Background: Natural compounds such as fisetin have promising in breast cancer treatment, but their poor pharmacokinetics limit their therapeutic application. This study utilized a synergistic approach by combining fisetin-loaded Nigella sativa (N.S.) oil nanovesicles (FIS-NSs) and carbohydrate-based microneedles (FIS-NSs-MNs) to improve breast cancer management. Methods: Chemical composition of NS petroleum ether extract using gas chromatography–mass spectrometry (GC/MS). FIS-NSs were prepared and characterized for particle size, polydispersity, zeta potential, encapsulation efficiency, and stability. These vesicles were embedded into gelatin, hyaluronic acid, and carboxymethyl cellulose microneedles. In vitro drug release, ex vivo permeation, cytotoxicity against breast cancer cells, and in vivo antitumor efficacy in Ehrlich tumor models were evaluated. Results: Optimized FIS-NSs displayed nanoscale size (190 ± 0.74 nm), low P.D.I (0.25 ± 0.07), high surface charge (+37 ± 0.57 mV), and high encapsulation (88 ± 0.77%). In vitro investigations showed sustained FIS release (~85% over 72 h), while ex vivo permeation showed higher absorption than free fisetin. Both FIS-NSs and FIS-NSs-MNs showed dose-dependent cytotoxicity against breast cancer cells, with lower IC₅₀ than free fisetin (24.7 µM). In vivo, FIS-NSs-MNs and tumor burden inhibition (~77%), reduced oxidative stress (54%), restored antioxidant defenses, and decreased inflammatory markers. Immunohistochemical analysis for caspase-3 showed apoptosis activation within tumor tissues. Conclusions: These findings demonstrate that FIS administration via NS-MNs improves drug stability, penetration, and apoptotic activity, resulting in enhanced anticancer effects. This innovative nanovesicle–microneedle platform provides a non-invasive, effective, and patient-friendly approach for the effective treatment of breast cancer, with potential for broader applications in oncological nanomedicine.

Melatonin (MEL) has potent antioxidant and tissue-protective effects against oxidative stress, so it attracted scientific attention. This study evaluated the effects of MEL on acute pancreatitis (AP) in male rats. Blood samples were collected for assessment of lipid profile, amylase, and lipase activity. Inflammatory cytokines, caspase-3, lipid peroxidation products (MDA), as well as the levels of the antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), were measured in pancreatic tissue. AP was proven by histopathological evaluation and by serum elevation of amylase and lipase enzymes. MEL significantly minimized histological alterations of AP, diminished serum amylase, and lipase activity, and improved lipid profile. MEL dramatically reduced MDA levels, stopped the onset of oxidative stress, and maintained SOD, CAT, GPx, and GSH levels in the pancreas of AP rats demonstrating its antioxidant capacity. Additionally, MEL halted the rise in pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. Furthermore, MEL enhanced the anti-inflammatory cytokine IL-10 indicating its anti-inflammatory effect. Finally, it played a cytoprotective role by preventing apoptosis through decreasing elevated levels of caspase-3 and keeping cell viability. In conclusion, MEL has protective effects on the pancreas which are attributed to its anti-hyperlipidemic, antioxidant, and anti-apoptotic effects as well as its anti-inflammatory properties.

The present work was designed to investigate the effect of aminoguanidine (AMG) on methotrexate (MTX)- induced lung toxicity in rats. Forty adult male rats weighing 200–220 gm divided into four groups, 10 each were used in the study. The control group received normal saline. AMG-treated group: rats received 50 mg/kg/day AMG. Whereas the MTX-treated group: rats received 0.5 mg/kg MTX twice weekly, and AMG+MTX-treated group: rats were co-administered AMG and MTX at the same doses as in the previous groups. All groups received their treatment via the IP route. Additionally, the experiment duration was 4 weeks. MTX administration revealed a significant decrease in SOD, CAT, GSH, Nrf2, and Bcl-2 accompanied by a significant increase in MDA, NO, IL-6, IL-1β, NF-κB, caspase-3, and Bax compared to the control group. Moreover, there were histological abnormalities in the lung tissue. However, the AMG+MTX-treated group produced a significant increase in SOD, CAT, GSH, Nrf2, and Bcl-2, and a significant decrease in MDA, NO, IL-6, IL-1β, NF-κB, caspase-3, and Bax compared to the MTX-treated group. Besides, the histological results strongly supported our biochemical findings. The present study demonstrated the protective effect of AMG against MTX- induced lung toxicity in rats through its antioxidant, anti-inflammatory, and anti-apoptotic actions.

