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Molecules (Basel, Switzerland) Apr 2024Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether...
Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.
Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.
Topics: Cisplatin; Papaverine; Oxidative Stress; Animals; Rats; Inflammation; Humans; Kidney; Male; Apoptosis; Antineoplastic Agents; Protective Agents; Antioxidants; Cytokines; Computer Simulation; Biomarkers
PubMed: 38731418
DOI: 10.3390/molecules29091927 -
Journal of Virology Feb 2020Influenza viruses are highly infectious and are the leading cause of human respiratory diseases and may trigger severe epidemics and occasional pandemics. Although...
Influenza viruses are highly infectious and are the leading cause of human respiratory diseases and may trigger severe epidemics and occasional pandemics. Although antiviral drugs against influenza viruses have been developed, there is an urgent need to design new strategies to develop influenza virus inhibitors due to the increasing resistance of viruses toward currently available drugs. In this study, we examined the antiviral activity of natural compounds against the following influenza virus strains: A/WSN/33 (H1N1), A/Udorn/72 (H3N2), and B/Lee/40. Papaverine (a nonnarcotic alkaloid that has been used for the treatment of heart disease, impotency, and psychosis) was found to be an effective inhibitor of multiple strains of influenza virus. Kinetic studies demonstrated that papaverine inhibited influenza virus infection at a late stage in the virus life cycle. An alteration in influenza virus morphology and viral ribonucleoprotein (vRNP) localization was observed as an effect of papaverine treatment. Papaverine is a well-known phosphodiesterase inhibitor and also modifies the mitogen-activated protein kinase (MAPK) pathway by downregulating the phosphorylation of MEK and extracellular signal-regulated kinase (ERK). Thus, the modulation of host cell signaling pathways by papaverine may be associated with the nuclear retention of vRNPs and the reduction of influenza virus titers. Interestingly, papaverine also inhibited paramyxoviruses parainfluenza virus 5 (PIV5), human parainfluenza virus 3 (HPIV3), and respiratory syncytial virus (RSV) infections. We propose that papaverine can be a potential candidate to be used as an antiviral agent against a broad range of influenza viruses and paramyxoviruses. Influenza viruses are important human pathogens that are the causative agents of epidemics and pandemics. Despite the availability of an annual vaccine, a large number of cases occur every year globally. Here, we report that papaverine, a vasodilator, shows inhibitory action against various strains of influenza virus as well as the paramyxoviruses PIV5, HPIV3, and RSV. A significant effect of papaverine on the influenza virus morphology was observed. Papaverine treatment of influenza-virus-infected cells resulted in the inhibition of virus at a later time in the virus life cycle through the suppression of nuclear export of vRNP and also interfered with the host cellular cAMP and MEK/ERK cascade pathways. This study explores the use of papaverine as an effective inhibitor of both influenza viruses as well as paramyxoviruses.
Topics: Animals; Antiviral Agents; Dogs; Drug Evaluation, Preclinical; Drug Repositioning; HEK293 Cells; Humans; MAP Kinase Signaling System; Madin Darby Canine Kidney Cells; Orthomyxoviridae; Orthomyxoviridae Infections; Papaverine; Paramyxoviridae Infections; Paramyxovirinae
PubMed: 31896588
DOI: 10.1128/JVI.01888-19 -
Asian Journal of Andrology 2015Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function... (Review)
Review
Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation.
Topics: Adenocarcinoma; Adrenergic alpha-Antagonists; Alprostadil; Equipment and Supplies; Erectile Dysfunction; Humans; Injections; Male; Papaverine; Phentolamine; Phosphodiesterase 5 Inhibitors; Prostatectomy; Prostatic Neoplasms; Radiotherapy; Suppositories; Ultrasonic Therapy; Vasodilator Agents; Vibration
PubMed: 25851656
DOI: 10.4103/1008-682X.150838 -
Advanced Pharmaceutical Bulletin Jul 2020Wound-healing dipyridamole- and papaverine-based aerosols (D1/D2) as activators of the accumulation of cyclic adenosine monophosphate are promising drugs that can...
