Links between Inflammation and Insulin Resistance in Children with Morbid Obesity and Metabolic Syndrome

Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Effect of the Ethanolic Leaf Extract of Ficus exasperata on Biochemical Indices of Albino Mice Experimentally Infected with Plasmodium berghei (NK 65)

Ficus exasperata is a plant used in the traditional management of malaria in south-south Nigeria. An investigation into the effects of the ethanolic extract of the leaf of the plant on some biochemical indices in albino mice infected with Plasmodium berghei (NK 65) was conducted. 48 mice with weight range of 13-23 g were grouped into six (A, B, C, D, E, and F). Each group contained 8 mice. Groups A, B, C, D and E were infected with blood containing the parasite. Group F was not infected and served as the normal control. On the 6th day after infection, 4 mice from each group were sacrificed and blood samples are collected for investigation. The remaining mice in each group were treated. Mice in Groups A, B and C were administered orally with 200, 300 and 500 mg/kg body weight of Ficus exasperata respectively for six days. Group D was not treated while Group F was given distilled water. Group E was treated with 5 mg/kg body weight of chloroquine. On the 6th day post treatment, these mice were sacrificed and blood samples were collected for biochemical analysis. The results indicated that on the 6th day post inoculation, the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) in all the mice infected with the parasite were significantly (p < 0.05) elevated. However, on the 6th day post administration of extract, the increased levels of AST, ALP and ALT were significantly (p < 0.05) reduced in groups administered with 300 and 500 mg/kg body weight of the extract compared with groups D and F. The reduction in the levels of these enzymes is an indication that F. exasperata have no hepatotoxic effect on the mice at the dose levels administered.

Toxicological and Histopathological Studies on the Effect of Tartrazine in Male Albino Rats

Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD50) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Assessment of Diagnostic Enzymes as Indices of Heavy Metal Pollution in Tilapia Fish

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65mg/l of Pb, 0.85mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Influence of Pomegranate (Punica granatum L.) on Dimethoate Induced Hepatotoxicity in Rats

Pomegranate (Punica granatum L.) is an ancient fruit of great medical interest and rich source of antioxidants. Pesticides as dimethoate play a crucial role in the occurrence many diseases in plants, animal and human. Therefore the ability of Pomegranate (Punica granatum L.) to alleviate hepatotoxicity induced by organophosphate pesticide dimethoate was investigated. Albino male rats were divided randomly into 4 groups and kept at 7 animals per group in an environmentally controlled condition for 6 weeks. The first group was served as a control group (basal diet), the second group fed on basal diet supplemented with 5% freeze dried pomegranate seeds, the third group fed on 20 ppm dimethoate contaminated diet and the last group fed on dimethoate contaminated diet supplemented with 5% freeze dried pomegranate seeds. The results revealed that administration of dimethoate caused high significant increased in liver functions: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities as well as lipid peroxide (malonaldhyde, MDA); on the other hand high significant decreased on glutathione (GSH), glutathione peroxidase (GPx), albumin and total protein were observed. However addition of 5% freeze dried pomegranate seeds significantly improved all previously mentioned parameters. These results indicate the dimethoate induced hepatotoxicity and highlight the protective effect of pomegranate seeds as a potential protective agent against dimethoate induced hepatotoxicity. This may be attributed to the powerful antioxidants (polyphenols, total phenols, and total flavonoids) which present in high levels in pomegranate as well as improving the immunity by activation of antioxidant enzymes GSH and GPx.

Cannabidiol Treatment Ameliorates Acetaminophen-Induced Hepatotoxicity in Mice

The possible therapeutic effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against acute hepatotoxicity induced by a single oral dose of acetaminophen (500mg/kg) in mice. Cannabidiol (two intraperitoneal injections, 5mg/kg, each) was given 1 hour and 12 hours following acetaminophen administration. Acetaminophen administration caused significant elevations of serum alanine aminotransferase, and hepatic malondialdehyde, and nitric oxide levels, and a significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters resulted from acetaminophen administration. Also, histopathological examination showed that cannabidiol markedly attenuated ameliorated acetaminophen-induced liver tissue damage. These results emphasize that cannabidiol represents a potential therapeutic option to protect against acetaminophen hepartotoxicity which is a common clinical problem.

Effect of Oral Administration of “Gadagi“ Tea on Liver Function in Rats

Effect of oral administration of “Gadagi" tea on liver function was assessed on 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg, 315mg/kg for “sak", “sada" and “magani" respectively), standard dose ( 760mg/kg, 830mg/kg, 730mg/kg for “sak-, “sada" and “magani" respectively) and high dose (1500mg/kg, 1700mg/kg and 1460mg/kg for “sak--,"sada" and “magani" groups respectively) for a period of four weeks. Animals that were not administered with the tea constituted the control group. At the end of fourth week, the animals were sacrificed and their serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and globulins (GLO) were determined. Mean serum ALT and ALP activities were significantly higher (P

Protein Profiling in Alanine Aminotransferase Induced Patient cohort using Acetaminophen

Sensitive and predictive DILI (Drug Induced Liver Injury) biomarkers are needed in drug R&D to improve early detection of hepatotoxicity. The discovery of DILI biomarkers that demonstrate the predictive power to identify individuals at risk to DILI would represent a major advance in the development of personalized healthcare approaches. In this healthy volunteer acetaminophen study (4g/day for 7 days, with 3 monitored nontreatment days before and 4 after), 450 serum samples from 32 subjects were analyzed using protein profiling by antibody suspension bead arrays. Multiparallel protein profiles were generated using a DILI target protein array with 300 antibodies, where the antibodies were selected based on previous literature findings of putative DILI biomarkers and a screening process using pre dose samples from the same cohort. Of the 32 subjects, 16 were found to develop an elevated ALT value (2Xbaseline, responders). Using the plasma profiling approach together with multivariate statistical analysis some novel findings linked to lipid metabolism were found and more important, endogenous protein profiles in baseline samples (prior to treatment) with predictive power for ALT elevations were identified.

Evaluation of Some Prominent Biomarkers in Rural Type – 2 Diabetes Mellitus Cases in Kanyakumari District, Tamil Nadu, India

Life is beautiful. But, it is decided by genes, environment and the individual and shattered by the natural and / or the invited problems. Most of the global rural helpless masses are struggling for their survival since; they are neglected in all aspects of life including health. Amidst a countless number of miserable diseases in man, diabetes is becoming a dreaded killer and ramifying the entire globe in a jet speed. Diabetes control continues as a Herculean task to the scientific community and the modern society in the 21st century also. T2DM is not pertaining to any age and it can develop even during the childhood. This multifactorial disease abruptly changes the activities of certain vital biomarkers in the present rural T2DM cases. A remarkable variation in the levels of biomarkers like AST, ALT, GGT, ALP, LDH, HbA1C, C- peptide, fasting sugar, post-prandial sugar, sodium, potassium, BUN, creatinine and insulin show the rampant nature of T2DM in this physically active rural agrarian community.