Utility of Green Chemistry for Sustainable Fluorescence Derivatization Approach for Spectrofluorimetric Quantification of Pemetrexed as Antineoplastic Drug in Pharmaceutical Formulation and Spiked Human Plasma.

Pemetrexed is a chemotherapeutic medicine, under the trade name Alimta. Malignant pleural mesothelioma patients. Its application in lung cancer has been studied. Here in, a second spectrofluorimetric method was advanced for quantifying of Pemetrexed in pharmaceutical formulation and spiked human plasma. That method depends on fluorescence derivatization of Pemetrexed with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) at 75 °C in a (pH 9) of borate buffer to produce a fluorescent derivative which can be detected at 520 nm afterwards excitation at 460 nm. The method has been validated using ICH criteria, and it demonstrated linearity in a range of 2-120 ngmL-1. The proposed method was applied precisely and accurately for quantifying Pemetrexed within pharmaceutical formulation and spiking human plasma without any interferences. Moreover, the method's sustainability was evaluated and compared to the published method using two greenness assessment tools termed analytical eco-scale and Analytical GREENness (AGREE). That findings suggest that the method is more sustainable than the published method.

Utility of green chemistry for feasible spectrofluorometric determination of trifluridine via metal complexation: Application to dosage forms.

The goal of the current research was to establish a quick and practical fluorometric technique for trifluridine analysis. The approach relied on the drug's complex formation with the zinc ion to produce a high-fluorescence product. The fluorescence was further enhanced by adding sodium dodecyl sulfate, and it was observed at 450 nm following excitation at 400 nm. With a determination coefficient of 0.9994, the association between emission intensity and trifluridine concentration was linear between 1 and 125 ng mL-1. The quantitation limit was 0.987 ng mL-1 while 0.333 ng mL-1 was the detection limit. The buffer type, pH and concentration, type of surfactant and concentration, and finally the diluting solvent were among the reaction conditions that were closely examined. With great precision and reliability, the drug in question was quantified using this method in dosage formulations. The proposed method's level of greenness was assessed using two methodologies: the analytical greenness metric (AGREE) and the Green Analytical Procedure Index (GAPI).

Utility of green chemistry for sustainable fluorescence derivatization approach for spectrofluorimetric quantification of Darolutamide as antineoplastic drug in pharmaceutical formulation and spiked human plasma.

Darolutamide is an oral nonsteroidal androgen receptor antagonist used to delay the process of prostate cancer to metastatic disease and to increase the quality of life for people with advanced prostate cancer. Here, a second spectrofluorimetric method was advanced for quantifying Darolutamide in pharmaceutical formulation and spiked human plasma. This method depends on the fluorescence derivatization of Darolutamide with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) at 75°C in a (pH 9) of borate buffer to produce a fluorescent derivative that can be detected at 520 nm after excitation at 460 nm. The method has been validated using ICH criteria, and it demonstrated linearity in the range 5-200 ng ml-1 . The limit of detection (LOD) and limit of quantitation (LOQ) were 1.15 and 3.84 nm, respectively. The proposed method was applied precisely and accurately for quantifying Darolutamide within the pharmaceutical formulation and spiking human plasma without any interferences. Moreover, the method's sustainability was evaluated and compared with the published method using two greenness assessment tools termed analytical eco-scale and Analytical GREEnness (AGREE). These findings suggest that the method is more sustainable than the published method.

Green sensitive spectrofluorimetric determination of pemetrexed as antineoplastic drug: Application in pharmaceutical dosage forms and spiked human plasma.

A recent antineoplastic medication is pemetrexed, this medicine is now being developed and produced on a large scale, thus approaches for quality control are urgently needed. Spectrofluorimetric guidelines for the simple estimation of pemetrexed were validated. Pemetrexed's assay depends on observations of its native fluorescence at wavelengths 275/450 nm and pH 4. The proposed approach was also used to identify the examined drug in both its formulation and in human plasma that had been spiked.

Green micellar spectrofluorimetric determination of α-mangostin found in herbal products as antioxidant and other biological activities beneficial to human health.