This research aims to explore if curcumin (CUR) can protect male albino rats from diclofenac (DIC) sodium-induced hepatotoxicity. The adult male Albino rats were divided into four groups (n=8) in this study. Control group: corn oil (i.p.) was given every day for seven days. CUR-treated group: was given CUR (200 mg/kg, i.p) every day for seven days. DIC-treated group: was given corn oil (i.p.) every day for seven days, followed by DIC single dose (150 mg/kg, i.p) 2 hours after last corn oil injection. DIC+CUR-treated group: was given CUR (200 mg/kg i.p.) every day for seven days followed by DIC single dose (150 mg/kg, i.p) two hours following the last CUR injection. Animals were sacrificed twenty-four hours following the last treatment. Blood serum was collected and tested for liver function markers. The liver was removed and used for biochemical and light microscopic examinations. The data showed that serum AST, ALT levels, as well as hepatic MDA, NO, and TNFα levels were significantly higher in the DIC-treated group than in the control group. While, serum total protein and albumin levels, as well as hepatic SOD levels, were significantly reduced. In contrast to the DIC-treated group, pretreatment with CUR resulted in a significant decrease in AST, ALT, MDA, NO, and TNFα as well as a significant increase in total protein, albumin, and SOD levels. CUR pretreatment also ameliorated the histological alterations. In conclusion, CUR treatment provided excellent protection against DIC-induced liver toxicity and oxidative damage in rats.

This research aims to investigate the potential antidepressant properties of atorvastatin (ATV), fenofibrate (FFB) and their combination and compare them with fluoxetine (FLX) in the chronic mild stress (CMS) model of depression. Adult male wistar rats were assigned at random into 6 groups (n=8). Control group: received Dimethyl sulfoxide (DMSO 0.5%. p.o). CMS-group: received (DMSO 0.5%. p.o). FLX-treated group: received FLX (10 mg/kg/day. p.o). ATV-treated group: received ATV (10 mg/kg/day. p.o). FFB-treated group: received FFB (200 mg/kg/day. p.o). ATV+FFB-treated group: received combination of ATV and FFB. All groups received treatments 24hrs, 5 hrs and 1 h before OFT and AFST. Then after a 14-day washout period, all groups were given the same treatments and exposed to CMS (except control group) for 3 successive weeks. One hour after the last dose, OFT and CFST were conducted. The data showed that the immobility time in CFST, brain MDA, and IL6 levels were significantly elevated in the CMS group than in the control group. While, brain SOD, BDNF, SE and DA levels, were significantly reduced. In contrast to the CMS group, treatment with FLX, ATV, FFB and the combination of ATV and FFB resulted in a significant reduction in immobility time, MDA, and IL6 levels, as well as a significant increase in SOD, BDNF, SE and DA levels except FFB group that showed non-significant difference with CMS group in DA level. In conclusion, ATV, FFB and their combination presented antidepressant-like effect in CMS-induced depression in male rats.

The objective of this study was to clarify the ameliorative effect of metformin (MET), carvedilol (CAR), and their combination and the underlying mechanisms in a non-diabetic rat model of isoprenaline (ISO)-induced MI. The adult male Wistar rats were allocated into six groups (n=8). Control group A received saline while control group B received DMSO 0.5% (i.p) for 10 days. ISO-treated group: received ISO (85 mg/kg.i.p.) on the first and second day of the experiment with the injection of normal saline for 10 days from the first day. ISO+MET and ISO+CAR-treated groups: received ISO as previously described and MET (200 mg/kg.i.p.) and CAR (10 mg/kg.i.p.) respectively for 10 days from the first day of the experiment. ISO+MET+CAR-treated group: received ISO, MET, and CAR as previously described. In the ISO group, the rise in serum cardiac biomarkers cTn-I and LDH provided evidence of MI. In addition, cardiac MDA, IL6, caspase-3, and Bax gene levels were significantly elevated, while cardiac SOD, GSH, pAMPK, eNOS, Bcl-2 gene, and Bcl-2/Bax ratio levels were significantly reduced with histopathological changes in cardiac tissue. Whereas posttreatment with MET, CAR, and their combination significantly reversed these overwhelming ISO-induced damaging effects on the heart. In conclusion, MET, CAR, and their combination could improve myocardial injury in ISO-induced MI through AMPK signaling pathway activation, and anti-apoptotic, anti-inflammatory, and antioxidant mechanisms. Subsequently, promote the recovery of cardiomyocyte function.