Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats.

Cisplatin (Cis) is a platinum-based antineoplastic drug used in various types of cancers. This drug can induce nephrotoxicity as a cause of acute kidney injury (AKI) by inducing oxidative stress and inflammation. Empagliflozin (Empa) is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. In addition to its blood glucose-lowering effect, Empa has been shown to exert anti-inflammatory and anti-oxidant properties. The current study aimed to investigate the protective effects of Empa on Cis-induced nephrotoxicity in rats. Male Wistar albino rats were divided into five groups, each of six rats: Sham group (received vehicle for 7 days), Control group (received vehicle for 7 days and Cis injection on day 2), Cis + Empa10 (received 10mg/kg Empa for 7 days and Cis injection on day 2), Cis + Empa30 (received 30mg/kg Empa for 7 days and Cis injection on day 2) and, Empa 30 (received 30mg/kg Empa for 7 days). One day after the last injection in each group, rats were weighed and then sacrificed to analyze the hematological, biochemical, and histological parameters. Cis markedly increased levels of inflammatory parameters such as renal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and myeloperoxidase (MPO) activity. Notably, malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine levels were enhanced after Cis administration. Also, the chemotherapeutic agent significantly reduced antioxidant indicators such as renal catalase (CAT), glutathione peroxidase (GpX), and superoxide dismutase (SOD). Furthermore, histopathological examinations also revealed severe renal damage following Cis treatment which was improved by Empa administration. Empa treatment at both doses (10 mg/kg and 30 mg/kg) reversed Cis-induced changes in all the above renal parameters. In conclusion, Empa has protective effects on Cis-induced nephrotoxicity by inhibition of oxidative stress and inflammation.

Preparation and investigation of indirubin-loaded SLN nanoparticles and their anti-cancer effects on human glioblastoma U87MG cells.

Indirubin, an ingredient in traditional Chinese medicine, is considered as an anti-cancer agent. However, due to its hydrophobic nature, clinical efficiency has been limited. Drug delivery via nanotechnology techniques open new windows toward treatment of cancerous patients. Glioblastoma multiforme (GBM) is the most severe and common type of brain primary tumors. Of common problems in targeting therapies of glioblastoma is the availability of drug in tumoric tissues. In this study, Indirubin loaded solid lipid nanoparticles were prepared and their therapeutic potentials and antitumoric effects were assessed on GBM cell line (U87MG). The SLNs were prepared with Cetyl palmitate and Polysorbat 80 via high-pressure homogenization (HPH) methods in hot mode. Then, properties of SLNs including size, zeta potential, drug encapsulation efficacy (EE %) and drug loading were characterized. SLNs morphology and size were observed using SEM and TEM. The crystalinity of formulation was determined by different scattering calorimetry (DSC). The amount of drug release and antitumor efficiency were evaluated at both normal brain pH of 7.2 and tumoric pH of 6.8. The prapared SLNs had mean size of 130 nm, zeta potential of -16 mV and EE of 99.73%. The results of DSC showed proper encapsulation of drug into SLNs. Drug release assessment in both pH displayed sustain release property. The result of MTT test exhibited a remarkable increment in antitumor activity of Indirubin loaded SLN in comparison with free form of drug and blank SLN on multiform GB. This study indicated that Indirubin loaded SLNs could act as a useful anticancer drugs.

Peptide functionalized poly ethylene glycol-poly caprolactone nanomicelles for specific cabazitaxel delivery to metastatic breast cancer cells.

Metastatic cancer is responsible for 90% of deaths in world. Usage of nano-carriers improve the delivery and efficacy of chemotherapeutic agents. Recent studies suggest that decoration of the surface of nano-carriers with various targeting agents may further improve their overall therapeutic efficacy. Using specified peptides in targeted drug delivery is a key point in recent researches. In this study, tumor metastasis targeting (TMT) homing peptide was applied as a targeting group to improve specific drug delivery to tumor cells. TMT peptide is conjugated to poly ethylene glycol-poly caprolactone (PEG-PCL) micellar nanoparticles as carriers for targeted delivery of cabazitaxel to metastatic breast cancer cells. Synthesis of PEG-PCL copolymer was performed by amidation reaction between carboxylic acid group of PEG and amine group of PCL. Nanomicelles were prepared via solvent evaporation method. TMT peptide was covalently conjugated onto nanomicelles through the amine group of PEG. TMT-PEG-PCL nanoparticles were analyzed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), dynamic light scattering (DLS), gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). Toxicity and cellular uptake of nanomicelles were investigated by in vitro cytotoxicity assays and confocal scanning microscopy in MCF-7 (non-metastatic breast cancer cells) and MDA-MB-231 (metastatic breast cancer cells). The final nanomicelles had about 110nm mean size and encapsulation efficiency of 82.5%. Treatment of metastatic breast cancer cells with targeted nanomicelles significantly increased the necrosis rate to 65%, compared to 33% in non-targeted nanomicelles and 8% in control group. The MDA-MB-231 cells treated with targeted nanomicelles exhibited a strong increase in the fluorescence intensity of coumarin in comparison to the cells treated with non-targeted nanomicelles (p<0.001). It could be concluded that the present carrier has the potential to be considered in treatment of metastatic breast cancer cells.

