Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats.

BACKGROUND: This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis. METHODS: Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22. RESULTS: Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F. CONCLUSIONS: NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.

Magnetic graphene oxide functionalized alginate-g-poly(2-hydroxypropylmethacrylamide) nanoplatform for near-infrared light/pH/magnetic field-sensitive drug release and chemo/phototherapy.

Multifunctional nanoplatforms developed from natural polymers and graphene oxide (GO) with enhanced biological/physicochemical features have recently attracted attention in the biomedical field. Herein, a new multifunctional near-infrared (NIR) light-, pH- and magnetic field-sensitive hybrid nanoplatform (mGO@AL-g-PHPM@ICG/EP) is developed by combining iron oxide decorated graphene oxide nanosheets (mGO) and poly(2-hydroxypropylmethacrylamide) grafted alginate (AL-g-PHPM) copolymer loaded with indocyanine green (ICG) and etoposide (EP) for chemo/phototherapy. The functional groups, specific crystal structure, size, morphology, and thermal stability of the nanoplatform were fully characterized by XRD, UV, FTIR, AFM/TEM/FE-SEM, VSM, DSC/TG, and BET analyses. In this platform, the mGO and ICG, as phototherapeutic agents, demonstrate excellent thermal effects and singlet oxygen production under NIR-light (808 nm) irradiation. The XRD and DSC analysis confirmed the amorphous state of the ICG/EP in the nanoparticles. In vitro photothermal tests proved that the mGO@AL-g-PHPM@ICG/EP nanoparticles had outstanding light stability and photothermal conversion ability. The in vitro release profiles presented NIR light-, pH- and magnetic field-controlled EP/ICG release behaviors. In vitro experiments demonstrated the excellent antitumor activity of the mGO@AL-g-PHPM@ICG/EP against H1299 tumor cells under NIR laser. Benefiting from its low-cost, facile preparation, and good dual-modal therapy, the mGO@AL-g-PHPM@ICG/EP nanoplatform holds great promise in multi-stimuli-sensitive drug delivery and chemo/phototherapy.

Effects of edaravone on testicular torsion-detorsion injury in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the protective ability of edaravone on testicular torsion-detorsion injury in rats. METHODS: Eighteen adult male Sprague-Dawley rats were randomly divided into three groups: Sham group (control, n = 6); testicular torsion/detorsion (T/D group, n = 6) and T/D+edaravone (T/D+E group, n = 6). The spermatic cords of rats of the T/D group and the T/D+E group were rotated 720° in a clockwise direction and maintained for 120 min in this torsion position. Around 90 min after the torsion, edaravone at a dose of 10 mg/kg dissolved in saline was administered IP to the T/D+E group. The testicle was counter-rotated to its normal position to allow reperfusion for 4 h. Left testes of each animal were excised 240 min after beginning of reperfusion. Oxidative stress markers (TAS, TOS, SOD, and MDA) and apoptotic pathways (Caspase 3, Caspase 8, Caspase 9, Bcl-2, and Bax,) were assessed by ELISA methods. Also, testicles were subjected to the histopathologic and ultrasound examinations. RESULTS: Ultrasound imaging showed that edaravone reduced the surface area and increased vascularization in testicles with T/D (p < 0.0001, p < 0.05, respectively). Edaravone pretreatment markedly decreased the levels of MDA, TOS, Bcl-2, Bax, Caspase 3, Caspase 8, and Caspase 9 (p < 0.0001). Also, it increased significantly TAS levels (p < 0.0001) and reduced insignificantly SOD activity. Histopathologic examinations demonstrated that edaravone significantly attenuated the histological damage caused by T/D in testicles. CONCLUSION: Taken together, the findings indicate that pretreatment of edaravone has protective effect against testicular T/D injury.

Design and development of pH-responsive alginate-based nanogel carriers for etoposide delivery.

