Significant Elevation Of ALT Research Articles

ASSESSMENT OF LABORATORY PARAMETERS IN PATIENTS WITH ACUTE PANCREATITIS OF VARIOUS ETIOLOGIES

Summary. Abstract. Acute pancreatitis remains one of the most prevalent diseases worldwide. Alcoholic and biliary factors are considered the most common causes of AP. The aim of the study was to investigate the laboratory characteristics of patients with AP, taking into account the etiological variant of the disease. Materials and methods: the study is retrospective. Medical records of 677 patients hospitalized for AP in two medical institutions from 2017 to 2022 were analyzed: Vinnytsia сity сlinical emergency hospital and Vinnytsia regional clinical hospital named after M.I. Pyrogov. For further study of laboratory parameters of all AP patients, they were divided into four groups depending on the etiology: alimentary, biliary, alcoholic, and postoperative. The laboratory data obtained within the first 24 hours of hospitalization were analyzed. Results. Intergroup differences in the distribution of laboratory parameters were observed among different etiological variants of AP. Some of them showed only significant intergroup deviations within reference values, while some also deviated from the norm. Specifically, for alimentary AP, there was a significant increase in creatinine levels compared to other groups. For biliary AP, there was a significant increase in leukocyte count, neutrophil-to-lymphocyte ratio, total bilirubin, blood glucose levels, and a significant decrease in lymphocyte count. For postoperative AP, there was a significantly the lowest level of increase of serum amylase levels, significant elevation in ALT and AST levels, and significant increase in stabs neutrophils and ESR compared to other groups. Conclusions. Analysis of blood and urine laboratory parameters in patients with AP allowed to identify intergroup differences in their distribution for different etiological variants of AP without deviation from the norm, as well as deviations from reference values. The obtained data should be taken into account at the stage of hospitalization and the beginning of inpatient treatment of patients with AP for further stratification and development of individualized diagnostic and therapeutic programs.

Protective Effects of Stem Cells and Vitamin D3 Against Hepatic Ischemia/Reperfusion Injury in Rats

Abstract Background Liver transplantation is one of the most efficient life-saving treatments for various end-stage hepatic diseases. However, hepatic ischemic reperfusion injury (IRI) remains a major problem in liver surgeries morbidities and mortalities. Stem cells (SCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine, including liver diseases. Aim to investigate the effect of vitamin D and Bone Marrow Mesenchymal Stem Cells (BM- MSCs) solely or combined on hepatic IR injury. Methods Sixty adult male Wister rats were allocated into 5 groups; Sham, IR: underwent hepatic IR, vit. D-IR: received vit. D in a dose of 500 IU/Kg/day, by gavage, 5 days/week for 2 weeks, then subjected to hepatic IR, Stem cell-IR: received single IV injection of 1 × 106 BM-MSCs prior to hepatic IR and Combined-IR: received both vit. D and BM-MSCs prior to hepatic IR. All rats were subjected to estimation of Liver index (LI), assessment of serum levels of alanine, aspartate transaminases (ALT, AST) and vitamin D, hepatic tissue levels of Malondialdehyde (H.MDA), Superoxide dismutase (H.SOD), Interleukin-2, 10 (H.IL-2, H.IL-10), Caspase-3 (H.Casp-3), H.LC3B and hepatocyte growth factor (H.HGF), as well as histopathological liver examination and scoring. Results Hepatic IR resulted in significant elevation of ALT, AST and H.MDA, H.IL-2, H. Casp- 3 as well as significant reduction in LI, vit. D, H.SOD, H.IL-10, H.LC3B and H.HGF with evident hepatic sinusoidal congestion, cytoplasmic vacuolation and cellular necrosis. Treatment either solely or in combination mitigate these changes with the combined treatment showed the best results compared to the individual use. Conclusion In vivo coadministration of vitamin D and BM-MSCs prior to hepatic IR attenuated hepatocellular damage through preventing oxidative stress and inflammatory response, augmenting autophagic, regenerative capacity and anti-apoptotic effect.