Wound-healing dipyridamole- and papaverine-based aerosols (D1/D2) as activators of the accumulation of cyclic adenosine monophosphate are promising drugs that can accelerate wound healing in wound processes of various origins. 128 rats were used in the study, including 38 in a pharmacological experiment on a model of stencil wounds and 90 in an experiment that studied the effect of spray on the number of CD34 cells in the blood of rats with chemically induced immunodeficiency. Immunodeficiency was caused by the fivefold administration of cyclophosphamide and prednisone. The expression level of CD34 was determined using flow cytofluorimeter. Dipyridamole- and papaverine-based aerosols of two compositions (with and without ascorbic acid) have pronounced reparative properties, significantly accelerating epithelialization and healing of stencil wounds in rats. In terms of this type of action, they are somewhat superior to dexpanthenol. Dipyridamole- and papaverine-based aerosols have the ability to produce beneficial effect on the entire body's immune system by stimulating the division of pluripotent CD34 cells. The combined effect of papaverine and dipyridamole on tissues leads to selective stimulation of the division of pluripotent cells in the wound, and contributes to a six-fold acceleration of restoration of the animal's immune system after induced immunodeficiency. Topical application of D1/D2 aerosol samples on the skin of rats contributed to a statistically significant acceleration of regeneration processes. In terms of the appearance of granulations and epithelialization of wounds, D1/D2 aerosols were superior to dexpanthenol ointment.
PubMed: 32665909
DOI: 10.34172/apb.2020.059 -
Anesthesia, Essays and Researches 2017Radial artery cannulation is a skillful procedure. An experienced anesthesiologist might also face difficulty in cannulating a feeble radial pulse.
BACKGROUND
Radial artery cannulation is a skillful procedure. An experienced anesthesiologist might also face difficulty in cannulating a feeble radial pulse.
AIM
The purpose of the study was to determine whether periradial subcutaneous administration of papaverine results in effective vasodilation and improvement in the palpability score of radial artery.
SETTINGS AND DESIGN
Prospective, double-blinded trial.
METHODOLOGY
Thirty patients undergoing elective cardiac surgery were enrolled in the study. 30 mg of papaverine with 1 ml of 2% lignocaine and 3 ml of normal saline were injected subcutaneously 1-2 cm proximal to styloid process of the radius. Radial artery diameter before and after 20 min of injection papaverine was measured using ultrasonography. The palpability of the radial pulse was also determined before the injection of papaverine and 20 min later. Patients were monitored for hemodynamics and any complications were noted.
STATISTICAL ANALYSIS USED
Student's -test for paired data.
RESULTS
Radial artery diameter increased significantly ( < 0.0001), and the pulse palpability score also showed statistically significant improvement ( < 0.0001) after periradial subcutaneous administration of papaverine. There was no statistically significant difference in heart rate, mean arterial blood pressure before and after papaverine injection. No complications were noted in 24 h of follow-up.
CONCLUSION
Periradial subcutaneous administration of papaverine significantly increased the radial artery diameter and pulse palpability score, which had an impact on ease of radial artery cannulation essential for hemodynamic monitoring in cardiac surgical patients.
PubMed: 28298790
DOI: 10.4103/0259-1162.194579 -
Noise & Health 2018Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to...
INTRODUCTION
Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation.
MATERIALS AND METHODS
Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study. We investigated the histopathologic effects of cellular apoptosis on inner hair cells (IHCs) and outer hair cells (OHCs) and compared the distortion product otoacoustic emissions (DPOAEs) thresholds among the groups.
RESULTS AND DISCUSSION
On the 3 and 7 days, DPOAE thresholds at 8 kHz were significantly higher both in papaverine and piracetam groups compared with the control group (P = 0.004 for 3 day, P = 0.016 and P = 0.028 for 7 day, respectively). On the 14 day, piracetam group had significantly higher mean thresholds at 8 kHz (P = 0.029); however, papaverine group had similar mean thresholds compared to the control group (P = 0.200). On the 3 and 7 days following acoustic trauma, both IHC and OHC loss were significantly lower in both papaverine and piracetam groups. On the 7 day, the mean amount of apoptotic IHCs and OHCs identified using Caspase-3 method were significantly lower in both groups, but the mean amount identified using terminal deoxynucleotidyl transferase dUTP nick end labeling method were similar in both groups compared to the control group.
CONCLUSION
We demonstrated the effects of papaverine and piracetam on the recovery of cochlear damage due to acoustic trauma on experimental animals using histopathologic and electrophysiologic examinations.
Topics: Animals; Apoptosis; Electrophysiology; Hair Cells, Auditory, Inner; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; Injections, Intraperitoneal; Male; Neuroprotective Agents; Otoacoustic Emissions, Spontaneous; Papaverine; Piracetam; Rats, Wistar
PubMed: 29676295
DOI: 10.4103/nah.NAH_31_17 -
Revista Da Associacao Medica Brasileira... Sep 2020The vascular evaluation of the erectile function through Color Duplex-Doppler Ultrasound (CDDU) of the penis can benefit the therapeutic decision-making process.... (Review)
Review
INTRODUCTION
The vascular evaluation of the erectile function through Color Duplex-Doppler Ultrasound (CDDU) of the penis can benefit the therapeutic decision-making process. Unfortunately, there is no standard procedure for CDDU conduction, a fact that results in high result-interpretation variability.
