplementation. Additionally, we observed evidence of altered metabolism in isolated Gpt2-null synaptosomes: decreased TCA cycle intermediates, and increased glutamate dehydrogenase activity. Notably, alterations in the TCA cycle and the glutamine pool were alleviated by alpha-ketoglutarate supplementation. In conclusion, our data support a model whereby GPT2 mitochondrial activity may contribute to glutamate availability in pre-synaptic terminals, thereby highlighting potential interactions between pre-synaptic mitochondrial metabolism and synaptic transmission.

Laboratory Biochemical and Hematological Parameters: Early Predictive Biomarkers for Diagnosing Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is a worldwide concern, causing liver damage and necessitating early detection to prevent its spread. Studies indicate that evaluating changes in biochemical and hematological parameters, which serve as suitable predictors of inflammation, can be a reasonable method for diagnosing hepatitis C infection. This study analyzed 100 samples from high-risk patients positively identified via quantitative real-time PCR (qPCR). Anti-HCV titers, biochemical and inflammatory tests, and complete blood cell counts (CBCs) were performed for these individuals. Additionally, 100 HCV-negative individuals with normal laboratory results were selected as the control group. Receiver operating characteristic (ROC) curves were plotted to determine the cutoff values of the laboratory parameters. According to the findings, the age, average white blood cell (WBC) count, platelet-to-lymphocyte ratio (PLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and ferritin levels were significantly higher in HCV patients. On the other hand, red blood cell (RBC) counts, neutrophils, lymphocytes, hemoglobin-to-platelet ratio (HPR), and iron (Fe) levels were significantly lower in the case group compared to those in the control group (p < 0.05). Furthermore, the ROC curve analysis revealed that lymphocyte count, neutrophil count, and PLR were very strong predictors for hepatitis C infection (p < 0.0001, AUC = 1). The study highlights significant biochemical and hematological differences between HCV patients and healthy subjects. These biomarkers are crucial for early diagnosis, potentially preventing liver damage and reducing HCV transmission.

Liver Manifestations in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and their impact on quality of life

Abstract Background ADPKD is the most prevalent monogenic kidney disease with an estimated incidence of 1:1000. The condition is characterized by the formation of kidney cysts, which can cause kidney function loss and bears a significant risk of advancing to kidney failure. This study examined the prevalence of hepatic cysts in individuals with ADPKD, and the possible influence of these cysts on liver function and quality of life. Furthermore, the relationship between hepatic cysts and genotype was analysed. Methods Clinical data from 880 patients with ADPKD were analysed, including longitudinal patient data, genetic information, and laboratory parameters. Results The prevalence of hepatic cysts in adult ADPKD patients was 81.71%, consistent with previous studies. Prevalence increased with age, particularly in male patients. No clear association was observed between ADPKD genotype and the presence of liver cysts. Among male patients with liver cysts, glutamic-pyruvic transaminase (GPT) levels significantly decreased with age, while female patients showed a significant increase in gamma-glutamyl transferase (γ-GT) levels. Overall, hepatic cysts had minimal impact on liver enzymes. Quality of life assessments using the SF-12 questionnaire revealed no significant influence of hepatic cysts on physical or mental well-being. However, physical quality of life was significantly lower in patients showing polycystic liver disease as a manifestation of ADPKD compared to all other patients, both with and without liver cysts. Conclusions Hepatic cysts are highly prevalent in adult patients with ADPKD, increasing with age. ADPKD genotype does not appear to be associated with the presence of hepatic cysts. Liver function, as indicated by enzyme levels, is minimally affected by hepatic cysts in most ADPKD patients. The quality of life of ADPKD patients is generally unaffected by the presence of hepatic cysts, except in severe cases of polycystic liver disease (PLD). Further research is needed to develop effective treatments for severe PLD and gain a better understanding of the factors influencing hepatic cyst incidence and progression in patients with ADPKD.

Cold-Pressed Aristotelia chilensis (Mol.) Stuntz Seed Oil Prevents Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat-Diet-Induced Obesity Murine Model.