Pharmaceutical product quality control (QC) needs quick, sensitive and economical procedures to deliver high throughput at low cost, which is the key factor considered by such economic facilities. To lessen the risky effects of research laboratories, researchers must take into account the ecological impacts. α-Mangostin (MAG) exhibit anti-inflammatory, antioxidant, anticancer, anti-allergic, antibacterial, antifungal, antiviral and antimalarial activities. Based on the spectrofluorimetric approach, a novel straightforward, sensitive and environmentally friendly method for MAG determination was developed and validated. Many variables were investigated to improve MAG native fluorescence, including solvent type, buffers, pH and additional surfactants. The best MAG fluorescence sensitivity was found in Britton-Robinson buffer (pH 4) at 450 nm after irradiation at 350 nm in the concentration range of 5-50 ng ml-1 . The technique was successfully used to determine the presence of MAG in both its approved dose forms and in samples of spiked human plasma, as per FDA standards for validation. According to their evaluation on two recent greenness criteria (GAPI [Green Analytical Procedure Index] and AGREE [Analytical GREEnness]), the suggested approach has been shown to be environmentally beneficial because it normally uses biodegradable chemicals in solvent-free aqueous phases.

Utilization of erythrosine B in spectrofluorimetric quenching analysis of amlodipine and perindopril in pharmaceutical and biological matrices.

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25-3.0 µg ml-1 , with a correlation coefficient of 0.9996 for AML, and 0.1-1.5 µg ml-1 , with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.

Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs: tepotinib, sotorasib, and darolutamide in their dose forms and biological liquids utilizing mercurochrome.

An approved, straightforward, fast, and delicate spectrofluorimetric strategy was developed for the estimation of tepotinib (TEPO), sotorasib (SOTO), and darolutamide (DARO) as new antineoplastic drugs. The spectrofluorimetric strategy was based on quantitative fluorescence quenching of MER at 538 nm after being excited at 350 nm by the addition of the cited drugs in the presence of acetate buffer (pH 3.5). The degree of fluorescence quenching was directly proportional to the concentrations of the cited drugs within the concentration range of 0.5-10.0, 0.2-10, and 0.4-10.0 µg ml-1 for TEPO, SOTO, and DARO, respectively. Mean ± standard deviation (SD) were calculated for the studied drugs as follows; 99.9 ± 0.87, 99.72 ± 1.08, and 100.21 ± 1.44, for TEPO, SOTO, and DARO, respectively. Limit of detection (LOD) values were 0.16, 0.05, and 0.11 µg ml-1 , whereas limit of quantitation (LOQ) values were 0.5, 0.15, and 0.36 µg ml-1 for TEPO, SOTO, and DARO, respectively. Statistical comparison through detailed strategies produced greater understanding and found that there were no noteworthy contrasts in exactness and exactness between strategies. The proposed strategy was used effectively to analyze the measurement of different forms of the examined drugs. Moreover, the recommended fluorimetric strategy was used for examination of TEPO, SOTO, and DARO in human plasma and urine tests.

A systematic review of the applications of Expert Systems (ES) and machine learning (ML) in clinical urology.

BACKGROUND: Testing a hypothesis for 'factors-outcome effect' is a common quest, but standard statistical regression analysis tools are rendered ineffective by data contaminated with too many noisy variables. Expert Systems (ES) can provide an alternative methodology in analysing data to identify variables with the highest correlation to the outcome. By applying their effective machine learning (ML) abilities, significant research time and costs can be saved. The study aims to systematically review the applications of ES in urological research and their methodological models for effective multi-variate analysis. Their domains, development and validity will be identified. METHODS: The PRISMA methodology was applied to formulate an effective method for data gathering and analysis. This study search included seven most relevant information sources: WEB OF SCIENCE, EMBASE, BIOSIS CITATION INDEX, SCOPUS, PUBMED, Google Scholar and MEDLINE. Eligible articles were included if they applied one of the known ML models for a clear urological research question involving multivariate analysis. Only articles with pertinent research methods in ES models were included. The analysed data included the system model, applications, input/output variables, target user, validation, and outcomes. Both ML models and the variable analysis were comparatively reported for each system. RESULTS: The search identified n = 1087 articles from all databases and n = 712 were eligible for examination against inclusion criteria. A total of 168 systems were finally included and systematically analysed demonstrating a recent increase in uptake of ES in academic urology in particular artificial neural networks with 31 systems. Most of the systems were applied in urological oncology (prostate cancer = 15, bladder cancer = 13) where diagnostic, prognostic and survival predictor markers were investigated. Due to the heterogeneity of models and their statistical tests, a meta-analysis was not feasible. CONCLUSION: ES utility offers an effective ML potential and their applications in research have demonstrated a valid model for multi-variate analysis. The complexity of their development can challenge their uptake in urological clinics whilst the limitation of the statistical tools in this domain has created a gap for further research studies. Integration of computer scientists in academic units has promoted the use of ES in clinical urological research.