Recently, pH-responsive nanogels are playing progressively important roles in cancer treatment. The present study focuses on designing and developing pH-responsive alginate-based nanogels to achieve a controlled release of etoposide (Et) while enhancing its hydrophilicity. Alginate (ALG) is grafted with 2-hydroxypropyl methacrylamide (HPMA) through a microwave-supported method, and the chemical structure of the graft copolymer (ALG-g-PHPMA) was verified by 1H/13C NMR and FTIR techniques. The ALG-g-PHPMA and anticancer drug-loaded ALG-g-PHPMA@Et nanogels were obtained using an emulsion method, and their structures were characterized through FTIR, TG/DSC, AFM/TEM, BET, and DLS analyses. The ALG-g-PHPMA nanogels demonstrated a good drug encapsulation efficiency (79.60 %), displaying a pH-dependent release profile and an in vitro accelerated release of Et compared to the ALG nanogels. Thermal and BET analyses revealed enhanced stability, surface area, and porosity volume of the alginate nanogels. The grafting of PHPMA chains onto alginate altered the surface topology of the ALG nanogels, resulting in lower surface roughness. Furthermore, cytotoxicity tests showed the high biocompatibility of the ALG-g-PHPMA copolymer and its nanogels. The ALG-g-PHPMA@Et nanogels exhibited a higher anticancer effect on lung cancer (H1299) cells than free etoposide. These results suggest that the ALG-g-PHPMA nanogels can be applied as a pH-dependent nanoplatform for delivering anticancer drugs.

Development of chitosan-graphene oxide blend nanoparticles for controlled flurbiprofen delivery.

The use of natural polymeric nanoparticles (Nps) as drug carriers is a highly promising area of research in the field of drug delivery systems because of their high efficiency. In this study, flurbiprofen (FB) loaded chitosan-graphene oxide (CS-GO) blend Nps were synthesized as a controlled delivery system using the emulsion method. The crystalline, molecular, and morphological structures of the prepared CS-GO Nps were characterized using a variety of analytical methods, including Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-Ray diffractometry (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). It was found that the introduction of GO into the CS nanoparticle formulation increased its thermal stability. The range of the average particle size was between 362 ± 5.06 and 718 ± 2.21 nm, with negative zeta potential values between -7.67 ± 4.16 and - 27.93 ± 2.26 mV. The effects of the CS/GO ratio, the FB/polymer ratio, the amount of span 80, and the cross-linker concentration were assessed on FB release profiles. In vitro release studies displayed a two-stage release behaviour with a fast initial release of the FB, followed by sustained and extended release, and the incorporation of GO into the CS Nps made the FB release more sustained and controlled manner. Besides, the cytotoxicity test of the FB-loaded CS-GO Nps was studied through MTT assay, and it was found that they were biocompatible. Based on these findings, it can be inferred that the prepared CS-GO Nps might be a promising candidate drug carrier system for FB.

Preparation, characterization, and evaluation of antibacterial and cytotoxic activity of chitosan-polyethylene glycol nanoparticles loaded with amoxicillin as a novel drug delivery system.

In this study, nanoparticles of amoxicillin (AMX) were prepared using chitosan (CHI) and polyethylene glycol (PEG). The physicochemical properties of the particles were investigated by FT-IR, DSC, SEM, and zeta potential analyses. The nanoparticles showed a spherical shape, and the average size of formulations was within the range of 696.20 ± 24.86 - 359.53 ± 7.41 nm. Zeta potential data demonstrated that the formulations had positive surface charges with a zeta potential range of 21.38 ± 2.28 - 7.73 ± 1.66 mV. FTIR analysis showed that the drug was successfully entrapped in the nanoparticles. DSC results suggested that the drug was present in amorphous form in the polymer matrix. In vitro release studies demonstrated that the release pattern consisted of two phases, with an initial burst release followed by a controlled and sustained release. The MTT assay results on mouse fibroblast cell line indicated that the prepared formulations did not affect the viability of the cells. In the in vitro antibacterial activity test, it was found that the drug-loaded nanoparticles have AMX-equivalent antibacterial activity against E. coli, and S. aureus. These findings revealed that the obtained nanoparticles might be a promising and safe nanocarrier system for efficient delivery of AMX.

Amoxicillin has been encapsulated in PEG-CHI nanoparticles.The structure of nanoparticles was investigated by SEM, FTIR, and DSC studies.The nanoparticles showed an initial fast release followed by a slow release.PEG-CHI nanoparticles displayed equivalent antibacterial activity to amoxicillin, and a non-cytotoxic profile in healthy cells.

Effects of feed intake and water hardness on fluralaner pharmacokinetics in layer chickens.