OBJECTIVE
The aims of this review are to promote greater standardization during CDDU of the penis and discuss the fundamental principles for its accurate conduction.
METHODS
CDDU is initially conducted with the penis in the flaccid state; the whole penis must be assessed (images at B mode) with a high-frequency linear transducer (7.5-18 MHz). Intracavernous injection of vasodilating agents (prostaglandin E1, papaverine, phentolamine) is performed to induce a rigid erection. Serial measurements at different times should be taken during the CDDU session and penile rigidity must be assessed in each evaluation.
RESULTS
It is important to monitor the erection response after the vasoactive agent (hardness scale), and scanning during the best-quality erection should be contemplated. Manual self-stimulation, audiovisual sexual stimulation (AVSS), and vasoactive agent re-dosing protocols must be taken into account to reduce the influence of psychogenic factors and to help the patient to get the hardest erection possible. Such measurements contribute to the maximal relaxation of the erectile tissue, so the hemodynamic parameters are not underestimated.
CONCLUSIONS
CDDU is a relevant specialized tool to assess patients with erectile dysfunction; therefore, this guideline will help to standardize and establish uniformity in its conduction and interpretation, taking into consideration the complexity and heterogeneity of CDDU evaluations of the penis.
Topics: Erectile Dysfunction; Hemodynamics; Humans; Male; Penile Erection; Penis; Ultrasonography, Doppler, Color
PubMed: 33027442
DOI: 10.1590/1806-9282.66.9.1180 -
BMC Research Notes Sep 2021Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In...
OBJECTIVE
Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In this study, both species were evaluated for their alkaloid content and antimicrobial activities.
RESULTS
Alkaloids were extracted and isolated by preparative thin-layer chromatography (TLC). Identification was carried out by comparing spectral data (UV and H-NMR) and TLC Rf values with those of authentic samples. Two alkaloids, proapaorphine-type mecambrine and aporphine-type roemerine were isolated from P. decaisnei. Two benzylisoquinoline type alkaloids papaverine (major alkaloid) and palaudine as well as aporphine-type N-methylasimilobine have been obtained in P. glaucum. Both P. glaucum and P. decaisnei extracts revealed strong antimicrobial activity on Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. Collectively these results indicate that P. glaucum and P. decaisnei are promising sources of alkaloids that could further be investigated for medicinal purposes.
Topics: Alkaloids; Anti-Infective Agents; Chromatography, Thin Layer; Papaver; Plant Extracts
PubMed: 34496958
DOI: 10.1186/s13104-021-05762-x -
The Analyst Oct 2018A method has been developed for extracting poppy alkaloids from oily matrices, specifically lipid residues associated with archaeological ceramics. The protocol has been...
A method has been developed for extracting poppy alkaloids from oily matrices, specifically lipid residues associated with archaeological ceramics. The protocol has been applied to fresh and artificially aged poppyseed oil and to residue from a Late Bronze Age Cypriot juglet in the collections of the British Museum. The juglet is of a type that has been linked with ancient trade in opium due to its poppy-head shape and wide distribution; it is a rare example of an intact vessel with contents sealed inside. Bulk analysis of the residue by GC-EI-MS and pyGC-EI-MS indicated a degraded plant oil and possible presence of papaverine. Analysis of the alkaloid extracts by HPLC-ESI-MS using both triple quadrupole and FTICR mass spectrometers detected the five primary opium alkaloids in fresh poppyseed oil and papaverine in most of the aged samples. Papaverine and thebaine were detected in the juglet residue, providing the first rigorous chemical evidence to support a link between this vessel type and opium, or at least poppies. The association of opium with oil raises new questions about the ancient purpose of the commodities within these vessels, and the low levels (ng g-1) of opiates detected in this unusually well-preserved residue shed doubt on the scope for their detection in more fragmentary ceramic remains (potsherds). Papaverine was found to exhibit challenging carryover behaviour in all the analytical methods used in this study. The phenomenon has not been reported before and should be considered in future analyses of this analyte in all application areas.
Topics: Archaeology; Ceramics; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Limit of Detection; Opium; Papaver; Papaverine; Plant Oils; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Thebaine
PubMed: 30280166
DOI: 10.1039/c8an01040d -
Indian Pediatrics Oct 2015
Topics: Abdominal Pain; Chronic Pain; Female; Gastrointestinal Diseases; Humans; Male; Papaverine
PubMed: 26499005
DOI: No ID Found