Effects of Desflurane exposure and Laparotomy on genomic biomarkers and hepatic histopathology in an experimentally induced liver injury model: A pilot study

Background Halogenated anesthetics are known to cause hepatotoxicity that can be evaluated by the emerging genomic biomarkers, that is, miRNA-122 and miRNA-192. Methods Thirty Wister rats were distributed randomly in five equal groups; Control Group (group C); Desflurane Group (group D); Hypoxia Group (group H); Hypoxia + Desflurane Group (group HD); and Hypoxia + Desflurane + Laparotomy Group (group HDL). Animals in the Groups D, HD, HDL were exposed to 6% desflurane. Rats were exposed to hypoxic mixture in Groups H, HD, and HDL. Animals in Group HDL were additionally subjected to laparotomy with liver palpation. After 24 hours, plasma ALT, AST, GGT, blood and tissue miR-122, and miR-192 gene expression and histopathological examination of liver biopsies were performed. Results Plasma and tissue miR122 and miR192 showed significant increase ascendingly in H, D, HD, HDL groups (p value <0.05), significant elevation of ALT, AST, GGT in HD and HDL groups (p value <0.05). Hepatic histopathological findings revealed 33.3% inflammatory infiltration in group D, 50% in group H, 66.6% in HD and HDL groups. 16.7% apoptosis was detected in D & H groups and 33.3% in HD and HDL groups, while none showed necrosis. Conclusion This experimental study concluded that each desflurane and hypoxia has deleterious effect on hepatic integrity, which increased by their combination and aggravated by surgical influence as verified by miR-122 and miR-192, as well as histopathological examination. Assessment of hepatotoxic effects of other various anesthetics and different surgical approaches in experimental study using hepatic genomic biomarkers is recommended.

Hepatic ROS Mediated Macrophage Activation Is Responsible for Irinotecan Induced Liver Injury

Irinotecan is the first line chemotherapy drug used for treatment of metastatic colorectal cancer worldwide. There is increasing evidence suggesting that liver damage, including steatosis and steatohepatitis, can be caused during the treatment involving irinotecan. However, molecular mechanisms by which irinotecan-induced liver injury remain elusive. In this study, we found that irinotecan treatment caused significant elevation of ALT, inflammation, and fat accumulation in the liver, which are associated with hepatic macrophage activation. Depletion of macrophages by clodronate liposome improved irinotecan induced liver injury and inflammatory response in mice. In vitro data indicated that irinotecan induced intracellular ROS production in primary hepatocyte and upregulating of toll-like receptor (TLRs) family expression in macrophages. Supernatant from irinotecan treated hepatocyte triggered macrophage activation and upregulation of TLRs in macrophage, and N-acetylcysteine (NAC) abolished these effects. By using co-culture system, we further revealed that irinotecan activated macrophage induced impairment of lipid metabolism and promoted apoptosis in hepatocyte and NAC prevented macrophage-induced cell death and partially revered impaired lipid metabolism in hepatocytes. By using the irinotecan liver injury model, we demonstrated that combining NAC with irinotecan prevented irinotecan-induced macrophage activation, TLR upregulation, liver injury, and partially prevented the accumulation of triglycerides in liver. Our results thus indicated that macrophages play a critical role in irinotecan-induced liver injury, and targeting ROS provides new options for development of hepatoprotective drugs in clinical practice.

Phycocyanin improved alcohol-induced hepatorenal toxicity and behavior impairment in Wistar rats

The aim of this study was to investigate a potential preventive effect of phycocyanin extract from Spirulina platensis against ethanol- induced hepatorenal toxicity and cognitive behavior impairment in male Wistar rats. The animals were randomly and equally divided into four groups (six animals each): control group received saline solution, ethanol (EtOH) group was injected intraperitoneally with 1 ml/kg of ethanol solution 38% (w/v), phycocyanin groups were treated with 25 (PC1) or 50 (PC2) mg/kg phycocyanin extract followed by ethanol administration. All treatments were conducted for 14 successive days. Results revealed that ethanol induced oxidative stress in brain, liver, and kidney by increasing lipid peroxidation level and SOD and CAT activities. Serum biochemical perturbations were also observed in EtOH group, which was indicated by a significant elevation in ALT, AST, cholesterol, triglycerides, creatinine, and urea levels. Combined exposure to EtOH with phytocyanin contracted these biochemical alterations. Phycocyanin decreased also EtOH-induced anxiety and ameliorated exploratory behavior assessed by the elevated-plus maze and open field tests respectively.

