Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (
Acacia hydaspica belongs to family leguminosae possess antioxidant, anti-inflammatory and anticancer activities. During our search for antioxidant compounds from A. hydaspica, we carried out bioassay guided fractionation and obtained antioxidant compounds with free radical scavenging activity.The polyphenol compounds in the plant extract of A. hydaspica were isolated by combination of different chromatographic techniques involving vacuum liquid chromatography and medium pressure liquid chromatography. The structural heterogeneity of isolated compounds was characterized by high pressure liquid chromatography, MS-ESI and NMR spectroscopic analyses. The antioxidant potential of isolated compounds has been investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging potential, hydroxyl radical scavenging potential, ferric reducing/antioxidant power (FRAP) model systems and total antioxidant capacity measurement.The isolated compounds show the predominance of signals representative of 7-O-galloyl catechins, catechins and methyl gallate. Flash chromatographic separation gives 750 mg of 7-O galloyl catechin, 400 mg of catechin and 150 mg of methyl gallate from 4 g loaded fraction on ISCO. Results revealed that C1 was the most potent compound against DPPH (EC50 1.60 ± 0.035 µM), nitric oxide radical (EC50 6 ± 0.346 µM), showed highest antioxidant index (1.710 ± 0.04) and FRAP [649.5 ± 1.5 µM Fe(II)/g] potency at 12.5 µM dose compared to C2, C3 and standard reference, whereas C3 showed lower EC50 values (4.33 ± 0.618 µM) in OH radical scavenging assay.Present research reports for the first time the antioxidant activity of polyphenolic compounds of A. hydaspica. Result showed good resolution and separation from other constituents of extract and method was found to be simple and precise. The isolation of catechin from this new species could provide a varied opportunity to obtain large quantities of catechin and catechin isomers beside from green tea. Free radical scavenging properties of isolated catechin isomers from A. hydaspica merit further investigations for consumption of this plant in oxidative stress related disorders.
Acacia hydaspica R. Parker, family leguminosae, is a medicinally important plant. Different plant parts are used in various ailments in folk medicine. The current study aimed at investigating the in vitro antioxidant, anti-hemolytic and anticancer activity of A. hydaspica. Antioxidant potential was assessed using DPPH, ABTS and •OH, scavenging of H2O2, inhibition of lipid peroxidation and β-carotene bleaching inhibition assays. Anti-hemolytic activity was assessed using H2O2 induced hemolysis of RBCs. Anticancer potential was assessed using MTT assay. Spectrometric methods and HPLC-DAD analysis was performed for phytochemical screening. EC50 values based on reduction of DPPH, ABTS and •OH, scavenging of H2O2, inhibition of lipid peroxidation and β-carotene bleaching for AHB, AHE and AHM were generally lower manifesting potential antiradical capacities. The fractions also exhibited significant (P <0.001) anti-hemolytic potential. Regarding IC50 values for anticancer activity against HCC-38 and MDA-MB-361 cancer cell lines; AHB, AHE and AHM exhibited significant (P <0.001) cyto-selection indices. Plant extracts showed no cytotoxicity against normal Vero cells (IC50 > 250 μg/ml). While significant (P <0.001) cytotoxicity was elicited by these extract/fractions against cancer cell lines. AHE was the most effective and IC50 was found to be 29.9 ± 0.909 μg/ml (SI = 9.83) and 39.5 ± 0.872 μg/ml (SI = 7.44) against MDA-MB-361 and HCC-38 cancer cells respectively. Higher amounts of TPC and TFC were exhibited by AHE and AHB as compared to other fractions. Gallic acid, catechin and myricetin were identified in AHE whereas gallic acid and catechin were identified in AHB by HPLC. The presence of bioactive constituents in AHE and AHB might be responsible for antioxidant, anti-hemolytic and anticancer activities.
