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  1. Binding of an anticancer drug, axitinib to human serum albumin: Fluorescence quenching and molecular docking study
    Tayyab S, Izzudin MM, Kabir MZ, Feroz SR, Tee WV, Mohamad SB, et al.
    J. Photochem. Photobiol. B, Biol., 2016 Sep;162:386-94.
    PMID: 27424099 DOI: 10.1016/j.jphotobiol.2016.06.049
    Binding characteristics of a promising anticancer drug, axitinib (AXT) to human serum albumin (HSA), the major transport protein in human blood circulation, were studied using fluorescence, UV-vis absorption and circular dichroism (CD) spectroscopy as well as molecular docking analysis. A gradual decrease in the Stern-Volmer quenching constant with increasing temperature revealed the static mode of the protein fluorescence quenching upon AXT addition, thus confirmed AXT-HSA complex formation. This was also confirmed from alteration in the UV-vis spectrum of HSA upon AXT addition. Fluorescence quenching titration results demonstrated moderately strong binding affinity between AXT and HSA based on the binding constant value (1.08±0.06×10(5)M(-1)), obtained in 10mM sodium phosphate buffer, pH7.4 at 25°C. The sign and magnitude of the enthalpy change (∆H=-8.38kJmol(-1)) as well as the entropy change (∆S=+68.21Jmol(-1)K(-1)) clearly suggested involvement of both hydrophobic interactions and hydrogen bonding in AXT-HSA complex formation. These results were well supported by molecular docking results. Three-dimensional fluorescence spectral results indicated significant microenvironmental changes around Trp and Tyr residues of HSA upon complexation with AXT. AXT binding to the protein produced significant alterations in both secondary and tertiary structures of HSA, as revealed from the far-UV and the near-UV CD spectral results. Competitive drug displacement results obtained with phenylbutazone (site I marker), ketoprofen (site II marker) and hemin (site III marker) along with molecular docking results suggested Sudlow's site I, located in subdomain IIA of HSA, as the preferred binding site of AXT.
    Matched MeSH terms: Serum Albumin/metabolism*
  2. Racial disparity in the prevalence of thyroid disorder during pregnancy
    Sakinah SO, Khalid BA, Aishah AB
    Ann Acad Med Singap, 1993 Jul;22(4):563-6.
    PMID: 8257059
    A study to determine the prevalence of goitre and abnormal thyroid status during pregnancy in Malaysian women was conducted. Two hundred and three women (Malay = 85, Chinese = 47 and Indian = 71) in the third trimester and with no known thyroid disease were studied. There was a marked racial disparity in the prevalence of goitre: Indian 61%, Malay 28% and Chinese 29% (p = 0.001). The serum thyrotropic hormone (TSH) was significantly higher in Indians (median: 1.36 uIU/ml) compared to Malays (1.14 uIU/ml, p = 0.009). The serum albumin was also significantly lower in Indians (mean +/- sd; 36.12 +/- 3.9 mmol/l) compared to Malays (39.3 +/- 4.8 mmol/l) or Chinese (39.1 +/- 5.2) (p < 0.001). Thyroid antibody was detected in 14.6% of these women with no significant racial difference in its prevalence. Three women were found to be thyrotoxic but none were hypothyroid. This study found a high prevalence of goitre among the pregnant Indian women, probably related to the protein malnutrition state. The high prevalence of positive thyroid antibody in our population indicates that a high percentage of women are at risk of developing postpartum thyroiditis.
    Matched MeSH terms: Serum Albumin/metabolism
  3. Fulltext Assessing protein energy wasting in a Malaysian haemodialysis population using self-reported appetite rating: a cross-sectional study
    Sahathevan S, Se CH, Ng SH, Chinna K, Harvinder GS, Chee WS, et al.
    BMC Nephrol, 2015;16:99.
    PMID: 26149396 DOI: 10.1186/s12882-015-0073-x
    Poor appetite could be indicative of protein energy wasting (PEW) and experts recommend assessing appetite in dialysis patients. Our study aims to determine the relationship between PEW and appetite in haemodialysis (HD) patients.
    Matched MeSH terms: Serum Albumin/metabolism
  4. Protein Energy Wasting in a Cohort of Maintenance Hemodialysis Patients in Dhaka, Bangladesh
    Rahman T, Khor BH, Sahathevan S, Kaur D, Latifi E, Afroz M, et al.
    Nutrients, 2022 Apr 01;14(7).