Deciphering the Significance of Plasma Chemokines as Prognostic Biomarkers in Pegylated IFN-Α-2a /Ribavirin-Treated Chronic Hepatitis C Genotype 4 Patients.

Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective. Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy. Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA). A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy. Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma. Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFβ / p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity

Chronic liver disease is a worldwide health problem. Carbon tetra hydrochloride is an environmental toxin which is regarded as highly toxic and a potential human carcinogen. It can cause liver damage through the generation of metabolites and production of free radicals. Green tea contains catechins such as Epigallocatechin gallate which has been found to reduce the inflammation, oxidative stress, and fibrosis in experimental animal models. Hence, it represents a good source to prevent or ameliorate several chronic diseases. Silymarin is extracted from milk thistle seeds and has been found to be an effective agent to reduce the oxidative stress and free radical production and thereby exert protective effects in chronic liver conditions. The present study was planned to keep in view the above-mentioned facts. We included thirty rats in our study and divided them into five groups, each having six rats and the study continued for 8 weeks. Group I received normal saline; Group 2 received i.p. CCl4 injections; Group 3 received CCl4 i.p. injection and Epigallocatechin gallate (EGCG) oral gavage, Group 4 received CCl4 i.p. injection and silymarin by oral gavage; and Group 5 received CCl4 i.p. injection and combined EGCG + silymarin by oral gavage. The study found that in group 2, CCl4 induced significant elevation of ALT and MDA and reduced GSH thereby signifying increased oxidative stress. CCl4 also significantly increased inflammatory (TNFα, NFκB, IL1β, and TGFβ) as well as fibrotic markers (p-ERK and p-Smad1/2 protein expression). EGCG and silymarin significantly reversed the previously mentioned parameters either alone or in combination; however, the effect was more pronounced in case of EGCG. We conclude that EGCG and silymarin possess liver protective effects through their antioxidant, anti-inflammatory, and antifibrotic action.

Effect of l-carnitine supplementation on lead acetate-induced liver cell apoptosis and inflammation: role of caspase-3 and glycogen synthase kinase-3β enzymes

AimThe study aimed at studying the hepatoprotective effect of l-carnitine against lead (Pb) acetate-induced hepatocellular injury, emphasizing the role of caspase-3 and glycogen synthase kinase-3β in hepatocellular apoptosis and inflammation. Materials and methodsMale Wistar rats were used. The experimental approach involved estimation of the liver enzymes' serum levels. Oxidative and inflammatory biomarkers were measured in hepatic tissue homogenates. Paraffin-embedded hepatic sections were prepared for histopathology and immunohistochemistry. Quantitative determination of the phosphorylated glycogen synthase kinase-3 beta was performed. Key findingsThe serum showed a significant elevation in ALT, AST, and LDH; tissue homogenates showed significant elevation in lipid peroxide and inflammatory biomarkers with significant reduction in reduced glutathione in the Pb acetate-treated group. Co-administration of l-carnitine with Pb acetate produced significant reduction in liver enzymes with significant improvement in oxidant, antioxidant and inflammatory markers. Lead acetate treatment significantly reduced the phosphorylated glycogen synthase kinase-3 beta, while l-carnitine enhanced its phosphorylation. Histopathological examination showed inflammatory reaction around blood vessels with fatty degeneration in hepatocytes of the Pb acetate intoxicated group. l-Carnitine caused a decrease in hepatic damage with minimal vascular alterations in central vein. Caspase-3 expression in hepatocytes was decreased in Pb-treated group supplemented with l-carnitine. SignificanceOur study reveals that oxidative stress and inflammation participate in Pb acetate-induced hepatocellular injury. Glycogen synthase kinase-3β and caspase-3 play role in Pb acetate-induced hepatic damage. l-Carnitine shows significant protective effects against hepatocellular apoptosis and inflammation induced by Pb acetate through antioxidant, anti-inflammatory and anti-apoptotic pathways in part mediated by GSK-3β inhibition.

