Effects of ω-hydroxylase product on distal human pulmonary arteries

2008 ◽  
Vol 294 (3) ◽  
pp. H1435-H1443 ◽  
Author(s):  
Caroline Morin ◽  
Christelle Guibert ◽  
Marco Sirois ◽  
Vincent Echave ◽  
Marcio M. Gomes ◽  
...  
Keyword(s):  
Pulmonary Arteries ◽  
Rho Kinase ◽  
Dependent Manner ◽  
Response Curves ◽  
Inhibitory Protein ◽  
Concentration Dependent Manner ◽  
Intracellular Process ◽  
Free Arachidonic Acid ◽  
Kinase Pathway

The aim of the present study was to provide a mechanistic insight into how 20-hydroxyeicosatetraenoic acid (20-HETE) relaxes distal human pulmonary arteries (HPAs). This compound is produced by ω-hydroxylase from free arachidonic acid. Tension measurements, performed on either fresh or 1 day-cultured pulmonary arteries, revealed that the contractile responses to 1 μM 5-hydroxytryptamine were largely relaxed by 20-HETE in a concentration-dependent manner (0.01–10 μM). Iberiotoxin pretreatments (10 nM) partially decreased 20-HETE-induced relaxations. However, 10 μM indomethacin and 3 μM SC-560 pretreatments significantly reduced the relaxations to 20-HETE in these tissues. The relaxing responses induced by the eicosanoid were likely related to a reduced Ca2+ sensitivity of the myofilaments since free Ca2+ concentration ([Ca2+])-response curves performed on β-escin-permeabilized cultured explants were shifted toward higher [Ca2+]. 20-HETE also abolished the tonic responses induced by phorbol-ester-dibutyrate (a PKC-sensitizing agent). Western blot analyses, using two specific primary antibodies against the PKC-potentiated inhibitory protein CPI-17 and its PKC-dependent phosphorylated isoform pCPI-17, confirmed that 20-HETE interferes with this intracellular process. We also investigated the effect of 20-HETE on the activation of Rho-kinase pathway-induced Ca2+ sensitivity. The data demonstrated that 20-HETE decreased U-46619-induced Ca2+ sensitivity on arteries. Hence, this observation was correlated with an increased staining of p116Rip, a RhoA-binding protein. Together, these results strongly suggest that the 20-hydroxyarachidonic acid derivative is a potent modulator of tone in HPAs in vitro.

Sevoflurane Inhibits Guanosine 5′-[γ-thio]triphosphate–stimulated, Rho/Rho-kinase–mediated Contraction of Isolated Rat Aortic Smooth Muscle

2003 ◽  
Vol 99 (3) ◽  
pp. 646-651 ◽  
Author(s):  
Jingui Yu ◽  
Koji Ogawa ◽  
Yasuyuki Tokinaga ◽  
Yoshio Hatano
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Isometric Force ◽  
Rho Kinase ◽  
Force Transducer ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aortic Smooth Muscle ◽  
Gamma S ◽  
Kinase Pathway

Background The Rho/Rho-kinase signaling pathway plays an important role in mediating Ca2+ sensitization of vascular smooth muscle. The effect of anesthetics on Rho/Rho-kinase-mediated vasoconstriction has not been determined to date. This study is designed to examine the possible inhibitory effects of sevoflurane on the Rho/Rho-kinase pathway by measuring guanosine 5'-[gamma-thio]triphosphate (GTP gamma S)-stimulated contraction and translocation of RhoA (one of the three Rho subtypes) and Rock-2 (one of the two Rho-kinase subtypes) from the cytosol to the membrane in rat aortic smooth muscle. Methods GTP gamma S-induced contraction of rat aortic endothelium-denuded rings was measured using an isometric force transducer, and GTP gamma S-stimulated membrane translocation of RhoA and Rock-2 in smooth muscle cells was detected with Western blotting in the presence and absence of sevoflurane. Results GTP gamma S (10(-4) m) induced a sustained contraction, which was significantly inhibited by the Rho-kinase inhibitor, Y27632 (3 x 10(-6) m). Before treatment with GTP gamma S, RhoA and Rock-2 were detected primarily in the cytosolic fraction. GTP gamma S (10(-4) m) stimulated the translocation of RhoA and Rock-2 from the cytosol to the membrane, which was sustained for more than 60 min. Sevoflurane (1.7, 3.4, and 5.1%) concentration dependently inhibited the GTP gamma S-induced constriction of rat aortic smooth muscle with a reduction of constriction of 52-75% (P < 0.01, n = 8), and attenuated the translocation of RhoA and Rock-2 by 31-66% and 34-78%, respectively (P < 0.05-0.01, respectively; n = 4). Conclusion The current findings show that sevoflurane depresses the GTP gamma S-stimulated contraction and translocation of both Rho and Rho-kinase from the cytosol in a concentration-dependent manner, indicating that sevoflurane is able to inhibit vasoconstriction mediated by the Rho/Rho-kinase pathway in rat aortic smooth muscle.