This study evaluated the effects of cold-pressed maqui (Aristotelia chilensis (Mol.) Stuntz) seed oil (MO) on liver metabolism and biochemical markers in a high-fat diet (HFD) murine model. In it, the fatty acid profile, tocopherol and tocotrienol contents, and antioxidant capacity of MO were analyzed. Male C57BL/6 mice were divided into four groups (i.e., a, b, c, and d groups) and supplemented for 12 weeks according to the following distribution: (a) control diet (CD)-sunflower oil (SO), (b) CD+MO, (c) HFD+SO, and (d) HFD+MO. Total body and organ weights, serum markers, and liver fat infiltration were assessed. MO contained 32.31% oleic acid, 46.41% linoleic acid, and 10.83% α-linolenic acid; additionally, α- and γ-tocopherol levels were 339.09 ± 5.15 and 135.52 ± 38.03 mg/kg, respectively, while β-, δ-tocopherol, and α-tocotrienol were present in trace amounts and the antioxidant capacity measured was 6.66 ± 0.19 μmol Trolox equivalent/g. MO supplementation significantly reduced the visceral fat (0.76 ± 0.06 g vs. 1.32 ± 0.04 g) and GPT (glutamate pyruvate transaminase) levels (71.8 ± 5.0 vs. 35.2 ± 2.6 U/L), and the liver fat infiltration score (6 vs. 3) in the HFD+MO group compared to HFD+SO. It is suggested that MO may effectively prevent fatty liver disease, warranting further research on its potential benefits for human health.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Comparative Transcriptome Analysis Reveals the Impact of a High-Fat Diet on Hepatic Metabolic Function in Tilapia (Oreochromis niloticus).

Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a normal control (Ctr)-fed group and a high-fat diet (HFD)-fed group. Serum biochemical analyses revealed that HFD feeding led to liver damage and lipid accumulation, characterized by elevated levels of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), triglycerides (TGs), and total cholesterol (TC). Transcriptome analysis showed that 538 genes were significantly downregulated, and 460 genes were significantly upregulated in the HFD-fed fish. Gene Ontology (GO) enrichment analysis showed that these differentially expressed genes (DEGs) were apparently involved in the lipid metabolic process and monocarboxylic acid metabolic process. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated significant alterations in pathways of steroid biosynthesis, porphyrin metabolism, terpenoid backbone biosynthesis, and retinol metabolism after HFD feeding. Additionally, results from Gene Set Enrichment Analysis (GSEA) revealed that gene expression patterns in pathways including oxidative phosphorylation, protein export, protein processing in the endoplasmic reticulum, and ribosome biogenesis were positively enriched in the HFD-fed tilapia. These findings provide novel insights into the mechanisms underlying HFD-induced hepatic dysfunction in fish, contributing to the optimization of feeding strategies in aquaculture.

Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism.

Recessive loss-of-function mutations in the mitochondrial enzyme Glutamate Pyruvate Transaminase 2 (GPT2) cause intellectual disability in children. Given this cognitive disorder, and because glutamate metabolism is tightly regulated to sustain excitatory neurotransmission, here we investigate the role of GPT2 in synaptic function. GPT2 catalyzes a reversible reaction interconverting glutamate and pyruvate with alanine and alpha-ketoglutarate, a TCA cycle intermediate; thereby, GPT2 may play an important role in linking mitochondrial tricarboxylic acid (TCA) cycle with synaptic transmission. In mouse brain, we find that GPT2 is enriched in mitochondria of synaptosomes (isolated synaptic terminals). Loss of Gpt2 in mouse appears to lead to reprogramming of glutamate and glutamine metabolism, and to decreased glutamatergic synaptic transmission. Whole-cell patch-clamp recordings in pyramidal neurons of CA1 hippocampal slices from Gpt2- null mice reveal decreased excitatory post-synaptic currents (mEPSCs) without changes in mEPSC frequency, or importantly, changes in inhibitory post-synaptic currents (mIPSCs). Additional evidence of defective glutamate release included reduced levels of glutamate released from Gpt2- null synaptosomes measured biochemically. Glutamate release from synaptosomes was rescued to wild-type levels by alpha-ketoglutarate supplementation. Additionally, we observed evidence of altered metabolism in isolated Gpt2- null synaptosomes: decreased TCA cycle intermediates, and increased glutamate dehydrogenase activity. Notably, alterations in the TCA cycle and the glutamine pool were alleviated by alpha-ketoglutarate supplementation. In conclusion, our data support a model whereby GPT2 mitochondrial activity may contribute to glutamate availability in pre-synaptic terminals, thereby highlighting potential interactions between pre-synaptic mitochondrial metabolism and synaptic transmission.