Liver protection from acetaminophen hepatotoxicity using copper(I)-nicotinic acid complex

The present study was performed to investigate the hepatotoxicity of acetaminophen and the possible hepatoprotective effect of copper(I)-nicotinate in rats through biochemical light and electron microscopy studies. Two groups of rats (39 in total) were used: group I (15 rats) received acetaminophen by intraperitoneal injection in a dose of 1000 mg/kg. While group II (15 rats) received an oral dose of 800 μg/kg copper(I)-nicotinate dissolved in 0.5 mL of saline three times through 24 h and 1 h after the last dose, and 9 rats were kept as control. Blood and tissue samples for biochemical, light, and electron microscopy were collected after 4, 12, and 24 h. Biochemical results showed a significant elevation in ALT, AST, and nitric oxide levels in rats who received acetaminophen only. In contrast, the corresponding levels of treated rats with the copper complex showed a less significant elevation in ALT, AST, and nitric oxide. Light microscopic examination of liver tissue taken from intoxicated animals showed congestion of the vasculature with hydropic and fatty degeneration. Centrilobular necrosis of the hepatocytes with glycogen depletion was observed in the centrilobular areas. Ultrastructural examination showed fatty degeneration, mitochondrial swelling, severe irregular dilatation of RER and SER, loss of glycogen granules, and pyknosis of the nuclei. Examination of livers of animals that received copper complex before intoxication revealed only cup-shaped mitochondria, a mild degree of fatty degeneration, and glycogen depletion with no evidence of necrosis. This work provides evidence for the antioxidant properties of the copper(I)-nicotinate complex and illustrates the pathological changes induced by acetaminophen in liver tissue.

A Cross-Species Transmission of a Camel-Derived Genotype 8 Hepatitis E Virus to Rabbits.

Novel genotypes of hepatitis E virus (HEV), i.e., HEV-5, HEV-7, and HEV-8, have been identified in wild boar, dromedary camels, and Bactrian camels, respectively, and they transmit to cynomolgus monkeys in a trans-species manner, raising the potential for zoonotic infection. Rabbits are the natural reservoir for rabbit HEV, but they are also susceptible to HEV-3 and HEV-4. It has been unknown whether rabbits are susceptible to HEV-5, HEV-7, and HEV-8. To investigate the infectivity of novel HEVs in rabbits and to assess whether rabbits are appropriate animal models for these HEVs, we inoculated Japanese white rabbits with HEV-5, HEV-7, and HEV-8, respectively. We observed that viral RNA was present in the fecal specimens of the HEV-8-inoculated rabbits and anti-HEV IgG antibodies were present in its sera, although anti-HEV IgM was undetectable and no significant elevation of ALT was observed. These results indicated that HEV-8 crossed species and infected the rabbits. No evidence for replication was observed in HEV-5 and HEV-7, suggesting that rabbits are not susceptible to these genotypes. The antibodies elicited in the HEV-8-infected rabbits did not protect them from the rabbit HEV challenge, suggesting that the antigenicity differs between HEV-8 and rabbit HEV. Antigenic analyses demonstrated that anti-HEV-8 antibodies reacted more strongly with homologous HEV-8 virus-like particles (VLPs) compared to heterologous rabbit HEV VLPs, but anti-rabbit HEV antibody had similar reactivity to the VLPs of rabbit HEV and HEV-8, suggesting that HEV-8 lacks some epitope(s) that exist in rabbit HEV and induced the neutralizing antibodies against rabbit HEV.

Estimate Toxic Effect Of Silica Nanoparticles On Kidney, Liver And Lung Function Of Male Albino Rats

The current study was carried out in the animal house of faculty of science/Kufa university on thirty male albino rats to determine the toxic effect of nano silica on some organs, kidney, lungs and liver in the male adult rats that treated with two concentrations (100,150)mg/kg of silica nanoparticles for 30 days. the kidney and liver functions were determined by biochemical markers (AST, ALT, Urea and Creatinine), and histopathological analysis was performed to all studied organs .the results showed a significant elevation in ALT, AST Urea and Creatinine levels in serum of male rats .the histopathological results showed severe damage in the tissue of kidney, liver and lungs especially at high concentration 150mg/kg. It caused necrosis, dilation in renal tubules and inflammation of hepatocytes, also, there was metaplasia in mucous and hypertrophy in lung tissue, these findings as a response to administration orally of silica nanoparticles.

