Protective effects of arbutin against doxorubicin-induced cardiac damage.

BACKGROUND: Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity. METHODS AND RESULTS: The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20 mg/kg) to induce cardiac toxicity, a group treated with arbutin (100 mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1ß and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1ß levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue. CONCLUSION: The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.

Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract.

Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to determine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their effect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The effects of different doses (0.0390625-20 µg/mL) of NPs on cell viability were determined by MTT assay. The effect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fixed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that inflammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-ß associated with wound healing. The findings reveal the antimicrobial effect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.

Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis.

This study was designed to investigate the protective effects of Centella asiatica (CA) on cisplatin-induced hepatotoxicity and to clarify the underlying mechanism by biochemical, molecular, immunohistochemical, and histopathological analyses. Rats were pre-treated with two doses of CA (100 and 200 mg/kg, p.o.) for 14 consecutive days. Then, on the 15th day, hepatotoxicity was induced by a single cisplatin injection (10 mg/kg i.p.). On the 18th day, the rats were euthanized. CA effectively alleviated cisplatin-induced hepatic injury via reduction in AST, ALT, and ALP enzymes and a decrease in oxidative stress (decreased MDA and ROS, and increased SOD, CAT, and GSH). CA also mitigated the inflammatory damage by the inhibition of TNF-α, IL-1ß, and NF-κB. The liver expression of caspase-3 and Bax was downregulated, while Bcl-2 was upregulated. Moreover, immunohistochemical results confirmed the recovery with CA by downregulation of iNOS and 8-OHdG expression. These results showed that with its antioxidant, anti-inflammatory, and anti-apoptotic activities, CA could help alleviate the hepatotoxic effects of cisplatin chemotherapy.

Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence.

The objective of this study was to elucidate the effects of syringic acid on thioacetamide-induced hepatic encephalopathy which is a complex serious syndrome with neuropsychiatric abnormalities related to acute liver dysfunctions like cirrhosis. Rats were treated with syringic acid (50 and 100 mg/kg, p.o.) for 14 days in treatment groups. Hepatic encephalopathy was induced by three doses of (200 mg/kg i.p.) thioacetamide injection. Syringic acid effectively alleviated thioacetamide-induced hepatic injury via reduction in ammonia, AST, ALT, ALP, LDH and decrease in oxidative stress (decreased MDA, ROS and increased SOD and GSH). Syringic acid also attenuated inflammatory injury by suppressing TNF-α, IL-1ß, and NF-κB and increasing IL-10. The caspase-3 expression was also down-regulated in both liver and brain tissues. Immunohistochemical results confirmed the recovery with syringic acid by downregulation of iNOS, 8-OHdG and GFAP expression. Syringic acid decreased the deteriorating effects of thioacetamide as seen by reduced ammonia concentration and also preserved astrocyte and hepatocyte structure. The behavioral test results from elevated plus maze test, similar to the open-field locomotor test results, confirmed that syringic acid can reverse behavioral impairments. In conclusion, syringic acid exerted hepatoprotective and neuroprotective effects against hepatic encephalopathy by mitigating hepatotoxicity biomarkers, exerting antioxidant, anti-inflammatory effects in addition to suppressing hyperammonemia.

Orally disintegrating tablet containing carbamazepine and levetiracetam: formulation and in vitro and in vivo characterization.

This study aimed to prepare and characterize the orally disintegrating tablet (ODT) formulations containing the combination of levetiracetam (LEV) and carbamazepine (CBZ) (CBZ + LEV combination) for the treatment of epilepsy. The ODT formulations were prepared using the lyophilization (L) and direct compression (DC) methods. The flowability of the mixed powders used for DC formulation was evaluated. The quality control tests for the ODTs were performed. Also, the antiepileptic effects of pure drugs, their combination, and the suspension of CBZ + LEV-DC-ODT formulation were evaluated in the rats with pentylenetetrazole (PTZ)-induced epilepsy model. The obtained results for the mixed powders of the DC formulation (angle of repose: 26.18 ± 0.794°; compressibility index: 15.24 ± 0.764%) suggest that the flow properties of the powder blend were suitable for the preparation of CBZ + LEV-ODT using DC method. The mean values of diameter and hardness of L-ODTs and DC-ODTs were found to be 16.87 mm and 16.18 mm and 11.96 N and 30.11 N, respectively. The friability of both formulations was <1%. Both formulations were disintegrated in seconds. Drugs in L-ODT had faster dissolution than those in DC-ODT. Compared to the seizure scores obtained for the groups treated with LEV or CBZ, generally, there was a higher decrease in seizure scores in the groups treated with CBZ + LEV combination or the suspension of CBZ + LEV-DC-ODTs. Consequently, the ODT formulations containing the CBZ + LEV combination might be beneficial in the treatment of epilepsy.

Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study.

