Doxorubicin (DOX) is one of the most important anticancer agents used in treating breast cancer. However, chronic cardiotoxicity and multidrug resistance limit the chemotherapeutic use of DOX. This study aimed to evaluate the capability of calcium channel blocker diltiazem (DIL) to reverse DOX resistance in breast cancer MCF-7 cells and to confer protection against DOX-induced cardiotoxicity in Wistar rats. For this purpose, we explored the effects of DOX on cell cycle phase distribution and expression of ABCB1, FOXO3a, and p53 genes in the presence and absence of DIL (20 μg/ml) and studied the ability of DIL to prevent DOX-induced cardiotoxicity after a single injection of DOX (15 mg/kg) in male Wister rats. We found that compared with DOX alone treatment, DIL + DOX treatment down regulated the ABCB1 gene expression by > fourfold but up regulated the FOXO3a and p53 genes expression by 1.5 fold. DIL treatment conferred protection against DOX-induced cardiotoxicity, as indicated by a decrease in the levels of the cardiac enzyme creatine kinase MB and malondialdehyde and an increase in the total antioxidant capacity and glutathione peroxidase levels. These biochemical results were further confirmed by the histopathological investigation of cardiac cells, which showed normal cardiac cells with central vesicular nuclei and prevention of DOX-induced disruption of normal cardiac architecture in the DIL to DOX group. Taken together, our results indicate that DIL treatment can reverse the resistance of breast cancer cells to the therapeutic effects of DOX and can protect against DOX-induced cardiotoxicity in rats.

Patients suffering from Alzheimer’s disease (AD) are still increasing worldwide. The development of (AD) is related to oxidative stress and genetic factors. This study investigated the therapeutic effects of ellagic acid (EA) on the entorhinal cortex (ERC), which plays a major role in episodic memory, in the brains of an AD rat model. AD was induced using AlCl₃ (50 mg/kg orally for 4 weeks). Rats were divided into four groups: control, AD model, EA (treated with 50 mg/kg EA orally for 4 weeks), and ADEA (AD rats treated with EA after AlCl₃ was stopped) groups. All rats were investigated for episodic memory using the novel object recognition test (NORT), antioxidant serum biomarkers, lipid peroxidation, histopathology of the ERC, and quantitative PCR for the superoxide dismutase (SOD) gene. EA therapy in AD rats significantly increased the discrimination index for NORT and the levels of SOD, glutathione, and total antioxidant capacity. Lipid peroxidation products were decreased, and the neurofibrillary tangles and neuritic plaques in the ERC sections were reduced after EA administration. The decrease in ERC thickness in the AD group, caused by caspase-3-mediated apoptosis and neurotoxicity due to amyloid precursor protein, was modulated by the increased SOD mRNA expression. Adjustment of the ERC antioxidant environment and decreased oxidative stress under EA administration enhanced SOD expression, resulting in the modulation of amyloid precursor protein toxicity and caspase-3-mediated apoptosis, thereby restoring episodic memory.

Introduction. Spinal cord injury (SCI) is a life-disrupting condition in which the first few days are the most critical. Secondary conditions remain the main causes of death for people with SCI. The response of different cell types to SCI and their role at different times in the progression of secondary degeneration are not well understood. The aim of this study was to study the histopathological changes of compressed spinal cord injury (CSCI) in a rat model. Material and methods. Forty adult male Sprague-Dawley rats were divided into four groups. In group I, the rats were left without any surgical intervention (control). In group II, the rats were subjected to laminectomy without spinal cord compression (sham-operated). In group III, the rats were sacrificed one day after CSCI. In group IV, the rats were sacrificed seven days after CSCI. The light microscopy was employed to study the morphology using H&E, osmic acid staining and immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The electron microscopy was applied for ultrastructure study. Results. Histopathological examination of the posterior funiculus of the white matter revealed minute hemorrhages and localized necrotic areas on day 1, which transformed to areas of cavitation and fibrinoid necrosis surrounded by a demarcating rim of numerous astrocytes by day 7. The mean percentage of area of GFAP expression increased significantly by day 7. Osmic acid staining revealed swollen nerve fibers after one day, while numerous fibers had been lost by day 7. An ultrastructure study revealed swollen redundant thinned myelin and myelin splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the myelin sheath were folded and wrinkled with partial or complete demyelination areas. The myelin lamellae were disorganized and loose. The G-ratio was significantly greater on day 1 than day 7 after CSCI. Conclusions. In the rat model of CSCI details of the progressive spinal cord injury can be analyzed by morphological methods and may be helpful in the identification of the onset and type of clinical intervention. Introduction. Spinal cord injury (SCI) is a life-disrupting condition in which the first few days are the most critical. Secondary conditions remain the main causes of death for people with SCI. The response of different cell types to SCI and their role at different times in the progression of secondary degeneration are not well understood. The aim of this study was to study the histopathological changes of compressed spinal cord injury (CSCI) in a rat model. Material and methods. Forty adult male Sprague-Dawley rats were divided into four groups. In group I, the rats were left without any surgical intervention (control). In group II, the rats were subjected to laminectomy without spinal cord compression (sham-operated). In group III, the rats were sacrificed one day after CSCI. In group IV, the rats were sacrificed seven days after CSCI. The light microscopy was employed to study the morphology using H&E, osmic acid staining and immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The electron microscopy was applied for ultrastructure study. Results. Histopathological examination of the posterior funiculus of the white matter revealed minute hemorrhages and localized necrotic areas on day 1, which transformed to areas of cavitation and fibrinoid necrosis surrounded by a demarcating rim of numerous astrocytes by day 7. The mean percentage of area of GFAP expression increased significantly by day 7. Osmic acid staining revealed swollen nerve fibers after one day, while numerous fibers had been lost by day 7. An ultrastructure study revealed swollen redundant thinned myelin and myelin splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the myelin sheath were folded and wrinkled with partial or complete demyelination areas. The myelin lamellae were disorganized and loose. The G-ratio was significantly greater on day 1 than day 7 after CSCI. Conclusions. In the rat model of CSCI details of the progressive spinal cord injury can be analyzed by morphological methods and may be helpful in the identification of the onset and type of clinical intervention.

