HEPATOPROTECTIVE EFFECT AND ANTIOXIDANT CAPACITY OF NARINGENIN ON ARSENIC-INDUCED LIVER INJURY IN RATS

Objective: The present study was undertaken to evaluate the protective effect of naringenin (Ng) against arsenic (As)-induced oxidative stress in the liver of experimental rats. Arsenic is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties.Methods: Forty male rats were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with naringenin (50 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and naringen.Results: Exposure of rats to (As) caused a significant increase in liver MDA level compared to control, but the coadministration of (Ng) was effective in reducing its level. The enzymatic activities of glutathione peroxidase (GPx), and glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase(CAT)of As-treated group were found to be lower compared to the control and the (Ng)-treated group. On the other hand, a significant increase in activities of AST, ALT and ALP were observed in As-treated group. The co-administration of (Ng) has decreased the activities of AST, ALT and ALP and thus co-administration of (Ng) had an additive protective effect on liver enzyme activities and improved the antioxidant status as well.Conclusion: To conclude, the results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the (Ng) co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.Keywords: Arsenic, Naringenin, Oxidative stress, Hepatic activit

Different chemical behaviors and antioxidant activity of three novel schiff bases containing hydroxyl groups. X-ray structure of CH2{cyclo-C6H10-NH=CH-(2-O-naphth)}2.H2O

The antioxidant activities of three new Schiff base compounds, 1–3, were studied through their direct scavenging ability to eliminate free radicals using DPPH and ABTS methods and also through their indirect antioxidant activity as measured using the ferric thiocyanate (FTC) method. The number of OH groups in the compounds and their positions play a role in the activity. The crystal structure of CH2{cycloC6H10NHCH-(2-O-naphth)}2.H2O (1), has been determined and proves the existence of intramolecular hydrogen-bonds and hydrogen-bonded water molecules and reveals the keto-amine (NH⋯O) tautomer of this compound. One cyclo-hexyl ring was found to be disordered, and was resolved in two orientations. Hydrogen atoms of the NHCH groups were located in difference maps and were refined freely. Compounds 2 and 3 exhibit the enol-imine form. The UV–vis spectra of the three compounds have been studied in organic solvents of different polarity, and in basic and acidic media, and were found helpful in understanding the tautomeric forms in these compounds; the polarity was modified by adding (CF3COOH) or [(C2H5)3N] to the solvent. All three compounds have been characterized by elemental analysis, UV–vis, FTIR, NMR and MS

Bacteria isolated from milk of dairy cows with and without clinical mastitis in different regions of Australia and their AMR profiles

Mastitis is the most common disease in dairy cattle worldwide. The objectives of this study were to estimate the prevalence of different bacterial species associated with mastitis from dairy herds located in geographically and climatically distinct zones in Australia, and to evaluate the antimicrobial susceptibility of the isolated bacteria. Quarter-level milk samples (n = 419) were collected from 151 mastitis cases and 268 healthy controls originating from 18 dairy herds located in tropical (Northern Queensland), subtropical (Southeast Queensland) and temperate zones (Victoria) between March and June 2019. Milk samples were cultured, and the isolated bacteria were grouped into six groups: Enterobacteriaceae spp.; Streptococcus spp.; Staphylococcus aureus, non-aureus staphylococci (NAS); Bacillus spp.; and Others. Mixed effects conditional logistic regression models were applied to quantify the association between the prevalence of each bacterial group and the herd zone and bulk milk tank somatic cell counts (BMTSCC). Of the 205 isolates, 102 (50%) originated from mastitis cases, and 103 (50%) from controls. Staphylococci were the most prevalent (NAS 32% and S. aureus 11%). Contagious mastitis bacteria were more prevalent in Victoria compared to Queensland dairy herds. NAS species (P 300,000 cells/mL compared with herds with low BMTSCC ≤150,000 cells/mL. Enterobacteriaceae and Streptococcus spp. groups showed high resistance rates to 1 (51 and 47%, respectively), and 2 (11 and 23%, respectively), antimicrobials. More than one third of the Enterobacteriaceae (48%) and Others (43%) groups spp. were resistant to at least three antimicrobials. This study provided a unique opportunity to investigate the prevalence of mastitis-associated bacteria in clinical cases and in apparently healthy controls. The findings of this study help inform mastitis control and antimicrobial stewardship programs aimed to reduce the prevalence of mastitis and antimicrobial resistance in dairy herds