    PMID: 35406082 DOI: 10.3390/nu14071469
    Malnutrition is associated with high rates of mortality among patients with end stage kidney disease (ESKD). There is a paucity of data from Bangladesh, where around 35,000−40,000 people reach ESKD annually. We assessed protein-energy wasting (PEW) amongst 133 patients at a single hemodialysis setting in Dhaka. Patients were 49% male, age 50 ± 13 years, 62% were on twice-weekly hemodialysis. Anthropometric, biochemical, and laboratory evaluations revealed: BMI 24.1 ± 5.2 kg/m2, mid-arm muscle circumference (MAMC) 21.6 ± 3.6 cm, and serum albumin 3.7 ± 0.6 g/dL. Based on published criteria, 18% patients had PEW and for these patients, BMI (19.8 ± 2.4 vs. 25.2 ± 5.2 kg/m2), MAMC (19.4 ± 2.4 vs. 22.2 ± 3.8 cm), serum albumin (3.5 ± 0.7 vs. 3.8 ± 0.5 g/dL), and total cholesterol (135 ± 34 vs. 159 ± 40 mg/dL), were significantly lower as compared to non-PEW patients, while hand grip strength was similar (19.5 ± 7.6 vs. 19.7 ± 7.3 kg). Inflammatory C-reactive protein levels tended to be higher in the PEW group (20.0 ± 34.8 vs. 10.0 ± 13.9 p = 0.065). Lipoprotein analyses revealed PEW patients had significantly lower low density lipoprotein cholesterol (71 ± 29 vs. 88 ± 31 mg/dL, p < 0.05) and plasma triglyceride (132 ± 51 vs. 189 ± 103 mg/dL, p < 0.05), while high density lipoprotein cholesterol was similar. Nutritional assessments using a single 24 h recall were possible from 115 of the patients, but only 66 of these were acceptable reporters. Amongst these, while no major differences were noted between PEW and non-PEW patients, the majority of patients did not meet dietary recommendations for energy, protein, fiber, and several micronutrients (in some cases intakes were 60−90% below recommendations). Malnutrition Inflammation Scores were significantly higher in PEW patients (7.6 ± 3.1 vs. 5.3 ± 2.7 p < 0.004). No discernible differences were apparent in measured parameters between patients on twice- vs. thrice-weekly dialysis. Data from a larger cohort are needed prior to establishing patient-management guidelines for PEW in this population.
    Matched MeSH terms: Serum Albumin/metabolism
  5. Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery
    Négrier C, Abdul Karim F, Lepatan LM, Lienhart A, López-Fernández MF, Mahlangu J, et al.
    Haemophilia, 2016 Jul;22(4):e259-66.
    PMID: 27333467 DOI: 10.1111/hae.12972
    INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment.
    AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting.
    METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required.
    RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP.
    CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.
    KEYWORDS: albumin fusion proteins; factor IX; haemophilia B; orthopaedic surgery; recombinant fusion proteins
    Matched MeSH terms: Serum Albumin/metabolism
  6. Fulltext C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis
    Mohd Amin AT, Zaki RA, Friedmacher F, Sharif SP
    Pediatr Surg Int, 2021 Jul;37(7):881-886.
    PMID: 33779823 DOI: 10.1007/s00383-021-04879-1
    PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC).

    METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI).

    RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p 

    Matched MeSH terms: Serum Albumin/metabolism*
  7. Fulltext Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions
    Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, et al.
    Drug Deliv, 2018 Nov;25(1):1067-1077.
    PMID: 29688069 DOI: 10.1080/10717544.2018.1464083
    Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
    Matched MeSH terms: Serum Albumin/metabolism
  8. The movement of fluorescent isothiocyanate (F.I.T.C.) labelled human albumin from blood into brain tissue examined by fluorescent technique in normal and Plasmodium knowlesi infected Macaca mulatta
    Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):251.
    PMID: 4234390
    Matched MeSH terms: Serum Albumin/metabolism*
  9. Factor affecting on the movement of protein across the blood: brain: C.S.F. barriers in Plasmodium knowlesi infected Macaca mulatta
    Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):251.
    PMID: 4234389
    Matched MeSH terms: Serum Albumin/metabolism*
  10. Evaluation of pendimethalin binding to human serum albumin: Insights from spectroscopic and molecular modeling approach
    Lee WQ, Affandi IS, Feroz SR, Mohamad SB, Tayyab S
    J Biochem Mol Toxicol, 2017 Feb;31(2).