RELATION OF LACTOBACILLI ACIDOPHILUS TO NON-ALCOHOLIC FATTY LIVER IN A SAMPLE OF EGYPTIAN POPULATION

Background: Non-alcoholic fatty liver disease (NAFLD) is an insidious disease, which leads to the deposition of lipid within the hepatic parenchyma. It affects different age groups in Egypt—including children. Its degree of severity range from steatosis to non-alcoholic steatohepatitis (NASH), which later could progress into life-threatening diseases such as cirrhosis and hepatic malignancy. Progression towards inflammation of the steatotic liver was initially proposed to be related to endotoxemia as a result of increased gut permeability. Subsequently, there is some evidence that intestinal microbiota plays an important part in the pathogenesis of NAFLD.Aim of the work: To detect possible relation of lactobacillus acidophilus to non-alcoholic fatty liver disease in a sample of Egyptian population.Patients and methods: The current study included 60 subjects. They were divided in to Group 1: included 20 obese subjects with NAFLD; Group 2 :included 20 lean subjects with NAFLD; Group 3: included 20 healthy subjects as a control group. Identification of stool lactobacillus acidophilus by quantitative real time PCR technique and abdominal ultrasound for diagnosis of NAFLD.Results: There was non significant difference between studied groups as regard lactobacillus acidophilus concentration in stool P= 0.986. There was non significant elevation of ALT and AST in NAFLD obese subjects in positive PCR group compared to other groupsConclusions: Still there is controversy about the role of lactobacillus acidophilus in the pathogenesis of NAFLD

Impact of liver enzymes on SARSCoV-2 infection and on the severity of clinical disease

Background and aim: SARSCov-2 infection, currently responsible virus for the pandemic, can have a multi-organic impact, recent studies show that liver injury could be a manifestation of the disease, and liver disease could also be related to a worst prognosis. AIM: To compare the characteristics of patients with severe COVID-19 due to SARSCov-2 disease requiring intubation versus stable patients. Methods. Type of Study: Observational, a case-control, nested in a cohort study. Procedure: Complete medical records of patients admitted for COVID-19 at a third level center were reviewed. Clinical and biochemical data were collected and then characteristics between seriously ill patients who required intubation were compared versus stable patients without mechanical ventilation. Result(s): We included 166 patients with COVID-19 due to SARSCov-2 infection, 114(68.7%) were men, mean age was 50.6 +/- 13.3 years old, 27(16.3%) were assessed as seriously ill patients requiring intubation for SARS. The comparative analysis between those who required intubation versus those who remained without requiring intubation showed significant elevation of ALT, AST, LDH and D-dimer, also older age, see Table. Conclusion(s): This is the first study in a Mexican cohort, which demonstrate that seriously ill patients have significant raises of liver enzymes (AST, ALT) with prognostic implications in the SARSCov-2 disease course. Conflicts of interest: The authors have no conflicts of interest to declare.Copyright © 2020

Investigation on the effects of copper deficiency on fertility and some hematobiochemical parameters in rams with trial for treatment

Fecal samples and blood samples were collected from 80 rams (50 suffering from unthriftness, weakness, diarrhea, recumbency of some rams - 30 from healthy ram) from private farms at Abo Hamad city, Sharkia Province for parasitological examination and estimation of copper level in blood. Post parasitological examination 15 rams were divided into three equal groups. 1st Gp healthy rams free from any parasites with normal copper level (control), 2nd Gp rams suffering from previous signs with low copper level not treated, 3rd Gp rams suffering from previous signs with low copper level treated with 1gm copper sulphate /liter drinking water for one month. At 1st, 15th and 30th day post treatment blood and semen samples were collected from each ram for study hematobiochemical parameters and semen character. Parasitological examination of faecal samples revealed presence of parasites eggs in 11 healthy rams (6 single infection - 5 mixed infection) beside presence parasites eggs in 20 hypocuprotic rams (11 single infection - 9 mixed infection) Hypocupritic rams revealed significant decrease in RBCs, Hb, PCV, WBCs, total protein, albumin, globulin, copper, selenium, zinc, iron, testosterone, triiodothyronine, thyroxin, sperm number, sperm motility, insignificant reduction in ejaculate volume, significant elevation in ALT, AST, ALP, urea, creatinine, dead sperm and sperm abnormality. Improvement of hematobiochemical and semen parameters was observed at 1st day post treatment with copper sulphate. It could be concluded that copper deficiency affects male fertility and hematobiochemical parameters, copper sulphate is effective in ameliorating adverse effect of copper deficiency in rams.