29. No association between MTHFR C677T polymorphism and congenital heart disease in Saudi Arabian population

Congenital heart diseases (CHD) are the most common birth defects in the world. It is a major cause of childhood mortality and morbidity worldwide with about 7 per 1000 live birth. Studies suggest that Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD), but the evidence remains inconclusive. The aim of this study is to determine whether this association exists in the Saudi Arabian population.MethodDNA sequencing was used to detect genotype MTHFR C677T in 75 CHD patients and 100 ethnically similar controls. The type of cardiac defect was diagnosed by cardiovascular specialist and confirmed by echocardiographic.ResultsThe distribution of the MTHFR 677C >T SNP genotypes and alleles in both CHD and control groups were 70.0% CC, 26.0% CT, 4.0% TT in cases and 70.8% CC, 25.4% CT, 3.8% TT in controls. The T allele frequency was 17.0% in cases and 16.5% in controls. The difference between genotypes and alleles was not statistically significant between controls and the CHD groups.ConclusionWe did not find sufficient evidence for an association between MTHFR C677T genotype and congenital heart disease in Saudi Arabian population. We agree that the sample size is a limitation to our above conclusions

Sequence analysis of the VSX1 and SOD1 genes in families with Keratoconus and a review of the literature

AbstractObjectiveKeratoconus (KC) is a non-inflammatory disorder of the cornea in which the cornea becomes thin and conical, inducing myopia and irregular astigmatism and resulting in mild to marked impairment of vision. The present study was designed to screen two candidate KC genes to identify pathogenic sequence variants responsible for KC in Saudi families.MethodsPeripheral blood samples from members of five Saudi families with KC from the Northern region were collected. Genomic DNA was isolated, and bidirectional sequencing was performed of all coding exons of VSX1 and SOD1 genes using Sanger sequencing.ResultsAll five of the KC families showed a pattern of autosomal recessive inheritance. Phenotyping of these families was performed by a senior ophthalmologist. Sequence analysis of the VSX1 and SOD1 genes failed to reveal any pathogenic sequence variant that could account for KC in the affected individuals.ConclusionOur failure to detect sequence variants in two of the known KC associated genes triggers an interest in other known KC candidate genes, including miR-184, DOCK9, IL1RN and SLC4A11. Future genotyping with dense SNP arrays followed by exome sequencing in these families will be a useful approach to identify the gene(s) underlying KC in this Saudi cohort, which may be different from those reported elsewhere

A novel homozygous TPM1 mutation in familial pediatric hypertrophic cardiomyopathy and in silico screening of potential targeting drugs.

Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. While sarcomeric gene mutations explain many HCM cases, the genetic basis of about half of HCM cases remains elusive. Here we aimed to identify the gene causing HCM in a non-consanguineous Saudi Arabian family with affected family members and a history of sudden death. The impact of the identified mutation on protein structure and potential drug targets were evaluated in silico. Triplets (two HCM subjects and one patent ductus arteriosus (PDA) case) and unaffected parents were screened by targeted next-generation sequencing (NGS) for 181 candidate cardiomyopathy genes. In silico structural and functional analyses, including protein modeling, structure prediction, drug screening, drug binding, and dynamic simulations were performed to explore the potential pathogenicity of the variant and to identify candidate drugs. A homozygous missense mutation in exon 1 of TMP1 (assembly GRCh37-chr15: 63340781; G>A) was identified in the triplets [two HCM and one patent ductus arteriosus (PDA)] that substituted glycine for arginine at codon 3 (p.Gly3Arg). The parents were heterozygous for the variant. The mutation was predicted to cause a significant and deleterious change in the TPM1 protein structure that slightly affected drug binding, stability, and conformation. In addition, we identified several putative TPM1-targeting drugs through structure-based in silico screening. TPM1 mutations are a common cause of HCM and other congenital heart defects. To date, TPM1 has not been associated with isolated PDA; to our knowledge, this is the first report of the homozygous missense variation p.Gly3Arg in TPM1 associated with familial autosomal recessive pediatric HCM and PDA. The identified candidate TPM1 inhibitors warrant further prospective investigation.This research was supported by the Strategic Technologies Programs of the National Plan for Science, Technology and Innovation (MAARIFAH), Kingdom of Saudi Arabia. Project No: 12-MED3174-05, through the Science and Technology Unit (STU), Taibah University, Al Madinah Al Munawwarah, Kingdom of Saudi Arabia