    PMID: 27636401 DOI: 10.1002/jbt.21839
    Interaction of pendimethalin (PM) herbicide with the major transporter in human circulation, human serum albumin (HSA), was studied using fluorescence, circular dichroism (CD), and molecular modeling methods. The attenuation of the fluorescence intensity of HSA in the presence of PM revealed formation of the PM-HSA complex. Analysis of the fluorescence quenching data showed moderately strong binding affinity between PM and HSA. Both hydrophobic interactions and hydrogen bonding were suggested to stabilize the PM-HSA complex, based on thermodynamic data. Binding of PM to HSA induced perturbation in the microenvironment around the aromatic fluorophores as well as secondary and tertiary structural changes in the protein. Complexation of PM with HSA led to an increase in its thermal stability. Both site marker displacement and molecular modeling results suggested site I, located in subdomain IIA as the preferred binding site of PM on HSA.
    Matched MeSH terms: Serum Albumin/metabolism*
  11. Bromophenol blue binding to mammalian albumins and displacement of albumin-bound bilirubin
    Kim BB, Abdul Kadir H, Tayyab S
    Pak J Biol Sci, 2008 Oct 15;11(20):2418-22.
    PMID: 19137852
    Interaction of bromophenol blue (BPB) with serum albumins from different mammalian species, namely, human (HSA), bovine (BSA), goat (GSA), sheep (SSA), rabbit (RbSA), porcine (PSA) and dog (DSA) was studied using absorption and absorption difference spectroscopy. BPB-albumin complexes showed significant differences in the spectral characteristics, i.e., extent of bathochromic shift and hypochromism relative to the spectral features of free BPB. Absorption difference spectra of these complexes also showed variations in the position of maxima and absorption difference (deltaAbs.) values. Absorption difference spectra of different bilirubin (BR)-albumin complexes showed a significant blue shift accompanied by decrease in deltaAbs. values in presence of BPB which were indicative of the displacement of bound BR from its binding site in BR-albumin complexes. These changes in the difference spectral characteristics of BR-albumin complexes were more marked at higher BPB concentration. However, the extent of these changes was different for different BR-albumin complexes. Taken together, all these results suggest that BPB partially shares BR binding site on albumin and different mammalian albumins show differences in the microenvironment of the BR/BPB binding site.
    Matched MeSH terms: Serum Albumin/metabolism*
  12. Interaction of a tyrosine kinase inhibitor, vandetanib with human serum albumin as studied by fluorescence quenching and molecular docking
    Kabir MZ, Feroz SR, Mukarram AK, Alias Z, Mohamad SB, Tayyab S
    J Biomol Struct Dyn, 2016 Aug;34(8):1693-704.
    PMID: 26331959 DOI: 10.1080/07391102.2015.1089187
    Interaction of a tyrosine kinase inhibitor, vandetanib (VDB), with the major transport protein in the human blood circulation, human serum albumin (HSA), was investigated using fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking analysis. The binding constant of the VDB-HSA system, as determined by fluorescence quenching titration method was found in the range, 8.92-6.89 × 10(3 )M(-1) at three different temperatures, suggesting moderate binding affinity. Furthermore, decrease in the binding constant with increasing temperature revealed involvement of static quenching mechanism, thus affirming the formation of the VDB-HSA complex. Thermodynamic analysis of the binding reaction between VDB and HSA yielded positive ΔS (52.76 J mol(-1) K(-1)) and negative ΔH (-6.57 kJ mol(-1)) values, which suggested involvement of hydrophobic interactions and hydrogen bonding in stabilizing the VDB-HSA complex. Far-UV and near-UV CD spectral results suggested alterations in both secondary and tertiary structures of HSA upon VDB-binding. Three-dimensional fluorescence spectral results also showed significant microenvironmental changes around the Trp residue of HSA consequent to the complex formation. Use of site-specific marker ligands, such as phenylbutazone (site I marker) and diazepam (site II marker) in competitive ligand displacement experiments indicated location of the VDB binding site on HSA as Sudlow's site I (subdomain IIA), which was further established by molecular docking results. Presence of some common metal ions, such as Ca(2+), Zn(2+), Cu(2+), Ba(2+), Mg(2+), and Mn(2+) in the reaction mixture produced smaller but significant alterations in the binding affinity of VDB to HSA.