Effects of Rho kinase inhibition on cerebral artery myogenic tone and reactivity

2005 ◽  
Vol 98 (5) ◽  
pp. 1940-1948 ◽  
Author(s):  
Natalia I. Gokina ◽  
Kristen M. Park ◽  
Keara McElroy-Yaggy ◽  
George Osol
Keyword(s):  
Smooth Muscle ◽  
Cerebral Artery ◽  
Rho Kinase ◽  
Oscillatory Activity ◽  
Comparable Efficacy ◽  
Myogenic Tone ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Kinase Inhibition ◽  
Kinase Pathway

Several recent studies have implicated the RhoA-Rho kinase pathway in arterial myogenic behavior. The goal of this study was to determine the effects of Rho kinase inhibition (Y-27632) on cerebral artery calcium and diameter responses as a function of transmural pressure. Excised segments of rat posterior cerebral arteries (100–200 μm) were cannulated and pressurized in an arteriograph at 37°C. Increasing pressure from 10 to 60 mmHg triggered an elevation of cytosolic calcium concentration ([Ca2+]i) from 113 ± 9 to 199 ± 12 nM and development of myogenic tone. Further elevation of pressure to 120 mmHg induced only a minor additional increase in [Ca2+]i and constriction. Y-27632 (0.3–10 μM) inhibited myogenic tone in a concentration-dependent manner at 60 and 120 mmHg with comparable efficacy; conversely, sensitivity was decreased at 120 vs. 60 mmHg (50% inhibitory concentration: 2.5 ± 0.3 vs. 1.4 ± 0.1 μM; P < 0.05). Dilation was accompanied by further increases in [Ca2+]i and an enhancement of Ca2+ oscillatory activity. Y-27632 also effectively dilated the vessels permeabilized with α-toxin in a concentration-dependent manner. However, dilator effects of Y-27632 at low concentrations were larger at 60 vs. 100 mmHg. In summary, the results support a significant role for RhoA-Rho kinase pathway in cerebral artery mechanotransduction of pressure into sustained vasoconstriction (myogenic tone and reactivity) via mechanisms that augment smooth muscle calcium sensitivity. Potential downstream events may involve inhibition of myosin phosphatase and/or stimulation of actin polymerization, both of which are associated with increased smooth muscle force production.

In vitro myometrial inhibition by the partitioned aqueous fraction of Anthocleista djalonensis leaves

2010 ◽  
Vol 88 (9) ◽  
pp. 880-887
Author(s):  
Enitome Evi Bafor ◽  
Lucky Osaro Okunrobo
Keyword(s):  
Uterine Contraction ◽  
Calcium Influx ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Aqueous Fraction ◽  
Uterine Contractions ◽  
Β Adrenergic Receptors

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration–response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration–response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.

