Browsing by Author "Divya Dubey"

Now showing 1 - 5 of 5

Ambient UV-B exposure reduces the binding of ofloxacin with bacterial DNA gyrase and induces DNA damage mediated apoptosis
(Elsevier Ltd, 2016) Jyoti Singh; Ashish Dwivedi; Syed Faiz Mujtaba; Krishna P. Singh; Manish Kumar Pal; Deepti Chopra; Shruti Goyal; Ajeet K. Srivastav; Divya Dubey; Shailendra K. Gupta; Chandana Haldar; Ratan Singh Ray
Ofloxacin (OFLX) is a broad spectrum antibiotic, which generates photo-products under sunlight exposure. Previous studies have failed to explain the attenuated anti-bacterial activity of OFLX. The study was extended to explore the unknown molecular mechanism of photogenotoxicity on human skin cell line (HaCaT) under environmental UV-B irradiation. Photochemically OFLX generates ROS and caused 2′-dGuO photodegradation. We have addressed the binding affinity of OFLX and its photo-products against DNA gyrase. Significant free radical generation such as 1O2, O2•- and •OH reduces antioxidants and demonstrated the ROS mediated OFLX phototoxicity. However, the formation of micronuclei and CPDs showed photogenotoxic potential of OFLX. OFLX induced cell cycle arrest in sub-G1 peak. OFLX triggers apoptosis via permeabilization of mitochondrial membrane with the downregulation of anti-apoptotic Bcl-2 and caspase-3 whereas, upregulation of pro-apoptotic Bax and Cyto-C proteins. Our study illustrated that binding affinity of OFLX photo-products with DNA gyrase was mainly responsible for the attenuated antimicrobial activity. It was proved through molecular docking study. Thus, study suggests that sunlight exposure should avoid by drug users especially during peak hours for their safety from photosensitivity. Clinicians may guide patients regarding the safer use of photosensitive drugs during treatment. © 2016 Published by Elsevier Ltd.
Corrigendum to “PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure” [Int. J. Pharm. 541 (2018) 173–187] (International Journal of Pharmaceutics (2018) 541(1–2) (173–187), (S0378517318301091) (10.1016/j.ijpharm.2018.02.028))
(Elsevier B.V., 2018) Jyoti Singh; Ashish Dwivedi; Lipika Ray; Deepti Chopra; Divya Dubey; Ajeet K. Srivastva; Smita Kumari; Randhir Kumar Yadav; Saroj Kumar Amar; Chandana Haldar; Ratan Singh Ray
The authors regret that mistakes related to image duplication, quality and labeling were found in Fig. 7b Fig. 9 Fig. 10 a. The corrected images are now provided as Figs. 7b, 9c, d and 10a. These mistakes do not change the scientific conclusions of the article in any way. The authors would like to apologise for any inconvenience caused. © 2018 Elsevier B.V.
Corrigendum to “PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure” [Int. J. Pharm. 541 (2018) 173–187](S0378517318301091)(10.1016/j.ijpharm.2018.02.028)
(Elsevier B.V., 2019) Jyoti Singh; Ashish Dwivedi; Lipika Ray; Deepti Chopra; Divya Dubey; Ajeet K. Srivastva; Smita Kumari; Randhir Kumar Yadav; Saroj Kumar Amar; Chandana Haldar; Ratan Singh Ray
The authors regret to inform that there were inadvertent errors in some figures. The corrected images are given below. These corrections are not affecting the results and conclusion of the manuscript. Hence, the text in the original article remains unchanged. The corrected Fig. 8 is as follows: The corrected Fig. 12 is as follows: The authors would like to apologise for any inconvenience caused. © 2019 Elsevier B.V.
PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure
(Elsevier B.V., 2018) Jyoti Singh; Ashish Dwivedi; Lipika Ray; Deepti Chopra; Divya Dubey; Ajeet K. Srivastva; Smita Kumari; Randhir Kumar Yadav; Saroj Kumar Amar; Chandana Haldar; Ratan Singh Ray
Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA gyrase enzyme activity. However, photodegradation in the presence of UVA limits its antibacterial activity and induces phototoxicity. Thus, to encounter this problem, we have developed poly d,l-lactic-co-glycolic acid (PLGA) loaded SPFX nanoparticles. Here, we have performed a comparative antibacterial activity of SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity assay. Under environmental UVA exposure, photoexcited SPFX significantly generates ROS, DNA damage and mitochondrial mediated cell death in comparison to PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA, bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via alteration in membrane integrity of mitochondria and lysosome in comparison to PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of pro-apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis. Our finding suggests that controlled release of SPFX from PLGA-SPFX-NPs can reduce its side effects and enhance its antibacterial activity. Thus, nanotization of fluoroquinolones will be a significant step to reduce the problem of resistance and phototoxicity of this group. © 2018 Elsevier B.V.
Under ambient UVA exposure, pefloxacin exhibits both immunomodulatory and genotoxic effects via multiple mechanisms
(Elsevier B.V., 2018) Jyoti Singh; Ajeet K. Srivastva; Payal Mandal; Sonam Chandra; Divya Dubey; Ashish Dwivedi; Deepti Chopra; Anurag Tripathi; Ratan Singh Ray
Pefloxacin (PFLX) is an antibiotic, which shows broad spectrum antimicrobial activities. It is an important derivative of fluoroquinolones (FLQs) group. Ultraviolet radiation (200–400 nm) causes major problem for living being which comes at the earth surface naturally through sunlight and increasing regularly due to ozone depletion. PFLX was photodegraded in 5 h and forms photoproduct under UVA exposure. At the non photocytotoxic dose PFLX, shows reduced phagocytosis activity, NO (nitric oxide) production, large vacuole formation and down regulated IL-6, TNF-α and IL-1 in BALB/c macrophages at both genes and proteins levels. At higher doses (photocytotoxic doses), PFLX induced a concentration dependent decrease in cell viability of human keratinocyte cell line (HaCaT) and peritoneal macrophages of BALB/c mice. Our molecular docking suggests that PFLX binds only to the cleaved DNA in the DNA-human TOP2A complex. Topoisomerase assay confirmed that PFLX inhibits human topoisomerase by forming an adduct with DNA. Photosensitized PFLX also caused intracellular ROS mediated DNA damage and formation of micronuclei and cyclobutane pyrimidine dimers (CPDs). Increase intracellular ROS leads to apoptosis which was proved through lysosomal destabilization and reduced mitochondrial membrane potential (MMP). Our present study shows that ambient UVA exposure in the presence of PFLX caused immunomodulatory as well as photogenotoxic effects. Therefore, patients under PFLX drug treatment should avoid sunlight exposure, especially during peak hours for their photosafety. © 2017