The influence of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra on rat liver function and structure

Background. Tea mistletoe (Scurrula atropurpurea (Blume)) and mango mistletoe (Dendrophthoe pentandra) have been known as a potential medicine for several diseases.Objective: to investigate the effect of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra (MESA-DP) on rat liver function and structure using serological and histopathological analysis.Material and methods. This study was experimental during 28 days using 20 rats divided into four groups (Group 1 as a control, while Groups 2, 3, and 4 were given MESA-DP at doses 250, 500, and 1,000 mg/kg of body weight, respectively). The liver histopathological structure was observed using hematoxylin-eosin staining. The liver function assessment included total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Data were analyzed using a one-way ANOVA analysis (ANalysis Of VAriance) and performed via SPSS Statistics 17.0 (IBM, USA).Results. The administration of MESA-DP did not show significant differences at all doses for the liver rat function in total bilirubin, SGOT, SGPT, albumin, cholesterol and triglycerides (p&gt;0.05), while globulin, total protein, HDL and LDL showed significant results (p&lt;0.05). The liver histopathological structure showed the number of pyknotic, karyorrhectic and karyolytic cells in rats after MESA-DP administration compared to controls, which grew with increasing dose.Conclusion. The liver function in rats after being exposed to MESA-DP was not affected in terms of total bilirubin, SGOT, SGPT, albumin, cholesterol, and triglyceride levels. However, using MESA-DP increased the necrotic liver cells. It may be beneficial for the liver health of experimental animals taking into account the correct dosage.

Efficacy of Cytoreg in the treatment of diabetic foot disease.

Complications from diabetic foot wounds, including bacterial infection, ulceration and gangrene, are major causes of hospitalisation and are responsible for 85% of amputations in patients with diabetes. Given that orally administered investigational therapeutic Cytoreg (Cytorex de Venezuela SA, Venezuela), a defined aqueous mixture of hydrofluoric, hydrochloric, sulfuric, phosphoric, citric and oxalic acids, has been shown to increase levels of arterial blood oxygen in a Wistar rat model, oral and oral+topical Cytoreg were tested on patients with diabetic foot ulcers (DFUs) under a humanitarian, compassionate-use protocol. All patients received oral Cytoreg (5.0 ml concentrate in fruit juice) for 30 days; half also received weekly wound washing with Cytoreg concentrate in isotonic saline (1:50 volume/volume) (oral+topical group). In addition to standard clinical observations, wounds were monitored against the Saint Elian checklist system for the diabetic foot. A total of 10 patients took part in the study. Complete wound closure was observed in 4/5 patients in the oral+topical group; in the remaining patient, necrotic and fibrin tissues on the wound edges were eliminated. Half (2/4) of the patients receiving oral-only Cytoreg experienced complete wound closure; one patient in this group was removed prematurely because of an unrelated illness and was not replaced. During the study, no significant differences were observed between groups in either the oxygen saturation of the affected tissues or in insulin and glycaemia levels (p<0.05). Significant increases in arterial haemoglobin and arterial oxygen partial pressure (p<0.05) were observed, and significant decreases were measured in the levels of glycosylated haemoglobin, aspartate aminotransferase, glutamic-pyruvic transaminase, creatine and urea (p<0.05). The results of this study justify an expanded clinical study for the treatment of DFUs with Cytoreg.

The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.