Neural and myogenic effects of leukotrienes C4, D4, and E4 on canine bronchial smooth muscle

1994 ◽  
Vol 266 (4) ◽  
pp. L414-L425 ◽  
Author(s):  
A. Abela ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Contractile Activity ◽  
Neuromuscular Control ◽  
Dependent Manner ◽  
Gamma Glutamyl Transpeptidase ◽  
Response Curves ◽  
Bronchial Smooth Muscle ◽  
Concentration Dependent Manner

The leukotrienes (LTs), referred to as the slow-reacting substance of anaphylaxis (SRS-A), are reported to have little or no activity in the canine airway. The objective of this study was to determine whether LTC4, LTD4, and LTE4 (10(-10)-10(-7) M) play a role in neuromuscular control of third- to fifth-order canine bronchi. In the presence of 1 microM indomethacin (Indo), canine bronchial smooth muscle contracted and was depolarized in a concentration-dependent manner by LTC4 or LTD4 but not by LTE4. LTC4 and LTD4 concentration-response curves were not significantly affected when conducted in the presence of any of the following: 10(-7) M propranolol (beta-adrenoceptor antagonist), 10(-6) M chlorpheniramine (H1-receptor antagonist), 10(-6) M ketanserin (nonselective 5-hydroxytryptamine receptor antagonist), 10(-7) M atropine (muscarinic receptor antagonist), and 10(-6) M tetrodotoxin (sodium channel blocker). LTC4 and LTD4 also potentiated electrical field-stimulated (EFS) excitatory junction potentials (EJPs), suggesting a possible prejunctional enhancement of acetylcholine release. In the absence of Indo, no postjunctional responses to LTC4 and LTD4 occurred. Endogenous prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha (a stable metabolite of PGI2) levels from canine bronchi were significantly reduced by Indo. In the presence of Indo, addition of > or = 10(-8) M of PGE2 suppressed contractions to LTC4 and LTD4. These data suggest that the decrease in PGE2 and PGI2 production by Indo is sufficient to unmask the excitatory postjunctional actions of LTC4 and LTD4 on bronchial smooth muscle. Serine borate (45 mM; an inhibitor of gamma-glutamyl transpeptidase, which prevents the conversion of LTC4 to LTD4) increased selectively the contractile activity of LTC4. L-Cysteine (3 mM; an inhibitor of an aminopeptidase, which prevents the conversion of LTD4 to LTE4) enhanced the contractile responses to LTD4. Serine borate increased the amplitude and duration of EFS contractions and potentiated the amplitude of EFS EJPs; the last effects were prevented by nordihydroguaiaretic acid. These and other studies suggest that LTs are synthesized by canine bronchi and have receptors on canine bronchial smooth muscle but that contractions to LTC4 and LTD4 in the canine airway are usually not observed because of the presence of inhibitory prostanoids (PGE2 and PGI2). We suggest that decreases in PGE2 and PGI2 in models of airway disease in combination with increases in LTC4, LTD4, and thromboxane A2 may contribute to airway hyperresponsiveness in vitro.

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow

1992 ◽  
Vol 70 (10) ◽  
pp. 1336-1341 ◽  
Author(s):  
Karen Harrington ◽  
Arieh Bomzon ◽  
Keith A. Sharkey ◽  
Joseph S. Davison ◽  
Eldon A. Shaffer
Keyword(s):  
Guinea Pig ◽  
Circular Muscle ◽  
Sphincter Of Oddi ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Response Curves ◽  
Gallbladder Contraction ◽  
Concentration Dependent Manner ◽  
Cholinergic Mechanism

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration–response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10−6 M) or tetrodotoxin (10−6 M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10−3 M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves. Duodenal delivery of bile is expedited by CCK, which induces gallbladder contraction at low, near-physiological levels without stimulating the sphincter. Under other conditions, sphincter of Oddi relaxation may facilitate transsphincteric flow. In contrast, increased cholinergic tone may help prevent duodenal reflux into the biliary system.Key words: cholecystokinin, bethanechol, enteric nervous system, gallbladder function, sphincter of Oddi.

scholarly journals Acute Effects of Vardenafil on Pulmonary Artery Responsiveness in Pulmonary Hypertension

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Edibe Karasu-Minareci ◽  
Irem Hicran Ozbudak ◽  
Gulay Ozbilim ◽  
Gulay Sadan
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arteries ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Sprague Dawley Rats ◽  
Pathway Activation ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

