Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception

Jain, Ashish; Kumar, Lokesh; Kushwaha, Bhavana; Sharma, Monika; Pandey, Aastha; Verma, Vikas; Sharma, Vikas; Singh, Vishal; Rawat, Tara; Sharma, Vishnu L.; Maikhuri, Jagdamba P.; Gupta, Gopal

doi:10.1093/humrep/det423

Cited by 17 publications

(9 citation statements)

References 33 publications

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“…We took these cells for the present study, because these had been widely used as a representative pair of cancerous and normal cells (for example, Govender et al, 2014;Jain et al, 2014). These cells were handled with commonly used methods and procedures.…”

Section: Methodsmentioning

confidence: 99%

Stiffness of cancer cells measured with an AFM indentation method

Hayashi

Iwata

2015

Journal of the Mechanical Behavior of Biomedical Materials

146

104

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Section: Methodsmentioning

confidence: 99%

Stiffness of cancer cells measured with an AFM indentation method

Hayashi

Iwata

2015

Journal of the Mechanical Behavior of Biomedical Materials

146

104

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“…Previously well characterized immortalized cell lines, originating from normal human vagina (Vk2/E6E7), endocervix (End1/E6E7), and ectocervix (Ect1/E6E7) of the human uterus ( 27 ), were cultured ( 28 ) in antibiotic-free keratinocyte serum-free medium (KSFM), supplemented with 50 μg/ml bovine pituitary extract, 0.1 ng/ml epidermal growth factor (Invitrogen), and 0.4 m m CaCl 2 (Fisher). These cell lines have been established as a physiologically relevant in vitro model for the study of T. vaginalis pathogenesis by multiple investigators ( 9 , 12 , 17 , 29 – 31 ) and have been extensively compared with their primary tissues of origin and with primary organotypic cultures showing no significant differences in responses to T. vaginalis parasites and purified LPG as well as other innate immunity ligands ( 9 , 11 , 13 , 27 , 28 , 32 – 36 ). VEC-100 TM tissues (MatTek, Ashland, MA) were handled as described.…”

Section: Methodsmentioning

confidence: 99%

Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity

Fichorova

Yamamoto

Fashemi

et al. 2016

Journal of Biological Chemistry

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Trichomoniasis is the most common non-viral sexually transmitted infection caused by the vaginotropic extracellular protozoan parasite Trichomonas vaginalis. The infection is recurrent, with no lasting immunity, often asymptomatic, and linked to pregnancy complications and risk of viral infection. The molecular mechanisms of immune evasion by the parasite are poorly understood. We demonstrate that galectin-1 and -3 are expressed by the human cervical and vaginal epithelial cells and act as pathogen-recognition receptors for the ceramide phosphoinositol glycan core (CPI-GC) of the dominant surface protozoan lipophosphoglycan (LPG). We used an in vitro model with siRNA galectin knockdown epithelial clones, recombinant galectins, clinical Trichomonas isolates, and mutant protozoan derivatives to dissect the function of galectin-1 and -3 in the context of Trichomonas infection. Galectin-1 suppressed chemokines that facilitate recruitment of phagocytes, which can eliminate extracellular protozoa (IL-8) or bridge innate to adaptive immunity (MIP-3α and RANTES (regulated on activation normal T cell expressed and secreted)). Silencing galectin-1 increased and adding exogenous galectin-1 suppressed chemokine responses to Trichomonas or CPI-GC/LPG. In contrast, silencing galectin-3 reduced IL-8 response to LPG. Live Trichomonas depleted the extracellular levels of galectin-3. Clinical isolates and mutant Trichomonas CPI-GC that had reduced affinity to galectin-3 but maintained affinity to galectin-1 suppressed chemokine expression. Thus via CPI-GC binding, Trichomonas is capable of regulating galectin bioavailability and function to the benefit of its parasitic survival. These findings suggest novel approaches to control trichomoniasis and warrant further studies of galectin-binding diversity among clinical isolates as a possible source for symptom disparity in parasitic infections.

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“…Although we have not included nonoxynol-9 as a positive control in our in-vivo toxicity study, other authors have done it previously with similar methodology to assess spermicide activity. In rabbits treated with nonoxynol-9 as positive control, erosion of the vaginal epithelial lining, marked leukocyte infiltration, haemorrhage, decreased epithelial cell-height and necrosis of the vaginal epithelium were obtained [31]. …”

Section: Resultsmentioning

confidence: 99%

Hydroxytyrosol

Bedoya

Beltrán

Obregón-Calderón

et al. 2016

Aids

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Objective:To investigate the toxicity and activity against HIV of 5-hydroxytyrosol as a potential microbicide.Design:The anti-HIV-1 activity of 5-hydroxytyrosol, a polyphenolic compound, was tested against wild-type HIV-1 and viral clones resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and integrase inhibitors. In addition to its activity against founder viruses, different viral subtypes and potential synergy with tenofovir disoproxil fumarate, lamivudine and emtricitabine was also tested. 5-Hydroxytyrosol toxicity was evaluated in vivo in rabbit vaginal mucosa.Methods:We have cloned pol gene from drug-resistant HIV-1 isolated from infected patients and env gene from Fiebeg III/IV patients or A, C, D, E, F and G subtypes in the NL4.3-Ren backbone. 5-Hydroxytyrosol anti-HIV-1 activity was evaluated in infections of MT-2, U87-CCR5 or peripheral blood mononuclear cells preactivated with phytohemagglutinin + interleukin-2 with viruses obtained through 293T transfections. Inhibitory concentration 50% and cytotoxic concentration 50% were calculated. Synergy was analysed according to Chou and Talalay method. In-vivo toxicity was evaluated for 14 days in rabbit vaginal mucosa.Results:5-Hydroxytyrosol inhibited HIV-1 infections of recombinant or wild-type viruses in all the target cells tested. Moreover, 5-hydroxytyrosol showed similar inhibitory concentration 50% values for infections with NRTIs, NNRTIs, protease inhibitors and INIs resistant viruses; founder viruses and all the subtypes tested. Combination of 5-hydroxytyrosol with tenofovir was found to be synergistic, whereas it was additive with lamivudine and emtricitabine. In-vivo toxicity of 5-hydroxytyrosol was very low even at the highest tested doses.Conclusion:5-Hydroxytyrosol displayed a broad anti-HIV-1 activity in different cells systems in the absent of in-vivo toxicity, therefore supporting its candidacy as a potential new class of microbicides.

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Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception

Abstract: The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

Cited by 17 publications

References 33 publications

Stiffness of cancer cells measured with an AFM indentation method

Stiffness of cancer cells measured with an AFM indentation method

Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity

Hydroxytyrosol

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