Aim: Cisplatin is a widely used and highly effective anti-cancer agent and one of the limiting side effects of cisplatin is ocular toxicity. Achillea millefolium, also known as yarrow, is a plant that has been used for many years to treat various health problems including chemotherapy-related toxicities. Methods: The present investigation was designed to evaluate the biochemical, molecular and histopathological effects of Achillea Millefolium on cisplatin-induced oxidative and inflammatory ocular damage in rats. Twenty-four adult male rats were assigned randomly to four groups (n = 6) as (1) control, (2) cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Achillea millefolium (200 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Levels of total antioxidant capacity and total oxidant status, SOD, MDA, IL-1ß, and IL-10 were measured in ocular tissue. The mRNA expressions of TNF-α, nuclear factor kappa B and Caspase-3 were evaluated. Also, ocular sections were evaluated histopathologically.Results: Achillea Millefolium upregulated ocular antioxidant enzymes and downregulated inflammation. The SOD activity and total antioxidant capacity increased whereas total oxidant status and MDA levels decreased significantly at high dose group. High dose Achillea millefolium treatment reduced the IL-1ß concentrations, whereas IL-10 levels increased significantly in that group. Moreover, we observed that Achillea millefolium restored ocular histopathological structure and significantly suppressed apoptosis by reducing the expression of Caspase-3.Conclusion: Collectively, our results suggest that Achillea millefolium have protective effects against cisplatin-induced ocular toxicity and is a promising adjuvant therapy with the potential to prevent cisplatin related ocular toxicity.

Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses.

The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8 mg/kg, intraperitoneally), (3) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (200 mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1ß levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2'-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility.

Preparation of CoS nanoparticles-cisplatin bio-conjugates and investigation of their effects on SH-SY5Y neuroblastoma cell line.

Neuroblastoma is one of the most widely seen under the age of 15 tumors that occur in the adrenal medulla and sympathetic ganglia. Cisplatin, an antineoplastic drug, is a Platinum-based compound and is known to inhibit the proliferation of neuroblastoma cells. Effective applications of nanoparticles in biomedical areas such as biomolecular, antimicrobial detection and diagnosis, tissue engineering, theranostics, biomarking, drug delivery, and anti-cancer have been investigated in many studies. This study aims to prepare the bioconjugates of CoS (cobalt sulfide) nanoparticles (NPs) with cisplatin combination groups and to evaluate their effects on the neuroblastoma cell line. Nanoparticle synthesis was done using the green synthesis technique using Punica granatum plant extract. The size and shape of CoS NPs were characterized by SEM, FT-IR, and XRD. Zeta potential was confirmed by the DLS study. For this purpose, the SH-SY5Y neuroblastoma cell line was cultured in a suitable cell culture medium. Cisplatin 5 µg and different concentrations (Cisplatin + CoS NPs bioconjugates (5, 10, 25, 50, 75 µg) doses were applied to SH-SY5Y neuroblastoma cell lines for 24 h. TAC, TOS and MTT tests were performed 24 h after the application. According to the MTT test results, cisplatin and CoS NP combinations reduced the proliferation of neuroblastoma cells by 78 to 57% compared to the cisplatin control. From the findings obtained; the most effective Bio-conjugate group was Cisplatin 5 µg/mL + CoS 75 µg/mL.

Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies.

Objective: The aim of this study was to develop the PLGA nanoparticles (NPs) containing carbamazepine (CBZ) and levetiracetam (LEV) combination (CBZ + LEV) for the treatment of epilepsy and to in vitro characterize the prepared NPs.Significance: LEV and CBZ, which are antiepileptic drugs, are used in the treatment of epilepsy. Nano-sized formulations are prepared to use for different purposes such as to improve the solubility/the physicochemical properties and bioavailability of drugs, to decrease their doses and frequency of administration, and to reduce side effects of drugs.Methods: CBZ + LEV-PLGA-NPs were prepared by a modified nanoprecipitation method and in vitro and in vivo characterized. Also, the antiepileptic effect of the NPs was evaluated in vivo in a rat epilepsy model.Results: The mean particle size and zeta potential of CBZ + LEV-PLGA-NPs were 180.62 ± 6.260 nm and -27.08 ± 3.110 mV, respectively. The values of encapsulation efficiency (EE%) of CBZ and LEV were 51.00 ± 5.944% and 2.05 ± 0.367%, respectively. CBZ showed a biphasic release profile with initial burst release followed by a sustained release. Ninety percent of CBZ was released from NPs within two days; however, % LEV release from NPs reached about 80% within 30 min.Conclusion: Our results showed that a decrease in seizure scores in the group treated with CBZ + LEV was observed and also, CBZ + LEV and CBZ + LEV-PLGA-NPs had similar antiepileptic activity. The NPs containing CBZ + LEV might be beneficial in the treatment of epilepsy.