Utilization of a complex arrangement approach for spectroscopic examination with Eosin Y of various cephalosporins in their pure or pharmaceutical dosage forms, and in human plasma.

Approved, basic, effective and successful spectroscopic strategies (spectrophotometric and spectrofluorimetric) were created to measure seven cephalosporins: cefpiramide (I), cefuroxime (II), cefoxitin (III), ceftazidime (IV), cefpirome (V), ceftobiprole (VI), and ceftriaxone (VII). These strategies used a two-fold complex arrangement response for the drug amino groups with Eosin Y (EY). The examined drugs were determined spectrophotometrically at 542-550 nm in acetic acid derivative buffer. The examined drugs were determined spectrofluorimetrically by measuring their quenching effect on EY local fluorescence at 545 nm after excitation at 305 nm. The absorbance-intensity plots were rectilinear over the ranges 20-100, 10-130, 20-220, 30-230, 10-210, 20-180 and 10-130 µg ml-1 for I, II, III, IV, V, VI, and VII samples, respectively. The fluorescence-intensity plots were rectilinear over the ranges 0.5-1.5, 0.1-0.9, 0.3-1.5, 0.5-2.5, 0.1-0.9, 0.5-2.5 and 0.1-1.0 µg ml-1 for I, II, III, IV, V, VI, and VII samples, respectively. The recommended materials were certified as adhering to International Council for Harmonisation (ICH) guidelines and were used to examine the tested drugs in different dosage forms and in human plasma tests. The approved materials matched the reference materials.

Highly sensitive spectrofluorimetric procedure for the assay of phenothiazine derivatives in the presence of their sulfoxide oxidized product.

A validated straightforward and sensitive spectrofluorimetric procedure was developed to assay trifluoperazine hydrochloride, promethazine hydrochloride, and perazine maleate. The procedure was dependent on oxidation of the investigated phenothiazines using a known excess of ammonium cerium sulfate as oxidizing agent and overseeing the fluorescence intensity of the resultant Ce3+ ion as the product of this reaction at λcx = 254 nm. and λem = 355 nm. Various parameters controlling the reaction were investigated and optimized. Linear calibration graphs were found in the general concentration range 5-30 ng/ml with a general correlation coefficient range 0.9994-0.9995. Limits of detection were 0.97, 0.70 and 0.56 ng/ml, whereas limits of quantification were 3.24, 2.12 and 1.89 ng/ml for trifluoperazine hydrochloride, promethazine hydrochloride and perazine maleate, respectively. The procedure was implemented successfully for analyses of the cited drugs in their trade dosage preparations such as tablets and syrups. The effect of possible interference from common excipients and their sulfoxide oxidized product was studied and the procedure showed good recovery of the drugs under study in their available dosage preparations. The possible effect of structure variation of the studied drugs on the experimental conditions and sensitivity observed with each one was also discussed.

A multicentre integration of a computer-led follow-up of prostate cancer is valid and safe.