Parameters of Metabolic Syndrome in Obese Children and Adolescents.

Abstract Background: Obesity is the most common chronic metabolic disease in children and adolescents. It has reached epidemic ranges and is a significant global problem. Objective: This study aimed to investigate the possible metabolic disturbances in children and adolescents with obesity and severe obesity. Subjects and methods: This cross-sectional study included 158 (82 boys, 76 girls) obese children and adolescents between ages of 0 and 17years (10.43 ± 3.11 years). The obesity was defined according to the sex- and age-specific growth charts proposed by the Centers for Disease Control and Prevention as BMI ≥ 95th percentile. Severe obesity was classified as 120% of the 95th percentile for age and sex. Study participants underwent medical assessment and analysis of: ALT, AST, fasting serum triglycerides, total serum cholesterol, fasting plasma glucose and plasma glucose from oral glucose tolerance test. Results: The majority of study participants were severely obese (69.92%). The highest distribution of abnormal biochemical results was seen in elevated ALT (53.91%) followed by elevated triglycerides (34.75%). The prevalence of abnormal total cholesterol level was significantly higher (p=0.04) in the group of obese children compared to the severely obese children. The levels of total cholesterol were also statistically higher in the group of adolescents compared to preadolescents (p=0.02). An important number of obese patients (2.5%) and even higher number of severely obese patients (5.26%) had carbohydrate intolerance. Conclusion: There was a significant elevation of ALT, total serum cholesterol and triglycerides in all study participants. High serum lipids and high hepatic enzymes (as introduction in non-alcoholic fatty liver disease) are alarming. Strikingly, there was carbohydrate intolerance in an important number of patients. Treatment and education of patients and parents is mandatory. Preventive measures in the society concerning childhood obesity are necessary.

Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide

BackgroundCyclophosphamide (CP) is an anticancer drug utilized for treatment of many types of cancer. CP causes many side effects such as hepatotoxicity and mutagenicity. Garlic has long been used as a spice and food additive and is considered as one of the important medicinal plants. Garlic had medicinal importance as it has hepatoprotective, antimicrobial, antioxidant, anti-inflammatory, antithrombotic, antihypertensive, and antihyperlipidemic properties. The purpose of the presented study is to investigate the protective role of aged black garlic against cyclophosphamide-induced hepatotoxicity and apoptosis. The present work was carried out by routine histological H&E stain, histochemical Feulgen stain for DNA, immunohistochemical stain Bcl-2 as apoptotic marker, comet assay, serum biochemical analysis for liver function markers (ALT, AST, albumin, and bilirubin), and hepatic oxidative stress markers (MDA, CAT, SOD, and GPx).ResultsCyclophosphamide induced histological alteration as fatty degeneration, blood venous congestion, pyknosis, necrosis, and vaculations. CP caused a decrease of DNA content, an increase of Bcl-2 immunoreactivity, and increase of DNA damage. Biochemical investigations showed that CP induced significant elevation of ALT, AST, bilirubin, and hepatic MDA. Moreover, CP induced reduction of albumin and hepatic SOD, CAT, and GPx values. Aged black garlic induced significant improvement of alterations induced by CP, when compared with CP-treated group.ConclusionAged black garlic succeeded in protecting the liver from apoptosis and pathological alterations induced by CP.

