De novo design based pharmacophore query generation and virtual screening for the discovery of Hsp-47 inhibitors.

Heat shock protein-47 (Hsp-47) is exclusive collagen specific molecular chaperone involved in the maturation, processing and secretion of procollagen. Hsp-47 is consistently upregulated in several fibrotic diseases. Till date there is no potential antifibrotic small molecule drug available and Hsp-47 is known to be potential therapeutic target for fibrotic disorder and drug designing. We used the de novo drug design approach followed by pharmacophore generation and virtual screening to propose Hsp-47 based antifibrotic molecules. We used e-LEAD server for de novo drug design and ZINCPharmer for 3D pharmacophore generation and virtual screening. The virtually screened molecule may inhibit direct recruitment of collagen triple helix to interact with Hsp-47 and act as antifibrotic drug.

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet.

CONTEXT: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties. OBJECTIVE: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity. MATERIALS AND METHODS: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3 ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques. RESULTS: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100 g body weight) of ovary (Gr-I: 54.3 ± 4.2 versus Gr-II: 35.8 ± 1.6; p < 0.001) and uterus (Gr-I: 161.7 ± 24.6 versus Gr-II: 94.44 ± 13.2; p < 0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ(5), 3ß-hydroxysteroid dehydrogenase (Gr-I: 3.41 ± 0.12 versus Gr-II: 2.31 ± 0.09; p < 0.01) and 17ß-hydroxysteroid dehydrogenase (Gr-I: 3.82 ± 0.57 versus Gr-II: 1.24 ± 0.19; p < 0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5 ± 2.06 versus 34.1 ± 2.34; p < 0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10 ± 2.45 versus Gr-II: 29.51 ± 3.44; p < 0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18 ± 0.19 versus Gr-II: 1.33 ± 0.18; p < 0.05). The Gr-III rats were significantly protected from these ill effects of arsenic. DISCUSSION AND CONCLUSION: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.

Zinc and vitamin A can minimise the severity of oral submucous fibrosis.

We report a case of a 24-year-old man who presented with a complaint of reduced mouth opening and a burning sensation. On examination, he was clinically diagnosed with oral submucous fibrosis (OSF). Following routine biopsy and histopathological confirmation of OSF, the patient was supplemented with zinc acetate along with vitamin A and was followed up for 4 months. Following treatment the patient reported increased mouth opening and a reduced burning sensation. Histopathologically re-epithelialisation was evident along with the appearance of normal rete pegs. The data for mouth opening, collagen content and epithelial thickness of six other cases similarly treated are also presented, showing a significant increase in mouth opening and epithelial thickness and decrease in collagen content. We propose the use of zinc acetate and vitamin A for the management of OSF.

In vitro and in vivo reduction of sodium arsenite induced toxicity by aqueous garlic extract.

BACKGROUND: Arsenic is ubiquitous in the environment, and chronic or acute exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. Despite arsenic being a health hazard and a well-documented human carcinogen, a safe, effective and specific preventive or therapeutic measure for treating arsenic induced toxicity still eludes us. OBJECTIVE: This study was undertaken to evaluate the therapeutic efficacy of aqueous garlic (Allium sativum L.) extract (AGE) in terms of normalization of altered biochemical parameters particularly indicative of oxidative stress following sodium arsenite (NaAsO(2)) exposure and depletion of inorganic arsenic burden, in vitro and in vivo. RESULTS: AGE (2mg/ml) co-administered with 10 microM NaAsO(2) attenuated arsenite induced cytotoxicity, reduced intracellular reactive oxygen species (ROS) level in human malignant melanoma cells (A375), human keratinocyte cells (HaCaT) and in cultured human normal dermal fibroblast cells. Moreover, AGE application in NaAsO(2) intoxicated Sprague-Dawley rats resulted in a marked inhibition of tissue lipid peroxide generation; enhanced level of total tissue sulfhydryl groups and glutathione; and also increased the activities of antioxidant enzymes, superoxide dismutase and catalase to near normal. An increase in blood ROS level and myeloperoxidase activity in arsenic-intoxicated rats was effectively prevented by AGE administration. AGE was also able to counter arsenic mediated incongruity in blood hematological variables and glucose level. CONCLUSIONS: The restorative property of AGE was attributed to its antioxidant activity, chelating efficacy, and/or oxidizing capability of trivalent arsenic to its less toxic pentavalent form. Taken together, evidences indicate that AGE can be a potential protective regimen for arsenic mediated toxicity.