OBJECTIVE: To test a computer-led follow-up service for prostate cancer in two UK hospitals; the testing aimed to validate the computer expert system in making clinical decisions according to the individual patient's clinical need with a valid model accurately identify patients with disease recurrence or treatment failure based on their blood test and clinical picture. PATIENTS AND METHODS: A clinical-decision support system (CDSS) was developed from European (European Association of Urology) and national (National Institute for Health and Care Excellence) guidelines along with knowledge acquired from Urologists. This model was then applied in two UK hospitals to review patients after prostate cancer treatment. These patients' data (n = 200) were then reviewed by two independent urology consultants (blinded from the CDSS and the other consultant's rating) and the agreement was calculated by kappa statistics for validation. The second endpoint was to verify the system by estimating the system reliability. RESULTS: The two individual urology consultants identified 12% and 15% of the patients to have potential disease progression and recommended their referral to urology care. The kappa coefficient for the agreement between the CDSS and the two consultants was 0.81 (P < 0.001) and 0.84 (P < 0.001). The agreement amongst both specialist was also high with k = 0.83 (P < 0.001). The system reliability was estimated on all cases and this demonstrated 100% repeatability of the decisions. CONCLUSION: A CDSS follow-up is a valid model for providing safe follow-up for prostate cancer.

Transition Metal Dichalcogenide Atomic Layers for Lithium Polysulfides Electrocatalysis.

Lithium-sulfur (Li-S) chemistry is projected to be one of the most promising for next-generation battery technology, and controlling the inherent "polysulfide shuttle" process has become a key research topic in the field. Regulating intermediary polysulfide dissolution by understanding the metamorphosis is essential for realizing stable and high-energy-density Li-S batteries. As of yet, a clear consensus on the basic surface/interfacial properties of the sulfur electrode has not been achieved, although the catalytic phenomenon has been shown to result in enhanced cell stability. Herein, we present evidence that the polysulfide shuttle in a Li-S battery can be stabilized by using electrocatalytic transition metal dichalcogenides (TMDs). Physicochemical transformations at the electrode/electrolyte interface of atomically thin monolayer/few-layer TMDs were elucidated using a combination of spectroscopic and microscopic analysis techniques. Preferential adsorption of higher order liquid polysulfides and subsequent conversion to lower order solid species in the form of dendrite-like structures on the edge sites of TMDs have been demonstrated. Further, detailed electrochemical properties such as activation energy, exchange current density, rate capabilities, cycle life, etc. have been investigated by synthesizing catalytically active nanostructured TMDs in bulk quantity using a liquid-based shear-exfoliation method. Unveiling a specific capacity of 590 mAh g-1 at 0.5 C rate and stability over 350 cycles clearly indicates yet another promising application of two-dimensional TMDs.

Electrocatalytic Polysulfide Traps for Controlling Redox Shuttle Process of Li-S Batteries.

Stabilizing the polysulfide shuttle while ensuring high sulfur loading holds the key to realizing high theoretical energy of lithium-sulfur (Li-S) batteries. Herein, we present an electrocatalysis approach to demonstrate preferential adsorption of a soluble polysulfide species, formed during discharge process, toward the catalyst anchored sites of graphene and their efficient transformation to long-chain polysulfides in the subsequent redox process. Uniform dispersion of catalyst nanoparticles on graphene layers has shown a 40% enhancement in the specific capacity over pristine graphene and stability over 100 cycles with a Coulombic efficiency of 99.3% at a current rate of 0.2 C. Interaction between electrocatalyst and polysulfides has been evaluated by conducting X-ray photoelectron spectroscopy and electron microscopy studies at various electrochemical conditions.

Effect of mini-dose epidural dexmedetomidine in elective cesarean section using combined spinal-epidural anesthesia: a randomized double-blinded controlled study.

BACKGROUND: Combined spinal-epidural anesthesia is commonly used for elective cesarean section. Our study aimed to evaluate the effect of adding dexmedetomidine to epidural bupivacaine and fentanyl in patients undergoing elective cesarean section using combined spinal-epidural anesthesia. METHODS: Eighty healthy women at term were randomly assigned to two groups: a control group (n = 40; "Bup/Fen group") received combined spinal-epidural anesthesia with intrathecal hyperbaric bupivacaine 5 mg and an epidural mixture of 10 mL plain bupivacaine 0.25 % and fentanyl 50 µg, whereas the study group (n = 40; "Dex/Bup/Fen group") received 1 mL epidural dexmedetomidine 0.5 µg/kg in addition. The primary outcome measure was the difference between the groups in the supplementary fentanyl analgesic required. The quality of surgical anesthesia, incidences of hypotension and bradycardia, APGAR scores, intraoperative pain assessment, and onset of postoperative pain, sedation score, and side effects were recorded. RESULTS: There was no statistically significant difference between the groups regarding block characteristics. Significantly less intraoperative and postoperative fentanyl were required by the Dex/Bup/Fen group (P = 0.015 and P = 0.0011, respectively). There was no statistically significant difference between the groups regarding sedation score or the incidences of hypotension, nausea and vomiting, dizziness, and pruritus. CONCLUSIONS: The addition of mini-dose epidural dexmedetomidine 0.5 µg/kg as a single injection to bupivacaine fentanyl in women undergoing elective cesarean section with combined spinal-epidural anesthesia improved intraoperative conditions and the quality of postoperative analgesia.