Sine oculis homeobox homolog 1 (SIX1) is a new identified cancer driver in the development of prostate cancer (PC). However, the upstream regulatory mechanisms for SIX1 reactivation in cancer remains elusive. Here, we found that Ku70 robustly interacts with SIX1 in the nucleus of PC cells. The HD domain of SIX1 and the DBD domain of Ku70 are required for formation of Ku70-SIX1 complex. 20 groups of hydrogen bonds were identified in this complex by molecular dynamics simulation. Depletion of Ku70/SIX1 notably abrogates the proliferation and migration of PC. Further studies revealed that SIX1 is recruited to the promoter region on glutamate-pyruvate transaminase 2 (GPT2). Ku70 enhances the SIX1-mediated transcriptional activation on GPT2, thereby facilitating the generation of alpha-ketoglutarate (α-KG). In addition, formation of the Ku70-SIX1 complex promotes GPT2-dependent cell proliferation and migration in PC. Moreover, the expression of GPT2 is upregulated and strongly correlated with the expression of Ku70/SIX1 in PC tissues. In summary, our findings not only provide insight into the mechanistic interactions between Ku70 and SIX1, but also highlight the significance of the Ku70-SIX1-GPT2 axis for α-KG metabolism and PC carcinogenesis.

Histological and Biochemical Evaluation of Silibinin in Treatment of Periodontitis Induced in Rats with Liver Cirrhosis.

This study aimed to evaluate the impact of silibinin as a therapeutic agent on ligature-induced periodontitis in rats with liver cirrhosis. Twenty-five Wistar rats were enrolled in this study. Group A (Control) included eight rats. The other 17 rats received CCl4 to develop cirrhosis, which was confirmed by sacrificing one of the rats and performing a histological examination of its liver tissue. Periodontitis was induced in the remaining 16 rats then they were allocated into (n = 8) group B-periodontitis with cirrhosis and group C-silibinin-treated group, 5 times/week starting from week 11 till week 14. Animals of the three groups were euthanized, and biochemical analysis comprising of liver functions assessment (serum levels of glutamate-pyruvate transaminase, serum levels of glutamate-oxalate transaminase, TIMP1) and oxidative stress index [MDA, nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT)] and histological examination were conducted by the end of week 14. Group C revealed a more organized orientation of the periodontal ligament (PDL) collagen fibers with a marked regain of the alveolar bone height compared to group B. Biochemical analysis confirmed the potent therapeutic effect of silibinin manifested by a significant improvement in the biochemical parameters: tissue inhibitor of metalloproteinase-1, MDA, NO levels, and antioxidant enzymes. Group B was associated with the most unfavorable biochemical findings and the maximum periodontal destruction. Group C demonstrated a positive osteogenic capacity and a noteworthy improvement in biochemical findings, which were comparable to those of group A, which displayed normal and healthy findings. The study highlights the potential use of silibinin as a natural remedy with minimal side effects for treating periodontitis in rats with liver cirrhosis. The findings could be translated to human clinical trials, which may lead to new treatment strategies using silibinin as a targeted therapy or as adjunctive therapy to conventional periodontal treatment for patients with liver cirrhosis who are more susceptible to periodontitis. How to cite this article: Shawky HA, Ahmed NM, Essawy MM, et al. Histological and Biochemical Evaluation of Silibinin in Treatment of Periodontitis Induced in Rats with Liver Cirrhosis. J Contemp Dent Pract 2024;25(7):631-638.

Acute Febrile Illness in India: An Epidemiological Retrospective Study.

Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population. This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for bio-chemical analysis, with subsequent data analysis conducted using statistical methods. The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above. Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients.