    Matched MeSH terms: Serum Albumin/metabolism
  13. Characterization of the binding of an anticancer drug, lapatinib to human serum albumin
    Kabir MZ, Mukarram AK, Mohamad SB, Alias Z, Tayyab S
    J. Photochem. Photobiol. B, Biol., 2016 Jul;160:229-39.
    PMID: 27128364 DOI: 10.1016/j.jphotobiol.2016.04.005
    Interaction of a promising anticancer drug, lapatinib (LAP) with the major transport protein in human blood circulation, human serum albumin (HSA) was investigated using fluorescence and circular dichroism (CD) spectroscopy as well as molecular docking analysis. LAP-HSA complex formation was evident from the involvement of static quenching mechanism, as revealed by the fluorescence quenching data analysis. The binding constant, Ka value in the range of 1.49-1.01×10(5)M(-1), obtained at three different temperatures was suggestive of the intermediate binding affinity between LAP and HSA. Thermodynamic analysis of the binding data (∆H=-9.75kJmol(-1) and ∆S=+65.21Jmol(-1)K(-1)) suggested involvement of both hydrophobic interactions and hydrogen bonding in LAP-HSA interaction, which were in line with the molecular docking results. LAP binding to HSA led to the secondary and the tertiary structural alterations in the protein as evident from the far-UV and the near-UV CD spectral analysis, respectively. Microenvironmental perturbation around Trp and Tyr residues in HSA upon LAP binding was confirmed from the three-dimensional fluorescence spectral results. LAP binding to HSA improved the thermal stability of the protein. LAP was found to bind preferentially to the site III in subdomain IB on HSA, as probed by the competitive drug displacement results and supported by the molecular docking results. The effect of metal ions on the binding constant between LAP and HSA was also investigated and the results showed a decrease in the binding constant in the presence of these metal ions.
    Matched MeSH terms: Serum Albumin/metabolism*
  14. Fulltext Drug Delivery System for Refractory Cancer Therapy via an Endogenous Albumin Transport System
    Ishima Y, Maruyama T, Otagiri M, Ishida T
    Chem Pharm Bull (Tokyo), 2020;68(7):583-588.
    PMID: 32611995 DOI: 10.1248/cpb.c20-00026
    A unique phenomenon in solid tumors, the enhanced permeability and retention (EPR) effect is now well known in the development of macromolecular anticancer therapy. However, cancers with low vascular permeability have posed a challenge for these EPR based therapeutic systems. An intrinsic vascular modulator, such as nitric oxide (NO), could augment the endogenous EPR effect. However, the most important aim has been to construct an effective NO delivery system for cancer. Since it is well known that human serum albumin is one of the most important endogenous NO transport proteins in human circulation, for more than a decade we have demonstrated that S-nitrosated human serum albumin dimer (SNO-HSA-Dimer) becomes an enhancer of the EPR effect. Here, we summarize the enhanced effect of SNO-HSA-Dimer on the anticancer effect of macromolecular anticancer drugs such as PEGylated liposomal doxorubicin (Doxil®). In C26-bearing mice with highly permeable vasculature, SNO-HSA-Dimer is able to increase more 3-fold the tumor accumulation of these anticancer drugs, thereby tripling their anticancer effects. Interestingly, the tumor accumulation of Doxil® in B16-bearing mice, which are characterized by a low permeable vasculature, increased more than 6-fold in the presence of SNO-HSA-Dimer, and the improved accumulation of Doxil® led to both increased survival and decreased tumor volume. These results strongly suggest that the more cancer is refractory, the more the SNO-HSA-Dimer could enhance the EPR effect via an endogenous albumin transport (EAT) system. Accordingly, we conclude that the EAT system is promising as a drug delivery system (DDS) strategy for refractory cancer therapy.
    Matched MeSH terms: Serum Albumin/metabolism
  15. In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract
    Iqbal MO, Yahya EB
    Tissue Cell, 2021 Oct;72:101525.
    PMID: 33780659 DOI: 10.1016/j.tice.2021.101525
    Aminoglycoside antibiotics are widely employed clinically due to their powerful bactericidal activities, less bacterial resistance compared to beta lactam group and low cost. However, their use has been limited in recent years due to their potential induction of nephrotoxicity. Here we investigate the possibility of reversing nephrotoxicity caused by gentamicin in rat models by using ethanolic crude extract of the medicinal plant Jatropha Mollissima. Nephrotoxic male Wistar rats was obtained by gentamicin antibiotic, which then treated with two doses of J. mollissima crude extract for 3 weeks with monitoring their parameter in weekly base. Our results indicate that J. mollissima crude extract at both doses has strong protection ability against gentamicin nephrotoxicity, most of tested parameters backed to normal values after few days from the administration of the crude extract, which could be due to the antagonized the biochemical action of gentamicin on the proximal tubules of the kidney. The results of histopathologic analysis showed observable improvement in J. mollissima treated groups compared with untreated groups. Our findings suggests the J. mollissima has exceptional nephron protection potentials able to reverse the nephrotoxicity caused by gentamicin antibiotic.