Spectrofluorimetric determination of tapinarof via Zn (II) complexation and assessment of its topical dosage application.

Topical tapinarof is used to treat plaque psoriasis (a skin disease in which red and scaly patches form are appeared on some areas of the body). The goal of the current research is to establish a facile and rapid fluorimetric technique for tapinarof analysis. The approach relied on the reaction between the drug and zinc ion through metal complexation to produce a highly-fluorescent product. The fluorescence was further enhanced by adding sodium dodecyl sulfate, and it was observed at 542 nm following excitation at 497 nm. With a correlation coefficient of 0.9997, the association between emission intensity and tapinarof concentration was linear between 2.0 and 120 ng mL-1. 1.021 ng mL-1 was the quantitation limit while 0.366 ng mL-1 was the detection limit. The buffer type, pH and concentration, type of surfactant and concentration, and finally the diluting solvent were among the reaction conditions that were closely examined and it was found that the optimum conditions were obtained upon employing teorell-stenhagen buffer optimized at pH 6.0, 1.38 × 10-2 M SDS and distilled water as a solvent are the suitable choice. With great precision and reliability, the drug under study was quantified using this method in ointment formulations. The proposed method's level of greenness was assessed using two methodologies: the analytical greenness metric (AGREE) and the Green Analytical Procedure Index (GAPI), with good recovery results ensuring high efficiency of the proposed approach on analysis of ointment without any interference from additives and excipients.

Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma.

A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green fluorescence. Relative fluorescence intensity of the products was measured at λ exc 398 nm and λ em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N-dealkylation or oxidation of the corresponding sulphoxides or sulphones.

Simultaneous Determination of Ceftazidime in Three Different Pharmaceutical Preparations Combined with Either Tazobactam, Tobramycin or Sulbactam by HPTLC-Spectrodensitometric Method.

A new, simple hight performance thin layer chromatography (HPTLC)-Spectrodensitometric strategy was created and approved for the synchronous estimation of four antibacterial specialists: ceftazidime (CEF), tazobactam (TAZ), tobramycin (TOB) and sulbactam (SUL). The four compounds were separated on TLC aluminum plates covered with silica gel 60 F254, using chloroform-acetonitrile-methanol-ammonia (4:1:0.5:0.15, v/v/v/v) as a mobile phase at 254 nm. Linear correlation was obeyed over the concentration ranges of 12.0-72.0, 2.0-12.0, 3.0-18.0 and 10.0-50.0 µg mL-1 for CEF, TAZ, TOB and SUL, respectively. The proposed approach is efficient, repeatable and convenient as a flexible method for the quality control of diverse combinations of these pharmaceuticals in various pharmaceutical preparations, with high percent recoveries that are highly consistent with labeled data. When the findings of the proposed technique were compared to those of the comparison methods, there were no critical contrasts in terms of precision and accuracy.

Proniosomal Gel-Loaded Phosphodiesterase Inhibitors (Sildenafil, Vardenafil, and Tadalafil): Prospects for Topical Penile Therapy of Tadalafil for Treatment of Erectile Dysfunction.

