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Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs
Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protecti...
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| Published in: | Scientific reports 2019-06, Vol.9 (1), p.8531-8531, Article 8531 |
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| creator | Gogulamudi, Venkateswara Reddy Dubey, Mohan Lal Kaul, Deepak Hubert, Donfack Jean Kandimalla, Ramesh Sehgal, Rakesh |
| description | Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D
3
, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against
L
.
donovani
infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D
3
/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D
3
/RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of
L
.
donovani
by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D
3
and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis. |
| doi_str_mv | 10.1038/s41598-019-44630-4 |
| format | article |
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3
, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against
L
.
donovani
infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D
3
/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D
3
/RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of
L
.
donovani
by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D
3
and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-44630-4</identifier><identifier>PMID: 31189939</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/21 ; 13/31 ; 13/51 ; 14 ; 14/63 ; 631/154/555 ; 631/250/255 ; 64/60 ; Adjuvants, Immunologic - pharmacology ; Animals ; Antiprotozoal Agents - pharmacology ; Chenodeoxycholic acid ; Chenodeoxycholic Acid - pharmacology ; Cholecalciferol - pharmacology ; Cytokines - immunology ; Humanities and Social Sciences ; Immune response ; Immunomodulation ; Immunostimulation ; Immunosuppression ; Immunosuppressive agents ; Interleukin 1 ; Interleukin 4 ; Interleukin 5 ; Leishmania donovani - immunology ; Leishmaniasis, Visceral - drug therapy ; Leishmaniasis, Visceral - immunology ; Leishmaniasis, Visceral - pathology ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; multidisciplinary ; Parasites ; Parasitic diseases ; Retinoic acid ; Science ; Science (multidisciplinary) ; Spleen ; Terpenes ; Th1 Cells - immunology ; Th1 Cells - pathology ; Toxicity ; Tumor necrosis factor-α ; Vector-borne diseases ; Visceral leishmaniasis ; Vitamin A ; Vitamin A - pharmacology ; Vitamin D ; Vitamin D3 ; Vitamins ; γ-Interferon</subject><ispartof>Scientific reports, 2019-06, Vol.9 (1), p.8531-8531, Article 8531</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-22bb923b428ef98c4d187db616d9a73bd8cd62a5844a21ee3cda93ea7ff98c573</citedby><cites>FETCH-LOGICAL-c511t-22bb923b428ef98c4d187db616d9a73bd8cd62a5844a21ee3cda93ea7ff98c573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2239169273/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2239169273?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31189939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gogulamudi, Venkateswara Reddy</creatorcontrib><creatorcontrib>Dubey, Mohan Lal</creatorcontrib><creatorcontrib>Kaul, Deepak</creatorcontrib><creatorcontrib>Hubert, Donfack Jean</creatorcontrib><creatorcontrib>Kandimalla, Ramesh</creatorcontrib><creatorcontrib>Sehgal, Rakesh</creatorcontrib><title>Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D
3
, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against
L
.
donovani
infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D
3
/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D
3
/RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of
L
.
donovani
by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D
3
and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis.</description><subject>13</subject><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>14</subject><subject>14/63</subject><subject>631/154/555</subject><subject>631/250/255</subject><subject>64/60</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Animals</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Chenodeoxycholic acid</subject><subject>Chenodeoxycholic Acid - pharmacology</subject><subject>Cholecalciferol - pharmacology</subject><subject>Cytokines - immunology</subject><subject>Humanities and Social Sciences</subject><subject>Immune response</subject><subject>Immunomodulation</subject><subject>Immunostimulation</subject><subject>Immunosuppression</subject><subject>Immunosuppressive agents</subject><subject>Interleukin 1</subject><subject>Interleukin 4</subject><subject>Interleukin 5</subject><subject>Leishmania donovani - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gogulamudi, Venkateswara Reddy</au><au>Dubey, Mohan Lal</au><au>Kaul, Deepak</au><au>Hubert, Donfack Jean</au><au>Kandimalla, Ramesh</au><au>Sehgal, Rakesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-06-12</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>8531</spage><epage>8531</epage><pages>8531-8531</pages><artnum>8531</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D
3
, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against
L
.
donovani
infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D
3
/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D
3
/RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of
L
.
donovani
by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D
3
and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31189939</pmid><doi>10.1038/s41598-019-44630-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2019-06, Vol.9 (1), p.8531-8531, Article 8531 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6562038 |
| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 13 13/21 13/31 13/51 14 14/63 631/154/555 631/250/255 64/60 Adjuvants, Immunologic - pharmacology Animals Antiprotozoal Agents - pharmacology Chenodeoxycholic acid Chenodeoxycholic Acid - pharmacology Cholecalciferol - pharmacology Cytokines - immunology Humanities and Social Sciences Immune response Immunomodulation Immunostimulation Immunosuppression Immunosuppressive agents Interleukin 1 Interleukin 4 Interleukin 5 Leishmania donovani - immunology Leishmaniasis, Visceral - drug therapy Leishmaniasis, Visceral - immunology Leishmaniasis, Visceral - pathology Lymphocytes T Mice Mice, Inbred BALB C multidisciplinary Parasites Parasitic diseases Retinoic acid Science Science (multidisciplinary) Spleen Terpenes Th1 Cells - immunology Th1 Cells - pathology Toxicity Tumor necrosis factor-α Vector-borne diseases Visceral leishmaniasis Vitamin A Vitamin A - pharmacology Vitamin D Vitamin D3 Vitamins γ-Interferon |
| title | Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs |
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