BACKGROUND: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. OBJECTIVES: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. METHODS: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), area under the concentration-time curve values (AUC0-21d), half-life (t1/2), and other pharmacokinetic parameters were calculated. RESULTS: Although the highest maximum plasma concentration (Cmax) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the Cmax, tmax, t1/2, MRT0-inf_obs, Vz/Fobs, and Cl/F_obs parameters between the experimental groups. CONCLUSIONS: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.

The screening of the safety profile of polymeric based amoxicillin nanoparticles in various test systems.

Nanotechnology-based drugs show superiority over conventional medicines because of increased bioavailability, lower accumulation in non-target tissues, and improved therapeutic index with increased accumulation at target sites. However, it is important to be aware of possible problems related to the toxicity of these products, which have therapeutically superior properties. Accordingly, the present study was designed to investigate the safety profile of amoxicillin nanoparticles (AmxNPs) that we developed to increase the oral bioavailability of amoxicillin (Amx) in poultry. In the first part of the study, the genotoxicity potential of AmxNPs was evaluated using the Ames test and the in vitro comet assay. The results of Ames test showed that none of the tested concentrations of Amx and AmxNPs cause a significant increase in the revertant number of Salmonella typhimurium strains TA98, and TA100, either with or without metabolic activation. Similarly, the comet assay revealed that AmxNPs did not induce DNA damage at any of the concentrations used, whereas high-dose (200 µg/mL) of Amx caused a significant increase in the percentage of DNA in the tail. In the second part of the study, the toxicity potential of AmxNPs on broilers was investigated by measuring biochemical parameters. In vivo results demonstrated that AmxNps did not cause a significant change in biochemical parameters, whereas Amx increased ALT, glucose, and cholesterol levels at certain sampling times. The obtained findings suggest that AmxNPs could be a safe promising potential drug in drug delivery systems.

Development and characterization of polymeric-based nanoparticles for sustained release of amoxicillin - an antimicrobial drug.

In this study, amoxicillin (AMO)-loaded poly(vinyl alcohol)/sodium alginate (PVA/NaAlg) nanoparticles were prepared as a polymer-based controlled release system. The physicochemical properties of the obtained nanoparticles were investigated by XRD, DSC/TGA, particle size analyses and zeta potential measurements. The average particle sizes were in the range from 336.3 ± 25.66 to 558.3 ± 31.39 nm with negative zeta potential values from -41.86 ± 0.55 to -47.3 ± 2.76 mV. The influences of PVA/NaAlg ratio, span 80 concentration, exposure time to glutaraldehyde (GA) and the drug/polymer ratio on AMO release profiles were evaluated. In vitro drug release studies showed a controlled and pH dependent AMO release with an initial burst effect. XRD patterns and DSC thermograms of AMO-loaded nanoparticles revealed that the drug in the nanoparticles was in amorphous form, which was more stable than the crystalline form. The antibacterial activity of the optimal formulation was also investigated. The minimum inhibitory concentration (MIC) values of this formulation had the comparable antibacterial activity with that of pure AMO. These results indicate that the developed nanoparticles could be a promising candidate drug delivery system for AMO.

Effect of cocoa butter and sunflower oil supplementation on performance, immunoglobulin, and antioxidant vitamin status of rats.

This study investigated the effects of cocoa butter and sunflower oil alone and in combination on performance, some biochemical parameters, immunoglobulin, and antioxidant vitamin status in Wistar rats. Forty-eight male rats were assigned to four groups, consisting of 12 rats with 3 replicates. Control received balanced rat diet without oil, cocoa butter group received 3.5% cocoa butter, sunflower oil group received 3.5% sunflower oil, the last group received 1.75% sunflower oil + 1.75% cocoa butter supplementation in the rat diet for 8 weeks. The total feed consumption in sunflower oil group was statistically lower than in the other groups. The serum creatinine level was decreased in cocoa butter group compared to control. Triglyceride and VLDL cholesterol levels were decreased in only sunflower oil and only cocoa butter groups as compared to control. The level of Ig M was statistically lower in cocoa butter and cocoa butter + sunflower oil groups than in control and sunflower oil groups. There were no statistically important difference in vitamin concentrations among trial groups. It was concluded that the supplementation of cocoa butter in diet decreased Ig M level, while the supplementation of cocoa butter and sunflower oil alone decreased the triglyceride and VLDL cholesterol levels.