The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.

The aim of this research was to examine the effect of the hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple cultivar from central Italy (Mela Rosa dei Monti Sibillini) on CCl4-induced hepatotoxicity in rats. Phytoconstituents were determined by liquid chromatography–mass spectrometry (LC-MS) analysis showing an abundance of proanthocyanidins and flavonol derivatives together with the presence of annurcoic acid in APE. Wistar rats received APE/APP (30 mg/kg oral administration) for three days before CCl4 injection (2 mL/kg intraperitoneal once on the third day). Treatment with both APE and APP prior to CCl4 injection significantly decreased the serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) compared to the CCl4 group. Besides, pretreatment with APE reversed the CCl4 effects on superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) and interleukin-1beta (IL-1β) levels in liver tissue in rats and reduced tissue damage as shown in hematoxylin and eosin staining. These results showed that this ancient Italian apple is worthy of use in nutraceuticals and dietary supplements to prevent and/or protect against liver disorders.

It has been proposed carbon tetrachloride (CCl 4 ) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies.Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl 4 -induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl 4 (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed.Administration of PS with CCl 4 significantly inhibited alterations in the serum levels of AST, ALP ( ** P < 0.01), and ALT ( *** P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl 4 -induced hepatotoxicity in rats. K E Y W O R D Santioxidant, CCl 4 , hepatoprotective, liposome, phosphatidylserine

Cirrhotic cardiomyopathy is a critical factor that causes morbidity and mortality in crucial conditions such as liver transplantation. In animal model, the common pathophysiologic mechanisms of cirrhotic cardiomyopathy are similar to those associated with bile duct ligation (BDL). Overproduction of inflammatory and oxidant markers plays a crucial role in cirrhotic cardiomyopathy. Spermidine, a multifunctional polyamine, is known for its antioxidant and anti-inflammatory effects. In this study, we investigated the effects of spermidine on development of cirrhotic cardiomyopathy in BDL rats. Rats were randomly housed in 6 groups. Except the normal and sham groups, BDL was performed for all the control and spermidine groups. Seven days after operation, 3 different doses of spermidine (5, 10 and 50 mg/kg) were administrated until day 28, in spermidine groups. At the end of the fourth week, the electrocardiography (ECG) and papillary muscle isolation were performed. The serum level of tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), and IL-10 and cardiac level of superoxide dismutase, glutathione (GSH). and malondialdehyde (MDA) were assessed. Furthermore, the nuclear factor-κB (NF-κB) expression was assessed by western blot. Cardiac histopathological changes were monitored. The serum levels of magnesium (Mg2+) and potassium (K+) were investigated. Control group, exhibited exaggerated signs of cirrhotic cardiomyopathy in comparison with the sham group. Co-administration of spermidine at the dose of 10 mg/kg in BDL rats significantly improved the cardiac condition, reduced the inflammatory mediators, and increased antioxidant enzymes. In addition, the histopathologic findings were in accordance with the other results of the study. Besides, there was no significant alteration in serum levels of Mg2+ and K+. This study demonstrates that spermidine at the dose of 10 mg/kg significantly improved the cirrhotic cardiomyopathy in BDL model in rats.

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