Enhanced Antidiabetic Effects of Gymnema sylvestre and Probiotics in Alloxan-Induced Diabetic Rats

Abstract Introduction/Objective Introduction: Gymnema sylvestre is a well-known herbal remedy for diabetes, with its anti-diabetic properties attributed to gymnemic acids isolated from its leaves. Probiotics, such as Lactobacillus acidophilus and Lactobacillus casei, have also shown potential in managing diabetes. This study aims to evaluate the combined antidiabetic effects of G. sylvestre and probiotics in alloxan-induced diabetic rats. Methods/Case Report Methods: Experimental rats were divided into seven groups: negative control, untreated diabetic control, L. acidophilus-treated, L. casei-treated, G. sylvestre-treated, a combination of L. casei and G. sylvestre-treated, and a combination of L. acidophilus and G. sylvestre-treated. Blood glucose levels, lipid profiles, and reduced glutathione levels were measured, and histopathological examination of pancreas and kidney tissues was performed. Results (if a Case Study enter NA) Results: In the third week of the experiment, the combined administration of G. sylvestre and probiotics showed the most significant reductions in glucose levels (250 mg/dL), alkaline phosphatase (ALP) (613.3 U/L), urea (31 U/L), serum creatinine (0.77 U/L), and superoxide dismutase (SOD) (854.7 UMOL). G. sylvestre alone exhibited the lowest levels of glutamate pyruvate transaminase (GPT) (30 U/L), cholesterol (41 mg/dL), triglycerides (101.3 mg/dL), very-low-density lipoprotein (VLDL) (22.9 mg/dL), and malondialdehyde (MDA) (119.3 U MOL/SEC). Probiotic treatment alone resulted in the lowest levels of uric acid (UA) (4.4 U/L) and low-density lipoprotein (LDL) (95.06 mg/dL). G. sylvestre demonstrated the highest level of high-density lipoprotein (HDL) (44 mg/dL), while probiotics exhibited the highest catalase (CAT) activity (92 UMOL/SEC). Histopathological examination revealed the preservation of normal pancreatic and renal tissue morphology with G. sylvestre treatment. Conclusion Conclusion: The combination of G. sylvestre and probiotics enhances the antidiabetic activity compared to G. sylvestre alone in alloxan-induced diabetic rats. These findings suggest a potential synergistic effect of combining herbal and probiotic therapy for diabetes management.

Fibroblast growth factor 1 (FGF1) improves glucose homeostasis, modulates gut microbial composition, and reduces inflammatory responses in rainbow trout (Oncorhynchus mykiss) fed a high-fat diet

High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4D. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3β axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1β, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.

“Copper-loaded microplastics unleash endoplasmic reticulum stress-driven liver apoptosis in fish Channa punctatus”

The extensive use of plastics has led to significant microplastic pollution, posing threats to environmental and human health. Concerns are growing about the toxicity of microplastics (MPs) and their ability to adsorb contaminants like Copper (Cu2+). Therefore, this study investigated the effects of environmentally realistic concentrations of Polyvinyl Chloride (PVC)-MPs and Copper, both individually and together, with a particular focus on triggering Endoplasmic reticulum (ER) stress-driven apoptosis in the liver of Channa punctatus. Well-habituated fish were organized into four groups: Group I (Control), Group II (0.5 mg/L PVC-MPs), Group III (0.85 mg/L Copper), and Group IV (0.5 mg/L PVC-MPs + 0.85 mg/L Copper). The treatment period was 15, 30, 45 and 60 days. Various liver parameters were assessed according to standard protocols to understand the repercussions of intoxication. A significant (p < 0.05) increment in Reactive Oxygen Species (ROS) pointed to a substantial rise in oxidative stress. Enzymatic antioxidants like superoxide dismutase (SOD) and catalase (CAT) showed significantly (p < 0.05) elevated extents while reduced glutathione (GSH) levels significantly (p < 0.05) dropped in a duration-dependent pattern. Additionally, lipid peroxidation (LPO) activities surged significantly (p < 0.05), and notable hepato-structural disruptions were observed. The evidence of liver damage was further verified by a significant (p < 0.05) rise in concentrations of hepatic biomarkers viz. Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), and Alkaline phosphatase (ALP). Moreover, ER-stress was validated through the increased intracellular calcium levels along with the heightened expression of grp78, chop, atf4, perk, eIF2α, and gadd34 in exposed groups. This intricate cascade subsequently elicited the activation of bax, caspase-3, caspase-9, and apaf-1, while modulation of bcl-2, thereby driving hepatocyte-apoptosis via ER-stress response in C. punctatus, a widely consumed food-fish. Our findings underscore the toxic threats of Copper-laden PVC-MPs to aquatic life and potentially the broader ecosystem.