GENETIC SUSCEPTIBILITY AND HEALTH EFFECTS OF OCCUPATIONAL EXPOSURE TO NITROAROMATIC COMPOUNDS IN AMMUNITION INDUSTRY (B)

Introduction: In factory workers, exposure to nitroaromatic compounds has been linked to many adverse health effects. Aim of work: To study the role of polymorphisms of Glutathione S-transferase ( GST) gene as an effect modifier in relation to nitroaromatic induced health hazards. Materials and methods: The study was conducted on 40 workers as an exposed group comprising all workers engaged in ammunition production in a military factory in Helwan area, and a control group of 40 workers. All participants were subjected to an occupational and medical history questionnaire with full clinical examination, slit lamp examination, ECG scanning and laboratory investigations that included: liver and kidney functions, complete blood picture and serum 8-OHdG. Genetic study of GST gene polymorphism was done for the whole population. Multiplex PCR was performed for determination of GSTM1 and GSTT1 genes polymorphisms in the isolated DNAs, while PCR –Restriction Fragment Length Polymorphism (PCR- RFLP) was performed for GSTP1 gene polymorphisms. Results: Regarding frequency distribution of GST genes, in the exposed workers, intact gene of GST (M, T) and the wild GST (P) genes were more prevalent (57.5%, 65% and 62.5% respectively). However, in the control group, the intact gene of GST (M) and the wild GST (P) genes were more prevalent (95% and 77.5% respectively). In the exposed group regarding GST genes polymorphism, null GSTM gene group were predisposed to flushing, lower levels of Hematocrit value and Hb levels and blood urea. GSTP mutation group showed highly significant elevation of ALT and AST levels compared with intact gene group, while significant higher prevalence of ischemic heart diseases and level of Introduction Nitroaromatic compounds have been reported as toxic, mutagenic and carcinogenic. They are used in multiple applications as pharmaceuticals, antimicrobial agents, food additives, pesticides, explosives, dyes and raw materials in several industrial processes (Oliveira et al., 2010).TNT is one of the most recalcitrant and toxic of all the military explosives used (Padda et al., 2003). It is used in military shells, bombs, and grenades, in industrial uses, and in underwater blasting (Oliveira et al., 2010). TNT has accumulated in areas of manufacturing, storage, and decommissioning over recent decades. Various government agencies, such as the EPA have listed TNT as a priority pollutant and have recommended that it should be removed from contaminated sites to prevent environmental and health problems (Van Aken, 2009).Despite the strong causal associations between certain occupational exposures and related health hazards, still there are differences in disease incidence between workers that cannot be accounted for by differences in exposures or work practices. Genetic polymorphisms account for some of these differences, thus should be included as relevant variables in study design and analysis (NIOSH, 2004).Glutathione S-transferase (GST) enzymes comprise a family of phase II detoxifying metabolic enzymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates (Atkinson and Babbitt, 2009), thus preventing their interaction with crucial cellular proteins and nucleic acids (Hayes et al., 2005 and Josephy, 2010). It is an important detoxifying mechanism ensuring more soluble substrates and allowing them toALT in GSTT null gene carriers on the other hand a significant higher mean level of creatinine and lower mean level of AST, was noted among exposed workers with GSTT nun null gene carriers. Conclusion: Genetic polymorphism in members of the GST gene family may be considered as an effect modifier and as genetic susceptibility for some nitroaromatic compounds health hazards. Recommendations: Further studies are recommended on a larger scale to study the net effect of multiple contributing genes.

Biochemical abnormalities in OPC poisoning and its prognostic significance

BACKGROUND: Organophosphorus insecticides are arguably one of the commonest causes of morbidity and mortality due to poisoning worldwide, especially in developing countries like India due to its easy availability. Though Serum cholinesterase can be a useful tool in the diagnosis of OP poisoning, its role in prognostication is very minimal. Our study was conducted to other biochemical abnormalities to predict the severity and prognosis in OP poisoning patients. AIMS AND OBJECTIVES: (1)To measure serum electrolytes, liver enzymes, amylase, CPK, CPK-MB, and Troponin I in acute organophosphorus poisoning (2) To analyse the correlation between these biochemical parameters and serum acetylcholinesterase levels (3) To analyse the validity of these biochemical parameters in prediction of severity and prognosis in op poisoning. MATERIALS AND METHODS:This study was conducted over a period of 1 year in Mahatma Gandhi Memorial Government Hospital attached to K.A.P.V Govt Medical College, Trichy wherein 50 OP poisoning patients were selected using inclusion and exclusion criteria and their blood samples were collected on admission and analysed for the above said biochemical parameters. RESULTS: 74% of the patients were male, and 62% of the patients fall in the age group of 20 to 30 years. Statistically significant elevation of ALT, CPK, CPK-MB and Troponin I were noted in the study group. A significant fall in serum potassium level in also noted. Most of the patients in the study had a cholinesterase level of 20% to 50%. CONCLUSION: AST, ALT, ALP, and Amylase increase in acute OP poisoning. Rise in CPK, CPK-MB, Troponin I and ALT indicate the severity of OP poisoning and is also statistically significant to predict the prognosis of the patient. Hypokalaemia and associated low cholinesterase levels indicate the requirement of ventilator support and also the poor prognosis of the patient. These findings can assist health professionals to better evaluate patient’s prognosis and improve their treatment plan.

