No abstract

Tuberculosis is a highly communicable and chronic respiratory disease caused by pathogenic bacterium Mycobacterium tuberculosis. The drug - resistant species of Mycobacterium tuberculosis are tough to cure due to its resistant activity toward potential drugs. Available inhibitors of tuberculosis include few antimicrobial fluoroquinolone agents like ciprofloxacin, ofloxacin, and moxifloxacin to treat resistant Mycobacterium strains. Literature study elucidates that macromolecular target namely, HtrA2 of Mycobacterium tuberculosis play a dual role of protease and chaperone. These two activities are dependent on temperature, with low temperatures promoting the chaperone function and high temperatures promoting serine protease activity. Under normal physiological conditions HtrA2 acts as a quality control factor and promotes cell survival. In the present investigation, we screened fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogues based on better Docking score, absorption, distribution, metabolism and excretion screening and Lipinski's rule of 5, to find out their efficiency on resistant strain through in silico study. From the results observed, the analogues are suggested to be potent inhibitors of HtrA2 with sufficient scope for further exploration.

This study evaluates the hepatoprotective and antioxidant properties of N-acetylcysteine (NAC) on dimethylnitrosamine (DMN) induced hepatotoxicity in male Wistar albino rats. A single intraperitoneal dose of DMN (5 mg/kg b.w.) caused a significant increase in the levels of the serum marker enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamyl transpeptidase (γ-GT)) and a subsequent decrease in AST, ALT, ALP and increase in LDH and γ-GT in the liver tissue indicating hepatocellular damage. Elevation in the status of lipid peroxidation, fall in the activities of the enzymic (superoxide dismutase, catalase) and non-enzymic antioxidants (vitamin C, vitamin E) in the liver tissue further confirms oxidative stress and hepatocellular damage induced on DMN administration. Oral administration of NAC (50 mg/kg b.w.) for 7 days significantly prevented the above alterations in the status of the marker enzymes of hepatotoxicity and antioxidant parameters and restored them towards normalcy, which was further substantiated by the histopathological studies of the liver tissue. These results suggest that NAC offers hepatoprotection by ameliorating DMN-induced oxidative stress and hepatotoxicity and this protective effect was attributed to its antioxidant and free radical scavenging properties.

Background: Butyrylcholinesterase is an enzyme that may serve as a marker of metabolic syndrome. We (a) measured its level in persons with diabetes mellitus, (b) constructed a family tree of the enzyme using nucleotide sequences downloaded from NCBI. Butyrylcholinesterase was estimated colorimetrically using a commercially available kit (Randox Lab, UK). Phylogenetic trees were constructed by distance method (Fitch and Margoliash method) and by maximum parsimony method.Results: There was a negative correlation between serum total cholesterol and butyrylcholinesterase (-0.407; p < 0.05) and between serum LDL cholesterol and butyrylcholinesterase (-0.435; p < 0.05). There was no statistically significant correlation among the other biochemical parameters. In the evolutionary tree construction both methods gave similar trees, except for an inversion in the position of Sus scrofa (M62778) and Oryctolagus cuniculus (M62779) between Fitch and Margoliash, and maximum parsimony methods. Conclusion:The level of butyrylcholinesterase enzyme was inversely related to serum cholesterol; dendrogram showed that the structures from evolutionarily close species were placed near each other.

The protective effect of picroliv (PIC) obtained from Picrorhiza kurroa (family: Scrophulariaceae) against hydrazine (Hz)-induced hyperlipidemia was evaluated in rats. Hz administration (50 mg/kg, i.p.) caused an increase in triglyceride (TG), cholesterol (CHO), free fatty acids (FFA), and total lipids (TL) in both the plasma and liver tissue of rats accompanied by a fall in phospholipids (PL) in the liver tissue 24 h after its administration, indicating its hyperlipidemic property. The above abnormality was prevented by simultaneous treatment of PIC (50 mg/kg, p.o.) with Hz. Hz treatment also caused an increase in the mobility of TG and TL from adipose tissue, and these results indicate that Hz administration could cause hepatic steatosis by nonhepatocellular factors (such as mobilization of depot fats). This effect was also prevented by simultaneous treatment of PIC with Hz. PIC-alone treatment, however, did not produce any change in the status of all the lipid parameters evaluated in plasma, liver, and adipose tissues. These results indicate that increased mobilization of depot fats from adipose tissue may contribute to the development of hepatic steatosis in addition to decreased lipoprotein secretion, increased hepatic TG biosynthesis, and increased hepatic uptake of FFA. These have been reported as the mechanism responsible for the development of Hz-induced hepatic steatosis. PIC prevents Hz-induced hyperlipidemia, hepatic steatosis, and mobilization of lipids from depot fats, but the mechanism behind the protective effect of PIC remains to be elucidated.

No abstract

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.

Medical expenditures for devices are increasing along with the ageing of human population and the synthesis of materials such as silicone polymers is on upsurge for manufacturing these devices. The International Organization for Standardization (ISO) emphasizes a battery of tests for preclinical assessment of biocompatibility of medical devices. Genotoxicity assays have become an integral component of these test procedures and it employs a set of in vitro and in vivo experiments to detect mutagens. Hence, this study was performed with an intention to investigate the genotoxic potential of the physiological saline extracts of three medical grade silicone polymer materials by the in vitro chromosomal aberration assay using human peripheral blood lymphocytes. Further, the oxidative stress inducing potential of the material extracts was investigated in vivo in mice liver homogenates using cyclophosphamide as positive control. The investigation revealed that none of the three materials were able to produce marked human lymphocyte chromosomal aberration, suggesting the absence of mutagens. The materials also showed negative results in their oxidative stress inducing potential, which was revealed by the normal levels of lipid peroxidation and unaltered levels of glutathione and its metabolizing enzymes in the mice liver tissue homogenates. It was interesting to observe a significant correlation between the genotoxic and antioxidant parameters investigated. Hence, it is suggested that the estimation of antioxidant status would serve as a better preliminary testing procedure prior to evaluating the genetic and molecular toxicity mechanisms of medical devices and/or materials intended for manufacture of such devices.