Association between Paraoxonases Gene Expression and Oxidative Stress in Hepatotoxicity Induced by CCl 4

Objectives. The purpose of the study is to evaluate the hepatoprotective effect of rutin in carbon tetrachloride- (CCl4-) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl4. Group IV was administered rutin after 48 h of CCl4 treatment. Liver enzymes level, lipid profile, lipid peroxidation, and hydrogen peroxide were measured. The genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl4 group showed significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H2O2), and lipid profile and a significant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-δ), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl4 to control values. Conclusion. CCl4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective effect through enhancing the antioxidant genes

The Ameliorative Effect of Green Tea, Garlic and Vitamin C on Arsenic Toxicity in Male Mice: Biochemical and Histological Forensic Perspectives

Arsenic is a heavy metal with toxic effects on human health and is widely found in the environment. It is used in suicides and, hence, acquires forensic impact. Sixty adult male albino mice weighing 30-40 g were subjected to a sub-lethal dose of sodium arsenate (40 mg/kg body weight) to investigate hematological, biochemical and histopathological alterations in liver and kidney. The mice were also co-treated with green tea, garlic and vitamin C to reveal the protective role of these herbal and synthetic antioxidants. Arsenic induced significant declines in all blood parameters, while green tea, garlic and vitamin C ameliorated these affected hematological parameters. Alanine transaminase (ALT) and aspartate transaminase (AST) were significantly increased in the sodium arsenate treated group, while green tea, garlic and vitamin C ameliorated these increases in enzyme levels. Creatinine and urea were significantly increased in arsenic treated mice. These renal parameters become normal in mice co-treated with green tea, garlic and vitamin C. Arsenate-treated mice showed venous congestion, sinusoidal dilatation, mononuclear cell infiltration and periportal fibrosis in liver sections. Kidney samples from the same group revealed interstitial hemorrhages, mononuclear cell infiltration, glomerulonephritis and proximal tubular necrosis. Hepato-renal injuries were greatly reduced, particularly in animals that received both green tea and garlic. The herbs used have a potential for ameliorating and protecting against the hepato-renal toxicity caused by arsenic and need further studies. This study revealed the possibility of using liver and kidney as indicators to ascertain arsenic poisoning in forensic casework

A Flood Risk Management Program of Wadi Baysh Dam on the Downstream Area: An Integration of Hydrologic and Hydraulic Models, Jizan Region, KSA

For public safety, especially for people who dwell in the valley that is located downstream of a dam site, as well as the protection of economic and environmental resources, risk management programs are urgently required all over the world. Despite the high safety standards of dams because of improved engineering and excellent construction in recent times, a zero-risk guarantee is not possible, and accidents can happen, triggered by natural hazards, human actions, or just because the dam is aging. In addition to that is the impact of potential climate change, which may not have been taken into account in the original design. A flood risk management program, which is essential for protecting downstream dam areas, is required. Part of this program is to prepare an inundation map to simulate the impact of dam failure on the downstream areas. The Baysh dam has crucial importance both to protect the downstream areas against flooding, to provide drinking water to cities in the surrounding areas, and to use the excess water for irrigation of the agricultural areas located downstream of the dam. Recently, the Kingdom of Saudi Arabia (KSA) was affected by extraordinary rainstorm events causing many problems in many different areas. One of these events happened along the basin of the Baysh dam, which raised the alarm to the decision makers and to the public to take suitable action before dam failure occurs. The current study deals with a flood risk analysis of Wadi Baysh using an integration of hydrologic and hydraulic models. A detailed field investigation of the dam site and the downstream areas down to the Red Sea coast has been undertaken. Three scenarios were applied to check the dam and the reservoir functionality; the first scenario at 100-and 200-year return period rainfall events, the second scenario according to the Probable Maximum Precipitation (PMP), and the third scenario if the dam fails. Our findings indicated that the Baysh dam and reservoir at 100-and 200-year rainfall events are adequate, however, at the PMP the water will spill out from the spillway at ~8900 m3/s causing flooding to the downstream areas; thus, a well-designed channel along the downstream wadi portion up to the Red Sea coast is required. However, at dam failure, the inundation model indicated that a vast area of the section downstream of the dam will be utterly devastated, causing a significant loss of lives and destruction of urban areas and agricultural lands. Eventually, an effective warning system and flood hazard management system are imperative