Comparative study of immune responses and intestinal microbiota in the gut-liver axis between wild and farmed pike perch (Sander Lucioperca).

Pike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided. In this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch. As a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

12614 Induction Of Gpt2 During Metabolic Stress Is Associated With Reduced Incretin Responsiveness And Decreased β-cell Resilience To Metabolic Stress

Abstract Disclosure: S. Sen: None. A.V. Rozo: None. M. Haemmerle: None. J. Roman: None. A.V. Scota: None. J.A. Christine: None. E.M. Morrow: None. S.A. Tersey: None. C.B. Newgard: None. N.M. Doliba: None. D.A. Stoffers: None. Elevated blood glucose and lipids compromise pancreatic β-cell survival and function, but the underlying molecular mechanisms are ill-understood. We previously found that mitochondrial glutamate-pyruvate transaminase 2 (GPT2) is induced by ER and glucolipotoxic (GLT) stress. Here, we find that islets from type 2 diabetic donors exhibited markedly elevated levels of GPT2 compared to those of non-diabetic donors. GLT stress induced GPT2 in MIN6 cells, primary murine, and human non-diabetic islets. We generated β-cell specific Gpt2-deficient (Gpt2βKO) and Gpt2 floxed control (Gpt2f/f) mice to study the in vivo role of Gpt2 in β-cells. Intraperitoneal (IP) glucose tolerance (GTT) of Gpt2βKO mice was minimally affected on chow diet; therefore, we placed Gpt2f/f and Gpt2βKO mice on 45 kcal% high-fat and matched control diets. At 1 week, HFD-fed Gpt2βKO mice exhibited reduced β-cell death, measured by droplet digital PCR of circulating unmethylated preproinsulin DNA and by TUNEL analysis. Over 37 weeks, HFD-fed Gpt2βKO mice showed lower random blood glucose similar to Gpt2f/f mice under a control diet. While IPGTT was modestly improved in HFD-fed Gpt2βKO compared to HFD-fed Gpt2f/f mice, insulin secretion was not enhanced. Remarkably, oral glucose administration markedly improved glucose tolerance and enhanced insulin secretion of control- and HFD-fed Gpt2βKO mice compared to Gpt2f/f mice, while GLP-1 and GIP levels were unaltered, suggesting enhanced incretin action on the β-cell. Indeed, Gpt2βKO mice (under both control and high-fat diets) were more responsive to administration of GLP1R agonist Exendin-4 (Ex4) than Gpt2f/f mice. Isolated Gpt2βKO islets secreted more insulin when stimulated by Ex4 and GIP but not acetylcholine. Perifusion assay revealed markedly enhanced insulin secretion of Gpt2βKO islets in response to a stepwise exposure to increasing Ex4 doses, indicating enhanced incretin sensitivity. Metabolic flux analysis of Gpt2βKO and Gpt2f/f islets exposed to uniformly labeled glucose (U-13C glucose) under low (2.8mM), high (12mM) glucose, and high glucose with Ex4 conditions revealed elevated levels of key TCA cycle intermediates in Gpt2βKO islets under high glucose and high glucose+Ex4 conditions, indicating increased TCA cycle flux that likely enhances insulin secretion. Gpt2βKO mice had higher β cell mass than Gpt2f/f littermates under control diet and HFD feeding. Bulk islet RNA-seq from Gpt2f/f and Gpt2βKO mice exposed to GLT revealed upregulation of genes responsible for cell cycle and division pathways and downregulation of apoptosis and ER stress genes, consistent with enhanced survival of Gpt2βKO islets under stress conditions. In summary, β-cell GPT2 is increased during metabolic stress and T2D. Its deficiency induces a metabolic reprogramming that improves incretin sensitivity and protects pancreatic β-cells from metabolic stress. Presentation: 6/2/2024