Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine

Ghare, Smita; Donde, Hridgandh; Chen, Wei-Yang; Barker, David F.; Gobejishvilli, Leila; McClain, Craig J.; Barve, Shirish; Joshi‐Barve, Swati

doi:10.1016/j.tiv.2016.05.013

Cited by 9 publications

(5 citation statements)

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“…The choice of drugs for immunosuppression and antiretroviral therapy is another key factor. Potential hepatotoxicity must be considered in the selection of HAART regimens to reduce liver-related mortality, such as stavudine (D4T) [ 39 ], azidothymidine (AZT) [ 40 ] or didanosine (ddI) [ 41 ]. All Chinese patients did not receive the above HAART drugs.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China

Tang,

Weng,

Fang

et al. 2024

BMC Infect Dis

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Background Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. Methods We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. Results The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12–39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. Conclusions Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. Trial registration Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.

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Section: Discussionmentioning

confidence: 99%

Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China

Tang,

Weng,

Fang

et al. 2024

BMC Infect Dis

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“…ZDV, SQV, and EFV remain the most commonly used anti‐HIV drugs in third‐world countries. [ 15 ] VACV is the first‐line treatment for HSV. [ 16 ] The sequence of 2019‐nCoV is similar to severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus (MERS‐CoV).…”

Section: Discussionmentioning

confidence: 99%

Antiviral drugs suppress infection of 2019‐nCoV spike pseudotyped virus by interacting with ACE2 protein

Wang

Zhang

et al. 2021

J Biochem & Molecular Tox

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The outbreak of coronavirus disease 2019 (COVID‐19) has induced a large number of deaths worldwide. Angiotensin‐converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019‐nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID‐19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019‐nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the K D value of (4.33 ± 0.09) e −8 , (6.29 ± 1.12) e −6 , (2.37 ± 0.59) e −5 , and (4.85 ± 1.57) e −5 M, respectively. But only ZDV and EFV prevent the 2019‐nCoV spike pseudotyped virus to enter ACE2‐HEK293T cells with an EC 50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019‐nCoV infection of ACE2‐HEK293T cells by interacting with ACE2.

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“…[15,16] In 1987, zidovudine, the first nucleoside drug for blocking the HIV reverse transcription (RT), was born. [17] Subsequently, new drugs such as didanosine and zalcitabine continued to emerge. Although these drugs contributed to a significant inhibitory effect on HIV, they had widespread serious drawbacks such as poor selectivity and HIV susceptibility.…”

Section: Anti-human Immunodeficiency Virus (Hiv) Activitymentioning

confidence: 99%

“…In 1987, zidovudine, the first nucleoside drug for blocking the HIV reverse transcription (RT), was born . Subsequently, new drugs such as didanosine and zalcitabine continued to emerge.…”

Section: Pharmacological Effects and Structure–activity Relationshipsmentioning

confidence: 99%

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure–Activity Relationships

Zhu

Jiang

2018

Molecular Nutrition Food Res

126

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Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, antitumor, anti-inflammation, and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.

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Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine

Cited by 9 publications

References 61 publications

Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China

Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China

Antiviral drugs suppress infection of 2019‐nCoV spike pseudotyped virus by interacting with ACE2 protein

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure–Activity Relationships

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