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1.
Molecules ; 27(18)2022 Sep 08.
Article in English | MEDLINE | ID: mdl-36144555

ABSTRACT

The special features of cyclodextrins (CDs), hydrophilic outer surfaces and hydrophobic inner surfaces, allow for development of inclusion complexes. The two bioactive strong antioxidant hepatoprotective compounds, Morin and vitamin E, are water insoluble. The present study aimed to prepare Morin-vitamin E-ß-cyclodextrin inclusion complex loaded chitosan nanoparticles (M-Vit.E-CD-CS NPs) and to examine their hepatoprotective efficacy against arsenic-induced toxicity in a murine model. The NPs were characterized by FTIR, DLS, NMR, DSC, XRD, AFM, and a TEM study. The NPs were spherical in shape, 178 ± 1.5 nm in size with a polydispersity index (PDI) value of 0.18 and a zeta potential value of −22.4 ± 0.31 mV, with >50% encapsulation and drug loading efficacy. Mice were exposed to arsenic via drinking water, followed by treatment without or with the NPs on every alternate day up to 30 days by oral gavaging. Administration of NPs inhibited the arsenic-induced elevation of liver function markers, inflammatory and proapoptotic factors, reactive oxygen species (ROS) production, alteration in the level of blood parameters and antioxidant factors, and liver damage, which was measured by different biochemical assays, ELISA, Western blot, and histological study. Organ distribution of nanoparticles was measured by HPLC. M-Vit.E-CD-CS NPs showing potent hepatoprotective activity may be therapeutically beneficial.


Subject(s)
Arsenic , Chitosan , Drinking Water , Nanoparticles , beta-Cyclodextrins , Animals , Antioxidants/pharmacology , Arsenic/toxicity , Chitosan/chemistry , Chitosan/pharmacology , Disease Models, Animal , Drug Carriers/chemistry , Flavones , Mice , Nanoparticles/chemistry , Reactive Oxygen Species , Vitamin E , Vitamins , beta-Cyclodextrins/chemistry
2.
Nanoscale Adv ; 4(13): 2857-2872, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-36132010

ABSTRACT

Chronic exposure to arsenic over a period of time induces toxicity, primarily in the liver but gradually in all systems of the body. Morin hydrate (MH; 2',3,4',5,7-pentahydroxyflavone), a potent flavonoid abundantly present in plants of the Moraceae family, is thought to be a major bioactive compound that may be used to prevent a wide range of disease pathologies including hepatotoxicity. Therapeutic applications of morin (MOR) are however seriously constrained because of its insolubility, poor bioavailability, high metabolism and rapid elimination from the human body. Nanoformulation of MOR is a possible solution to these problems. In the present study we investigated the effectiveness of morin encapsulated chitosan nanoparticles (MCNPs) against arsenic induced liver damage in mice. MNCPs with an average diameter of 124.5 nm, a zeta potential of +16.2 mV and an encapsulation efficiency of 78% were prepared. Co-treatment of MOR and MCNPs by oral gavage on alternate days reduced the serum levels of AST, ALT, and ALP that were elevated in arsenic treated mice. The efficiency of MCNPs was found to be nearly 4 times higher than that of free MOR. Haematological and serum biochemical parameters including lipid profiles altered by arsenic were normalized following MCNP treatment. Arsenic deposition was lowered in the presence of MCNPs. Administration of MCNPs markedly inhibited ROS generation and elevated MDA levels in arsenic exposed mice. The level of hepatic antioxidant factors such as nuclear Nrf2 (Nrf2), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), GSH peroxidase (GPx), glutathione-S-transferase (GST), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1(NQO1) were markedly enhanced in the arsenic + MCNP group. Treatment by MCNPs prevented the arsenic induced damage of tissue histology. Also, MCNPs suppressed the arsenic induced pro- and anti-apoptotic parameters and attenuated the level of inflammatory mediators. Our data suggest that MCNPs are good hepatoprotective agents compared to free morin against arsenic induced toxicity and the protective effect results from its strong antioxidant, antiapoptotic and anti-inflammatory properties.

3.
Intervirology ; 51(4): 275-84, 2008.
Article in English | MEDLINE | ID: mdl-18987483

ABSTRACT

OBJECTIVES: This unmatched case-control study aimed at determining the molecular epidemiology and clinical significance of HBV genotypes, core promoter (CP) and precore (PC) mutations in Eastern India. METHODS: Serological, biochemical and molecular assays were used to examine antigens, ALT, genotypes, mutations and viremia among 106 inactive carriers and 183 chronic liver disease (CLD) patients. RESULTS: Male gender (p < 0.001), HBeAg positivity (p = 0.050), high ALT (p < 0.001), high viremia (p < 0.001), CP mutations (p < 0.001), and genotypes A (p < 0.001) and C (p = 0.027) were significantly associated with CLD. Subjects infected with genotypes A and C had significantly higher prevalence of BCP mutations (p < 0.001), and low incidence of PC mutation (p < 0.001 and p = 0.047, respectively). Prevalence of genotype D was significantly higher among subjects with history of familial/childhood jaundice, while genotypes A and C were frequent among subjects with possible percutaneous exposure. CONCLUSIONS: Significant differences in risk factors and disease manifestation do exist among patients infected with different HBV genotypes. Genotypes A and C are frequently found among chronic liver disease patients, while genotype D is associated with inactive HBeAg-negative infections. This evaluation of clinical relevance of HBV genotypes, mutations and risk factors may be useful in disease prognosis, management and prevention strategies.


Subject(s)
Hepatitis B Core Antigens/genetics , Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/virology , Mutation , Adult , Alanine Transaminase/blood , Case-Control Studies , Female , Genotype , Hepatitis B Antigens/blood , Humans , India/epidemiology , Liver/pathology , Male , Middle Aged , Molecular Epidemiology , Viremia
4.
Virology ; 382(2): 190-8, 2008 Dec 20.
Article in English | MEDLINE | ID: mdl-18952249

ABSTRACT

HBx genetic variability was explored in the Eastern Indian population with low HCC incidence. DNase I sensitive HBV DNA was detected in 53% samples, which differed significantly between clinical groups (P<0.001). HBV genotypes A (Aa/A1), C (Cs/C1) and D (D1, D2, D3, D5) were detected in 37.5%, 18.7% and 43.7% samples respectively. Population specific signature HBx residues A(36), V(88), S(101) in Aa/A1 and residues P(41), Q(110) in D5 were detected. Mutations T(127), M(130) and I(131) were detected in 66.7%, 91% and 75% of genotype A, C and D5 samples respectively. Very low occurrence of HCC associated mutations (V(5)M/L, P(38)S, and H(94)Y) and absence of C-terminal deletions were observed. Our study shows that HBV genotype associated clinically important HBx variations may evolve and act distinctly in different geo-ethnic populations. Further studies on HBx functions from the perspective of genetic variability are essential for the better understanding of the clinical significance of HBV.


Subject(s)
Hepatitis B virus/genetics , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/virology , Trans-Activators/genetics , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , Carrier State/virology , Consensus Sequence , DNA, Viral/blood , DNA, Viral/genetics , Evolution, Molecular , Genetic Variation , Genotype , Hepatitis B virus/classification , Hepatitis B virus/isolation & purification , Humans , India , Molecular Sequence Data , Phylogeny , Polymorphism, Single Nucleotide , Protein Structure, Tertiary , Sequence Homology, Amino Acid , Trans-Activators/chemistry , Viral Regulatory and Accessory Proteins , Virulence/genetics
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