Abstract Background Cerebral palsy (CP) is considered as the main cause of severe physical impairment and malnutrition in children. This cross-sectional study intended to survey the nutritional status of children cerebral palsy in Riyadh, Saudi Arabia. Methods We examined 74 children (age: 1–10 yrs) with CP, who attended Sultan Bin Abdulaziz Humanitarian City (SBAHC), Riyadh Saudi Arabia. Data on age, general demographics, nutritional status, and dietary intake were collected. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for his/her weight for age, weight for height, height for age and body mass index for age were ≤ −2.0 standard deviation (SD) using WHO growth standards. Multivariable logistic regression identified the factors associated with nutritional indicators. Results More than half (56.4%) of the children with cerebral palsy were malnourished as they had z-score below <−2 SD in at least one of the four indicators. Thinness (50%) was the most common form of malnutrition, followed by underweight, stunting, and wasting. Arm anthropometrics gave similar results on the percent number of malnourished children. Factors that were independently associated with malnutrition with an adjusted OR (aOR) were as follow: age ≤ 5 yrs. (aOR: 4.29); presence of cognitive impairment (aOR: 4.13); presence of anemia (aOR: 3.41) and inadequate energy intake (aOR: 4.86) (p, for all trends <0.05). Conclusion Children with cerebral palsy of the current study have impaired growth and nutritional status as assessed by all four common nutritional status indicators. Further large-scale community-based studies for in-depth evaluation of nutritional status and growth patterns in children with CP are needed.
Abstract Aucubin (AU) is one of the widespread compounds belonging to the group of iridoid glycosides, which possesses numerous beneficial properties. Nonylphenol (NP), is a synthetic environmental toxicant that has the potential to cause male infertility through excessive production of reactive oxygen species. In the current study, the remedial potential of Aucubin was assessed against NP-generated testicular damage in male rats. Animals were distributed into four groups and treated for 56 days in this study. Control-group (0.1% DMSO + food), NP group (100 µg/kg), NP + AU group (100 µg/kg + 5 mg/kg) and AU group (5 mg/kg). NP exposure significantly ( p < 0.05) reduced the activity of antioxidant enzymes i.e., glutathione reductase, catalase (CAT), superoxide dismutase, glutathione peroxidase (GPx), and total protein content (TPC), whereas the level of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) was enhanced substantially ( p < 0.05). Treatment with AU substantially ( p < 0.05) recovered activities of antioxidant enzymes, TPC, ROS, and TBARS levels. Moreover, decrease in the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone, sperm count, motility, sperm membrane integrity, and the number of spermatocytes of different stages along with the level of steroidogenic enzymes i.e., 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and B-cell lymphoma 2 (Bcl-2) by NP administration were recovered to control values by AU treatment. However, AU mitigated the sperm abnormalities (head/midpiece/tail), the number of dead sperms, and proapoptotic proteins i.e., Bcl-2 associated X protein (Bax), caspase-9, and caspase-3 that were increased by NP. Besides, AU treatment recovered the NP-induced potential histopathological alterations in the testicular tissues such as the height of epithelium, seminiferous tubules diameter as well as the height of tunica propria. Overall, NP-induced toxicity was effectively recuperated by the AU administration. These results indicate that AU might be considered as a potential protective agent against testicular damage. The observed protection may be due to its antioxidant, anti-apoptotic, anti-inflammatory and androgenic potential.
The present study aims to assess the effect of a heavy metal burden on general health, biochemical parameters, an antioxidant enzyme, and reproductive hormone parameters in adult male brick kiln workers from Pakistan. The study participants (n = 546) provided demographic data including general health as well as body mass index. Blood was collected to quantitatively assess hematological, biochemical, and reproductive hormone parameters as well as heavy metal concentrations using both atomic absorption spectroscopy (AAS) and particle-induced X-ray emission (PIXE). The data showed that 10% of the brick kiln workers were underweight and 10% obese (P = 0.059), with workers also reporting multiple health issues. Heavy metal concentrations utilizing AAS revealed significantly (p = 0.000) higher levels of cadmium, chromium, and nickel, while PIXE detected more than permissible levels of Si, P, S, Cl, K, Ca, Zn, Ti (p = 0.052), Mn (p = 0.017), Fe (p = 0.055), Co (p = 0.011), Ni (p = 0.045), and Cu (p = 0.003), in the blood of kiln workers. Moreover, a significant increase in platelet count (P = 0.010), a decrease in sodium dismutase levels (p = 0.006), a major increase in reactive oxygen species (p = 0.001), and a reduction in protein content (p = 0.013) were evident. A significant increase in cortisol levels (p = 0.000) among the workers group was also observed. The concentration of LH and FSH increased significantly (p = 0.000), while that of testosterone decreased (p = 0.000) in the worker group compared with controls. A significant inverse relationship was found between cortisol, LH (r = - 0.380), and FSH (r = - 0.946), while a positive correlation between cortisol and testosterone was also evident (r = 0.164). The study concludes that increased heavy metal burden in the blood of brick kiln workers exposes them to the development of general and reproductive health problems due to compromised antioxidant enzyme levels, increased oxidative stress conditions, and a disturbing reproductive axis.
Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function; they are characterized by extensive genetic and clinical variability. We performed clinical, genetic, biochemical, and molecular analyses on two consanguineous families with microcephaly exhibiting an NDD. Detailed clinical investigation and molecular diagnosis were performed using whole-exome sequencing (WES), followed by Sanger sequencing for the affected families. WES revealed disease-causing homozygous variants in two families associated with microcephaly and NDDs. In family A and family B, we identified two previously reported homozygous variants (c.3978G>A; Trp1326* and c.4309C>A; p.Arg1437Ser) in the ASPM gene. Both the variants were further confirmed using bi-directional Sanger sequencing. In the present study, we presented literature review regarding the NDDs and microcephaly associated with ASPM pathogenesis. These findings contribute to studies of genotype–phenotype correlation, genetic counseling of the families, inclusion of ASPM in newborn screening, and further understanding of human brain function and development.
Viral hepatitis is the major contributor to liver cirrhosis and hepatocellular carcinoma (HCC). Studies indicated that the co-infection of hepatitis C and hepatitis B virus also prompts liver damage progression. Therefore, in the present study, the prevalence of HCV-HBV co-infection and the impact of HCV-HBV co-infection on the progression of liver damage was evaluated amongst the HCV-infected patients in Pakistan. In this study 2500 HCV-positive patients were recruited from Pakistan. The presence and prevalence of HCV and HBV was confirmed through ELISA and nested PCR. To determine the liver damage due to viral infection levels of ALT, ALP, and total bilirubin were also determined. Diagnostic history of patients was thoroughly documented through serological tests and liver biopsy reports. Viral genotypes and viral loads were determined through multiplex polymerase chain reaction (PCR) and time PCR, respectively. The study outcomes showed that 12.5% of the HCV-infected patients were co-infected with HBV. Co-infection development was more common in females than in males, and females were at a higher risk of developing the infection (p-value = < 0.0001, OR = 2.437). Despite the variation among different age groups, there was no significant difference in co-infection prevalence. HCV genotype 3a was found to be most prevalent while in HBV genotype D was found to be prevalent among the patients. The HCV patients frequently developed co-infection with HBV genotype D. It was also determined that viral load for HBV genotype D was higher compared to non-D genotypes while for HCV viral load was higher in non-3a genotypes. This study evaluated the prevalence of HCV and HBV co-infection among HCV-positive patients, revealing that 12.5% patients were co-infected with HBV. Co-infection was more common in females, who had a higher risk of developing it. The study also revealed that HBV genotype D was the most prevalent in co-infected patients, with no significant age-related differences in co-infection rates.
This cross-sectional study was conducted to investigate nutritional and immunological status of colorectal cancer (CRC) patients in a little-studied population from developing country, Pakistan. Data on 81 CRC patients and 37 healthy controls (HCs) were collected on nutritional status, nutrient intake, percent body fat (%BF), selected immunological parameters, phytochemical index (PI), healthy eating index (HEI), and prognostic nutrition index (PNI). Blood samples were used for immunological and antiradical defense potential (expressed as 50% hemolysis time; HT50). Results show 40/81 (49.4%) patients reported weight loss in past 3–6 mo, Significant differences were found in HEI values between patients vs. HCs, and between patients in low vs. high PNI groups (P, for all trends <0.05). Patients in the higher PNI group were heavier, had higher % BF, higher energy intake, and higher PI score as compared to patients in the low PNI group (P < 0.05). Low PNI was positively associated with non-significantly lower CD4:CD8 ratios, higher B-cells and NK cells (P, for all trends >0.05), but with significantly higher hs-CRP levels, and lower HT50 values (P, for all trends <0.001). In conclusion, CRC patients in a little-studied population have compromised nutritional and immunological health with lower HEI and PNI scores.
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