Background: Cyclophosphamide (CP) (Cytoxan or Endoxan) is an efficient anti-tumor agent, widely used for the treatment of various neoplastic diseases. The study aimed to investigate the protective role of vitamin E (vit E) in improving cardiotoxicity in rats induced by CP. Materials and methods: Forty male Wistar rats were divided randomly into four experimental groups (each consisting of ten rats); the control group was treated with saline. The other three groups were treated with vit E, CP, and the combination of vit E and CP. Serum lipid profiles, enzyme cardiac biomarkers, and cardiac tissue antioxidants were evaluated, as well as histological and ultrastructure investigations. Results: CP-treated rats showed a significant increase in serum levels of cardiac markers (troponin, CK, LDH, AST, and ALT), lipid profiles, a reduction in the antioxidant enzyme activities (CAT, SOD, and GPx), and an elevation in the level of lipid peroxidation (LPO). The increase in the levels of troponin, LDH, AST, ALP, and triglycerides is a predominant indicator of cardiac damage due to the toxic effect of CP. The biochemical changes parallel cardiac injuries such as myocardial infarction, myocarditis, and heart failure. Vitamin E played a pivotal role, as it attenuated most of these changes because of its ability to scavenge free radicals and reduce LPO. In addition, vit E was found to improve the histopathological alterations caused by CP where no evidence of damage was observed in the cardiac architecture, and the cardiac fibers had regained their normal structure with minimal hemorrhage. Conclusions: As a result of its antioxidant activity and its stabilizing impact on the cardiomyocyte membranes, vit E is recommended as a potential candidate in decreasing the damaging effects of CP.

Diabetes mellitus (DM) causes an imbalance in the oxidative status of the human body. Three novel Dapagliflozin (Dapg) Zn (II), Cr (III) and Se (IV) complexes were prepared and characterized by elemental analysis, IR, electronic spectra, magnetic susceptibility, scanning electron microscopy (SEM) and X-ray diffraction. The molar conductance values confirmed the non-electrolytic nature of the Dapg complexes. According to spectral data, Dapg acts as a bidentate ligand. The thermal analyses of the complexes were studied using the DSC technique. The surface morphology and particle sizes of the Dapg complexes were investigated using SEM and XRD. XRD confirmed the crystalline structure for the complexity. This study investigated the effect of novel metal complexes of Dapg with the metals Zn (II), Cr (III) and Se (IV) on oxidative injury and tissue damage in the hepatic tissue of streptozotocin (STZ)-induced diabetic male rats. DM was experimentally induced in male rats. The diabetic rats received Dapg, Dapg/Zn, Dapg/Cr and Dapg/Se orally for 30 successive days. Male rats exposed to STZ showed multi-histopathological alterations in their hepatic tissue, including inflammatory and structural changes. STZ elevated oxidative stress markers in the hepatic tissue and lowered the antioxidant defense enzymes. Supplementation of Dapg with Zn, Cr or Se novel complexes significantly prevented hepatic injury and suppressed the generation of reactive oxygen species. The Dapg/Zn complex was highly effective against Bacillus subtilis and Streptococcus penumonia, while Dapg/Cr was highly effective against Escherichia coli and Pseudomonas aeruginosa, and Dapg/Se was highly effective against Staphylococcus aureas. In conclusion, Dapg novel metal complexes with Zn, Cr or Se protect against oxidative injury and the pathophysiological and bacterial complications of DM and hepatic tissue injury. The Dapg novel metal complexes improved hepatic functions, reduced blood glucose levels and enhanced the levels of antioxidant defense enzymes in diabetic male rats.

One of the most important health issues facing the world today is obesity. It is an important independent risk factor for developing type 2 diabetes. Harmine offers various pharmacological effects, such as anti-inflammatory and anti-tumor effects. The current study aims to investigate Harmine’s anti-diabetic and anti-adipogenic properties in albino mice after inducing low-grade inflammation with a high-fat diet (HFD). About forty-eight male albino mice were divided into four groups. Group 1: control mice were injected with daily saline and fed a normal chow diet of 21% protein for 5 months. Group 2: mice were treated daily with IP-injected Harmine (30 mg/kg body weight) and were fed a normal chow diet for 5 months. Group 3: mice were fed HFD to induce type 2 Diabetes Mellitus (T2DM) for 5 months. Group 4: mice were fed HFD for 14 weeks and treated with Harmine for the last 6 weeks. A figh-fat diet caused a significant increase in body and organ weight, lipid profiles, and destructive changes within the pancreas, kidney, and liver tissue. The administration of Harmine led to a remarkable improvement in the histological and ultrastructural changes induced by HFD. The findings indicate that mice cured using Harmine had lower oxidative stress, a higher total antioxidant capacity, and a reduced lipid profile compared to HFD mice. Harmine led to the hepatocytes partly restoring their ordinary configuration. Furthermore, it was noticed that the pathological incidence of damage in the structure of both the kidney and pancreas sections reduced in comparison with the diabetic group. Additional research will be required to fully understand Harmine and its preventive effects on the two forms of diabetes.