Phosphodiesterase type-5 (PDE-5) inhibitors are novel and important options for the treatment of pulmonary arterial hypertension (PAH). Therefore, we aimed to examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries isolated from rats with monocrotaline- (MCT-) induced pulmonary hypertension. MCT (60 mg/kg) or its vehicle was administered by a single intraperitoneal injection to 6-week-old male Sprague Dawley rats. Rats were sacrificed 21 days after MCT injection, and the main pulmonary arteries were isolated and then mounted in 20 mL organ baths. Concentration-response curves for vardenafil (10−10–10−5 M) were constructed in phenylephrine- (Phe-) precontracted rings. PAH caused marked rightward shift in the curves to vardenafil whereas maximal responses were not affected. Inhibition of NO synthase (L-NAME, 10−4 M) or guanylyl cyclase (ODQ, 10−5 M) caused similar attenuation in responses evoked by vardenafil. Moreover, contraction responses induced by CaCl2(3×10−5–3×10−2 M) were significantly reduced in concentration-dependent manner by vardenafil. In conclusion, vardenafil induced pulmonary vasodilatation via inhibition of extracellular calcium entry in addition to NO-cGMP pathway activation. These results provide evidence that impaired arterial relaxation in PAH can be prevented by vardenafil. Thus, vardenafil represents a valuable therapeutic approach in PAH besides other PDE-5 inhibitors.

scholarly journals The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6348
Author(s):  
Musaddique Hussain ◽  
Hazoor Bakhsh ◽  
Shahzada Khurram Syed ◽  
Malik Saad Ullah ◽  
Ali M. Alqahtani ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Vascular Diseases ◽  
Experimental Models ◽  
Dependent Manner ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Parallel Shift ◽  
Dual Blockade ◽  
Underlying Mechanisms

Parmotremaperlatumis traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatumin diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca+2 to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K+ (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K+ (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca+2 channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca+2 channels and muscarinic receptors, while the vasodilator effect might be owing to Ca+2 antagonism. Our results provide the pharmacological evidence that P. perlatumcould be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of P. perlatumas well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of P. perlatumin diarrhea, asthma, and hypertension treatment.

Inhibition of geranylgeranyltransferase inhibits bronchial smooth muscle hyperresponsiveness in mice

2009 ◽  
Vol 297 (5) ◽  
pp. L984-L991 ◽  
Author(s):  
Yoshihiko Chiba ◽  
Shunsuke Sato ◽  
Motohiko Hanazaki ◽  
Hiroyasu Sakai ◽  
Miwa Misawa
Keyword(s):  
Smooth Muscle ◽  
Rho Kinase ◽  
Selective Inhibition ◽  
Dependent Manner ◽  
Bronchial Smooth Muscle ◽  
Concentration Dependent Manner ◽  
Characteristic Features ◽  
Novel Strategy

Recent studies revealed an involvement of RhoA/Rho-kinase in the contraction of bronchial smooth muscle (BSM), and this pathway has now been proposed as a new target for asthma therapy. A posttranslational geranylgeranylation of RhoA is required for its activation. Thus selective inhibition of geranylgeranyltransferase may be a novel strategy for treatment of the BSM hyperresponsiveness in asthmatics. To test this hypothesis, we investigated the effect of a geranylgeranyltransferase inhibitor, GGTI-2133, on antigen-induced BSM hyperresponsiveness by using mice with experimental asthma. Mice were sensitized and repeatedly challenged with ovalbumin antigen. Animals also were treated with GGTI-2133 (5 mg/kg ip) once a day before and during the antigen inhalation period. Repeated antigen inhalation caused a BSM hyperresponsiveness to acetylcholine with the increased expressions of RhoA and the anti-farnesyl-positive 21-kDa proteins, probably geranylgeranylated RhoA. The in vivo GGTI-2133 treatments significantly inhibited BSM hyperresponsiveness induced by antigen exposure. In another series of experiments, BSM tissues isolated from the repeatedly antigen-challenged mice were cultured for 48 h in the absence or presence of GGTI-2133. Under these conditions, the putative geranylgeranylated RhoA was decreased in a GGTI-2133 concentration-dependent manner. The in vitro incubation with GGTI-2133 also inhibited BSM hyperresponsiveness induced by antigen exposure. These findings suggest that GGTI-2133 inhibits antigen-induced BSM hyperresponsiveness, probably by reducing downstream signal transduction of RhoA. Selective geranylgeranyltransferase inhibitors may be beneficial for the treatment of airway hyperresponsiveness, one of the characteristic features of allergic bronchial asthma.