Oral phosphodiesterase inhibitors have emerged as a game changer for the treatment of erectile dysfunction (ED) since attaining FDA approval for its first member, sildenafil, in 1998. Topical penile therapy could be a viable replacement for oral medication that would transform the treatment of ED for many decades to come. This innovative idea could offer a safer topical alternative with less vision and cardiovascular side effects than the oral route. This work aims at developing proniosomal gels for three selected members (sildenafil, vardenafil, and tadalafil) and investigating the proniosomal gels on a rodent model. Niosomes derived from the parent proniosomal gels were characterized for entrapment efficiency (EE%), size, polydispersity index (PDI), zeta potential, and morphology. Proniosomal gels were evaluated for skin permeation, in vivo mating behaviors, and biochemical assays of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) post penile topical administrations. The optimized proniosomes loaded with tadalafil (F1-T) were compared with oral tablets (Cialis®). Proniosomal gels demonstrated significant enhancement of skin penetration by up to 5.5-fold, compared to control topical suspension. Tadalafil-loaded proniosomes showed superior skin permeability over sildenafil- and vardenafil-loaded proniosomes. In addition, significant improvement was noticed regarding intromission number, intromission ratio, NO, and cGMP for the proniosomal gel F1-T, compared to the untreated control. No statistically significant (p > 0.05) differences in sexual performance or biochemical parameters (NO and cGMP levels) were recorded among orally and topically (tadalafil proniosomal gel) administered groups. These findings support tadalafil topical penile therapy as a promising alternative to the oral route.

Synchronous fluorescence as a green and selective method for the simultaneous determination of finasteride and tadalafil in dosage form and spiked human plasma.

Finasteride and tadalafil are combined in a pharmaceutical capsules called Entadfi™, that has received FAD approval. It was indicated for the management of male benign prostatic hyperplasia-related urinary tract issues. In the current study, finasteride and tadalafil concentrations in raw form, laboratory prepared mixtures, pharmaceutical preparation and spiked human plasma were all quantitatively estimated using a sensitive synchronized fluorescence spectroscopic approach united with first derivative. When excited at 260 nm, finasteride display its emission at 320 nm. Yet, when excited at 280 nm, tadalafil displayed its emission at 340 nm. The application of micellar surfactant as sodium dodecyl sulphate (SDS) significantly increased the fluorescence intensity.The overlapping of the fluorescence spectra was entirely eliminated by derivatizing the synchronous spectra to the first derivative, which also made it possible to simultaneously quantify the cited drugs. Without interfering with one another, the first-order synchronous spectra of tadalafil and finasteride at 320 and 330 nm, respectively. The approach revealed linearity alongside an acceptable correlation coefficient for finasteride and tadalafil concentrations over the range of 10 -50 ng/mL. That approach was utilized to estimation of the cited drugs in dosage forms, simultaneously with %recoveries for tadalafil and finasteride of 99.62 ± 0.78 and 100.19 ± 0.60, respectively. Also, four various tools, the national environmental method index, the AGREE evaluation method, the green analytical procedure index and the analytical eco-scale were used to evaluate how environmentally friendly the given approach was. With regard to the metrics of the greenness aspects, the proposed approach appeared to be better than the previously published spectrophotometric methods and HPLC.

Cardioprotective effects of ozone oxidative preconditioning in an in vivo model of ischemia/reperfusion injury in rats.

BACKGROUND: Several studies have demonstrated the beneficial effects of ozone oxidative preconditioning in several pathologies characterized by cellular oxidative and inflammatory burden. The present study was designed to investigate the cardioprotective effects of oxidative preconditioning in ischemia/reperfusion (I/R) injury. METHODS: Rats were randomly assigned into five groups. Groups 1 and 2 were normal and I/R groups, respectively. Two of the other groups received two different doses of ozone therapies by rectal insufflations. The last group received vehicle (oxygen). Rats were subjected to myocardial I/R (40 min/10 min). Heart rate and ventricular arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NO(x)) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. Histological examination was also performed to visualize the protective cellular effects. RESULTS: Both doses of ozone therapy were equally protective in reducing CK-MB release. However, the higher dose was more effective in reducing oxidative stress, lactate accumulation, elevated MPO activity and plasma NO(x) as well as preserving myocardial adenine nucleotides. Histological examination also revealed better improvement with a higher dose of ozone therapy compared to the I/R group. CONCLUSION: Ozone therapy can afford significant cardioprotection against biochemical and histological changes associated with I/R injury.