In the current investigation, Annona muricata Linn. lyophilized fruit pulp powder was evaluated for its hepatoprotective activity induced by paracetamol or acetaminophen (APAP). Male Sprague Dawley rats were orally pre-treated for 15 days with A. muricata lyophilized fruit pulp powder at low (1 g/kg b.wt) and high doses (2 g/kg b.wt). Silymarin (100 mg/kg) was administered as the standard drug. Hepatotoxicity was induced using APAP, in a single oral administration of 2.5 g/kg body weight dosage on the 15th day. Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were elevated in the APAP group but were found to be significantly reduced in the pre-treated groups in a dose-dependent manner. APAP administration brought down the serum total protein and albumin levels significantly. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were reduced in the APAP administration; further, the reduced glutathione pool in the tissue was also diminished significantly. However, with the administration of Annona lyophilized fruit pulp powder, the level of antioxidant parameters was near normal. A significant increase in lipid peroxidation was observed in the APAP group, while the silymarin, AML, and AMH groups exhibited resistance to lipid peroxidation (LPO), as evident from lower levels of LPO generated. Histopathological examination also revealed considerable tissue damage in the APAP alone treatment group, which was not devastating in the silymarin, AML, and AMH groups. Altogether, the study concludes that the lyophilized fruit pulp of A. muricata is protective against APAP-induced liver injury in rats by modulating the hepatic redox systems.

Egypt’s animal protein shortfall cannot be overcome by expanding the production of large animals alone, but rather by increasing the production of highly reproducing animals in the livestock unit. The goal of this study was to examine how adding pomegranate peel (PP), garlic powder (GP), or a mixture of the two to the diet of does affect their weight, the number of offspring, reproductive performance, hematological indices, and several antioxidants indicators as well as the liver and kidney functions. A total of 20 adult and mature female mixed rabbits at age 4.5–5 months and averaging 3.05 ± 0.63 kg body weight, were allocated into four experimental groups (n = 5). The first group was provided with the basal diet and was considered as control animals, while the second, third, and fourth groups were fed the basal diet supplemented with PP 3.0%, GP 3.0%, and a mixture of PP 1.5% + GP 1.5%, respectively. After 2 weeks of feeding the experimental diets, natural mating with untreated bucks was carried out. The kits were weighed immediately after parturition, and then every week. The study found that rabbits fed with 3% PP led to a 28.5% increase in the number of kits at birth compared to the control group. As an effect of supplementing PP 3%, GP 3%, and PP 1.5% + GP 1.5%, the birth weight increased by 9.2%, 7.2%, and 10.6%, respectively, as compared to the control. Hemoglobin increased significantly in all treatment groups as compared to the control at the age of kit weaning. Lymph cells increased significantly in the rabbits that were fed with GP (3%) than in other groups and even the control. The results showed that creatinine levels were significantly decreased in the PP (3%) and GP (3%) than in control rabbits. The level of triglycerides significantly declines in groups treated with PP (3%) than in other treatment groups and the control. The addition of PP 3% or GP 3% increased the progesterone hormone. The addition of PP 1.5% + GP 1.5% improved the immunoglobulin IgG. The results of superoxide dismutase, catalase, glutathione, and total antioxidant capacity showed a significant decline in groups treated with GP (3%) than other treated groups. In conclusion, pomegranate is a promising substance to include in a rabbit’s diet, followed by garlic to boost reproductive efficiency.

To discover potential cytotoxic agents, new semi-synthetic phenoxy acetamide derivatives, compound I and compound II, were synthesized, characterized, and screened for their cytotoxic activity against breast cancer (MCF-7) and liver cancer (HepG2) cell lines. The two compounds were more promising against HepG2 than the MCF-7 cell line according to IC₅₀ values. When tested against the HepG2 cell line, compound I, and compound II both had significantly increased cytotoxic activity when compared to the reference medication 5-Fluorouracil (5-FU), with IC₅₀ values of 1.43 M, 5.32 M, and 6.52 M for compound 1, 5-FU and compound II, respectively. Also, compound I displayed a degree of selectivity towards cancer cells compared to normal cells. Compound I significantly enhanced HepG2 total apoptotic cell death by about a 24.51-fold increase. According to cell cycle analysis, compound I induced the arrest of the cell cycle phases G1/S and blocked the progression of the HepG2 cells. Applying the RT-PCR technique achieved a highly significant upregulation in pro-apoptotic genes. The anti-apoptotic gene was significantly downregulated. There was an intrinsic and extrinsic pathway, but the intrinsic pathway was the dominant one. Tumor growth suppression as measured by tumor weight and volume and other hematological, biochemical, and histopathological analyses confirmed the efficacy of compound I as an anticancer agent in vivo examination. Finally, the molecular docking study revealed that compound I was properly docked inside the binding site of PARP-1 protein with stable binding energies and interactive binding modes. Therefore, compound I shows promise as a selective anti-cancer derivative for the treatment of liver cancer after more investigations and clinical studies. This selectivity is a favorable characteristic in the developing cytotoxic agents for cancer treatment, as it indicates a potential for reduced harm to health tissues.