Nonionic surfactant based thymoquinone loaded nanoproniosomal formulation: in vitro physicochemical evaluation and in vivo hepatoprotective efficacy

Context: The present study was carried out to formulate thymoquinone proniosomal formulation (TQP) and evaluate their efficacy in methotrexate (Mtx) induced hepatotoxicity in rats.Objective: The objective of the study was to explore a new therapeutic approach focusing on hepatoprotective activity using thymoquinone proniosomal formulation.Material and methods: TQP was formulated using span60, cholesterol and phospholipid by film hydration technique. The animals were divided into six groups with five animals each receiving different treatments for 7 days. On the 8th day, rats were anesthetized with ether, blood samples were withdrawn, livers were dissected out for biochemical tests and histopathological examinations.Results and discussion: The size of vesicle was found to be in the nanometric range with higher entrapment efficiency. The high entrapment efficiency is probably due to the lipophilic character of TQ. The morphological structure showed the outline and core of the well-identified spherical vesicle, and also displaying the retention of sealed vesicular structure. The release of TQ from developed formulation was found to be significantly higher compared to control. Mtx treated rats showed significant elevation in ALT, AST, ALP and TBARs, whereas, TQP treated group showed significant reduction.Conclusion: The developed formulation (TQP) significantly inhibited the elevated levels of serum marker enzymes and showed improved histopathological deformities.

Protecting Role of Selenium on the Cytotoxic Effect of Profenofos on Rabbit Fertility

Profenofos is an Organophosphorous compound and acaricide used in Egypt with cumulative toxic effects causing reproductive dysfunction and increase in reactive oxygen species production. Protective and anti-oxidant effects of selenium can improve the activity of radical scavenger. So, the aim of this study was to elucidate the protective effects of Selenium against reproductive toxicity induced by Profenofos in male and female New Zealand rabbits (n=18). Three experimental groups (3 males and 3 females per each group) receiving a combination of Profenofos (70 mg/ kg b. w.) and/or selenium in drinking water (25 mg/ kg b. w.) for 90-day was divided as follows: non treated (control), Profenofos alone and Profenofos + selenium group. Profenofos caused a decrease in body and organs weights compared to control group. It had a fetotoxic effect resulting in a significant reduction in pregnancy rate and the number of viable feti in treated animals. Also, Profenofos caused a significant elevation in ALT, AST, MDA, urea and creatinine, while a significant decrease was noticed in SOD, GSH, testosterone, estrogen and progesterone in all treated rabbits compared to control group. Concomitant administration of selenium with Profenofos alleviated the induced alterations. In addition to, histopathological results revealed that testes, epididymis, ovary and uterus alterations represented by degenerative and inflammatory changes as a result of Profenofos exposure. Profenofos had a carcinogenic effect on uterus as leiomyoma with rhabdomyosarcoma which gave positive immunoreactivity with Desmin and Smooth muscle actin. Also, Profenofos caused histopathological and histochemical effects in liver and kidney tissues. There was intensive positive immunoreactivity for caspase- 3 (dark brown granules) was observed in the cytoplasm of apoptotic testicular, ovarian and uterine cells that indicating the severity of Profenofos toxicity. On the other hand, examined tissues of Profenofos in combination with selenium treated group showed apparent reduction of caspase-3 immunoreactivity to be more or less similar to the control group. In conclusion, selenium is a valuable cytoprotective which reduced the oxidative stress toxicity induced by Profenofos in the reproductive system of male and female as well as liver and kidney albino rabbits.