Effect of bradykinin on airway neural responses in vitro

1992 ◽  
Vol 73 (4) ◽  
pp. 1537-1541 ◽  
Author(s):  
M. Miura ◽  
M. G. Belvisi ◽  
P. J. Barnes
Keyword(s):  
Matched Control ◽  
Electrical Field Stimulation ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Neural Responses ◽  
Response Curves ◽  
Electrical Field ◽  
Concentration Dependent Manner ◽  
Before And After

We investigated the effects of bradykinin (BK) on airway excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic nerves in vitro. Neural responses were elicited by electrical field stimulation in guinea pig airways in vitro before and after the addition of BK (10(-10)-10(-7) M). Captopril (10(-5) M) and phosphoramidon (10(-6) M) were added to prevent degradation of BK, and all neural responses were measured in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M). BK potentiated e-NANC responses in bronchi in a concentration-dependent manner (10(-10)-10(-7) M) without changing concentration-response curves to exogenously applied substance P (10(-10)-10(-5) M). BK significantly potentiated e-NANC neural constrictor responses by 22 +/- 7% at 10(-8) M (mean +/- SE, n = 5, P < 0.05) and 32 +/- 7% at 10(-7) M (n = 8, P < 0.01), compared with changes in time-matched control tissues (7 +/- 2%, n = 8). The potentiation of e-NANC responses by BK was abolished by pretreatment with a specific B2-receptor antagonist, HOE 140 (10(-7) M). Cholinergic constrictor responses elicited to electrical field stimulation were not affected by the addition of BK (up to 10(-7) M). These results suggest that BK potentiates e-NANC bronchoconstrictor responses prejunctionally via a B2-receptor.

scholarly journals Protective effect of aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in vitro

Folia Medica ◽  
2013 ◽  
Vol 55 (3-4) ◽  
pp. 76-79 ◽  
Author(s):  
Stefka V. Valcheva-Kuzmanova ◽  
Anna B. Beronova ◽  
Georgi Tz. Momekov
Keyword(s):  
Protective Effect ◽  
Fruit Juice ◽  
In Vitro Cytotoxicity ◽  
Dependent Manner ◽  
Cellular Viability ◽  
Platinum Drug ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Aronia Melanocarpa

ABSTRACT AIM: The aim of the present study was to investigate the protective potential of Aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in the human embryonal kidney cell line HEK293T. MATERIALS AND METHODS: The cellular viability was assessed using the MTT-dye reduction assay based on the reduction of the yellow tetrazolium dye MTT to a violet formazan product via the mitochondrial succinate dehydrogenase in viable cells. Cisplatin was applied in various concentrations either alone or after a 24-hour pretreatment of the cells with Aronia melanocarpa fruit juice at 0.1 and 0.05 mg/ml. The half maximal inhibitory concentrations (IC50 values) were derived from the concentration-response curves to cisplatin. RESULTS: Applied alone, the anticancer drug caused a prominent decrease of cellular viability with IC50 8.3 ± 1.1 μM. The juice proved to significantly ameliorate the in vitro cytotoxicity of the platinum drug, in a concentration-dependent manner. The pretreatment of the cells with Aronia melanocarpa fruit juice resulted in a significant increase (p < 0.001) of IC50 for cisplatin to 25.1 ± 2.7 μM (at 0.05 mg/ml) and 34.4 ± 3.4 μM (at 0.1 mg/ml), respectively. CONCLUSION: The protective effect of Aronia melanocarpa fruit juice observed in this study is most probably due to its well appreciated antioxidant activity as oxidative stress plays a central role in the toxic effects of cisplatin.

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