Antioxidant therapy in acute, chronic and post-endoscopic retrograde cholangiopancreatography pancreatitis: An updated systematic review and meta-analysis.

AIM: To investigate the efficacy and adverse effects of antioxidant therapy in acute pancreatitis (AP), chronic pancreatitis (CP) and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS: PubMed, Scopus, Google Scholar, Cochrane library database, and Evidence-based medicine/clinical trials published before August 2014 were searched. Clinical and laboratory outcomes of randomized trials of antioxidant therapy in patients with AP, CP and PEP were included. The methodological quality of the trials was assessed by the Jadad score based on the description of randomization, blinding, and dropouts (withdrawals). The results of the studies were pooled and meta-analyzed to provide estimates of the efficacy of antioxidant therapy. RESULTS: Thirty four trials out of 1069 potentially relevant studies with data for 4898 patients were eligible for inclusion. Antioxidant therapy significantly reduced the length of hospital stay in AP patients {mean difference -2.59 d (95%CI: -4.25-(-0.93)], P = 0.002}. Although, antioxidant therapy had no significant effect on serum C reactive protein (CRP) after 5-7 d in AP patients [mean difference -9.57 (95%CI: -40.61-21.48, P = 0.55], it significantly reduced serum CRP after 10 d {mean difference -45.16 [95%CI: -89.99-(-0.33)], P = 0.048}. In addition, antioxidant therapy had no significant effect on CP-induced pain [mean difference -2.13 (95%CI: -5.87-1.6), P = 0.26]. Antioxidant therapy had no significant effects on the incidence of all types of PEP [mean difference 1.05 (95%CI: 0.74-1.5), P = 0.78], severe PEP [mean difference 0.92 (95%CI: 0.43-1.97), P = 0.83], moderate PEP [mean difference 0.82 (95%CI: 0.54-1.23), P = 0.33], and mild PEP [mean difference 1.33 (95%CI: 0.99-1.78), P = 0.06]. Furthermore, while antioxidant therapy had no significant effect on serum amylase after less than 8 h sampling [mean difference -20.61 (95%CI: -143.61-102.39), P = 0.74], it significantly reduced serum amylase close to 24-h sampling {mean difference -16.13 [95%CI: -22.98-(-9.28)], P < 0.0001}. CONCLUSION: While there is some evidence to support antioxidant therapy in AP, its effect on CP and PEP is still controversial.

Biochemical and pathological evidences on the benefit of a new biodegradable nanoparticles of probiotic extract in murine colitis.

Efficacy of probiotics in the management of human inflammatory bowel disease (IBD) has been approved in the recent years. In the present work, the efficacy of a new biodegradable nanoparticles (NPs) of encapsulated and lyophilized probiotic extract (LPE) was examined in murine colitis. Colitis was induced by rectal instillation of trinitrobenzen sulfonic acid to male Wistar rats. The safety and effective dose of LPE was determined in a pilot study. To ease delivery into colon, LPE was encapsulated in chitosan-coated-poly (lactide co glycolide acid) NPs. After induction of colitis, animals in different groups received test compound in three doses by gavage for 10 days. Groups of sham, control (saline), and standard (dexamethasone) were also assigned. Colonic pathological examination, tumor necrosis factor alpha, interlukin (IL)-1ß, myeloperoxidase (MPO), and lipid peroxidation (LPO) were performed. LPE at all doses (273, 545, and 1100 mg/kg) had positive effects in reduction of pro-inflammatory cytokines, LPO, and MPO in a dose-dependent manner. The formulated compound containing medium dose of LPE was more efficient in mitigating the experimental colitis in comparison with that of high-dose LPE. It is concluded that LPE and its nanoparticle-encapsulated form are very much effective in control of colitis. Regarding safety of this compound, further studies can be conducted in patients with IBD.