    Matched MeSH terms: Serum Albumin/metabolism
  16. BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus
    Iqbal J, Rehman A, Abbasi MA, Siddiqui SZ, Khalid H, Laulloo SJ, et al.
    Pak J Pharm Sci, 2020 Jan;33(1):149-160.
    PMID: 32122843
    A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.
    Matched MeSH terms: Serum Albumin/metabolism*
  17. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent
    Harizal SN, Mansor SM, Hasnan J, Tharakan JK, Abdullah J
    J Ethnopharmacol, 2010 Sep 15;131(2):404-9.
    PMID: 20643198 DOI: 10.1016/j.jep.2010.07.013
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic.
    AIM: The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats.
    METHODOLOGY: Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity.
    RESULT: No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups.
    CONCLUSION: Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters.
    Matched MeSH terms: Serum Albumin/metabolism*
  18. Fulltext Spectrofluorometric and molecular docking studies on the binding of curcumenol and curcumenone to human serum albumin
    Hamdi OA, Feroz SR, Shilpi JA, Anouar el H, Mukarram AK, Mohamad SB, et al.
    Int J Mol Sci, 2015;16(3):5180-93.
    PMID: 25756376 DOI: 10.3390/ijms16035180
    Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M-1) in comparison to curcumenol (1.97 × 104 M-1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of -6.77 kcal·mol-1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be -5.72 and -5.74 kcal·mol-1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding.
    Matched MeSH terms: Serum Albumin/metabolism*
  19. Multispectroscopic and molecular modeling approach to investigate the interaction of flavokawain B with human serum albumin
    Feroz SR, Mohamad SB, Bujang N, Malek SN, Tayyab S
    J Agric Food Chem, 2012 Jun 13;60(23):5899-908.
    PMID: 22624666 DOI: 10.1021/jf301139h
    Interaction of flavokawain B (FB), a multitherapeutic flavonoid from Alpinia mutica with the major transport protein, human serum albumin (HSA), was investigated using different spectroscopic probes, i.e., intrinsic, synchronous, and three-dimensional (3-D) fluorescence, circular dichroism (CD), and molecular modeling studies. Values of binding parameters for FB-HSA interaction in terms of binding constant and stoichiometry of binding were determined from the fluorescence quench titration and were found to be 6.88 × 10(4) M(-1) and 1.0 mol of FB bound per mole of protein, respectively, at 25 °C. Thermodynamic analysis of the binding data obtained at different temperatures showed that the binding process was primarily mediated by hydrophobic interactions and hydrogen bonding, as the values of the enthalpy change (ΔH) and the entropy change (ΔS) were found to be -6.87 kJ mol(-1) and 69.50 J mol(-1) K(-1), respectively. FB binding to HSA led to both secondary and tertiary structural alterations in the protein as revealed by intrinsic, synchronous, and 3-D fluorescence results. Increased thermal stability of HSA in the presence of FB was also evident from the far-UV CD spectral results. The distance between the bound ligand and Trp-214 of HSA was determined as 3.03 nm based on the Förster resonance energy transfer mechanism. Displacement experiments using bilirubin and warfarin coupled with molecular modeling studies assigned the binding site of FB on HSA at domain IIA, i.e., Sudlow's site I.
    Matched MeSH terms: Serum Albumin/metabolism*
  20. Fulltext A comparative analysis on the binding characteristics of various mammalian albumins towards a multitherapeutic agent, pinostrobin
    Feroz SR, Sumi RA, Malek SN, Tayyab S
    Exp Anim, 2015;64(2):101-8.
    PMID: 25519455 DOI: 10.1538/expanim.14-0053
    The interaction of pinostrobin (PS), a multitherapeutic agent with serum albumins of various mammalian species namely, goat, bovine, human, porcine, rabbit, sheep and dog was investigated using fluorescence quench titration and competitive drug displacement experiments. Analysis of the intrinsic fluorescence quenching data revealed values of the association constant, K(a) in the range of 1.49 - 6.12 × 10(4) M(-1), with 1:1 binding stoichiometry. Based on the PS-albumin binding characteristics, these albumins were grouped into two classes. Ligand displacement studies using warfarin as the site I marker ligand correlated well with the binding data. Albumins from goat and bovine were found to be closely similar to human albumin on the basis of PS binding characteristics.
    Matched MeSH terms: Serum Albumin/metabolism*
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