The resistance to therapy and relapse in hepatocellular carcinoma (HCC) is highly attributed to hepatic cancer stem cells (HCSCs). HCSCs are under microenvironment control. This work aimed to assess the systemic effect of ellagic acid (EA) on the HCC microenvironment to decline HCSCs. Fifty Wistar rats were divided into six groups: negative control (CON), groups 2 and 3 for solvents (DMSO), and (OVO). Group 4 was administered EA only. The (HCC-M) group, utilized as an HCC model, administered CCL4 (0.5 mL/kg in OVO) 1:1 v/v, i.p) for 16 weeks. HCC-M rats were treated orally with EA (EA + HCC) 50 mg/kg bw for five weeks. Biochemical, morphological, histopathological, and immunohistochemical studies, and gene analysis using qRT-PCR were applied. Results revealed elevated liver injury biomarkers ALT, AST, ALP, and tumor biomarkers AFP and GGT, and marked nodularity of livers of HCC-M. EA effectively reduced the biomarkers and restored the altered structure of the livers. At the mRNA level, EA downregulated the expression of TGF-α, TGF-β, and VEGF, and restored p53 expression. This induced an increase in apoptotic cells immunostained with caspase3 and decreased the CD44 immunostained HCSCs. EA could modulate the tumor microenvironment in the HCC rat model and ultimately target the HCSCs.

Background: Aflatoxin (AF), a metabolite of Aspergillus flavus, is injurious to vital body organs. The bacterial defense against such mycotoxins has attracted significant attention. Lactic acid bacteria (LAB) are known to ameliorate AF toxicity. Methods: Thirty adult male rats were divided into six groups (five each) to perform the experiments. The control (Co) group was fed a basal diet and water. Each of the following periods lasted 21 days: the milk (MK) group orally received milk (500 µL); LAB suspension (500 µL) containing 10⁷ cfu/mL was orally provided to the LAB group; AF (0.5 mg/kg) was orally given to the AF group; and a combination of AF and LAB was administered to the AF + LAB group. The AF/LAB group was initially given AF for 21 days, followed by LAB for the same period. Finally, the rats were dissected to retrieve blood and tissue samples for hematological, biochemical, and histological studies. Results: The results revealed a significant decrease in RBCs, lymphocytes, total proteins, eosinophil count, albumin, and uric acid, whereas the levels of WBCs, monocytes, neutrophils, creatinine, urea, aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase, and creatinine kinase significantly increased in the AF group in comparison to the control group. The histological examination of the AF group revealed necrosis and apoptosis of the kidney’s glomeruli and renal tubules, nuclei vacuolization and apoptosis of hepatocytes, congestion of the liver’s dilated portal vein, lymphoid depletion in the white pulp, localized hemorrhages, hemosiderin pigment deposition in the spleen, and vacuolization of seminiferous tubules with a complete loss of testis spermatogenic cells. Meanwhile, protective and therapeutic LAB administration in AF-treated rats improved the hematological, biochemical, and histological changes. Conclusions: The study revealed LAB-based amelioration to AFB1-induced disruptions of the kidney, liver, spleen, and testis by inhibiting tissue damage. The therapeutic effects of LAB were comparatively more pronounced than the protective effects.