Anticancer and antimicrobial evaluation of extract from brown algae Hormophysa cuneiformis.

AIM: We investigated the antimicrobial and anticancer properties of an ethanol crude extract of Red Sea brown alga (Hormophysa cuneiformis) from Egypt. METHODS: Extraction was achieved by mixing 100 g of sample powder with absolute ethanol, incubating at 37 °C overnight in a shaking incubator, and then collecting the extract. The extract's antimicrobial activity was tested using a well diffusion assay against the tested pathogens (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Candida albicans) in comparison to commercial antibiotics. Anticancer activity was assessed using MTT assay on MCF-7, HepG-2, and HEP-2 cell lines. The anticancer mechanism of action against the HepG-2 cell line was investigated using cell cycle analysis, Annexin V, and antioxidant enzymes, in addition to transmission electron microscopy. RESULTS: GC-MS phytoconstituent profile of the extract was dominant with fatty acids. A broad antimicrobial effect against all the pathogenic isolates of E. coli, S. aureus, B. subtitles, and C. albicans was demonstrated, especially at the high concentration in comparison to commercial antibiotics. The extract could inhibit the growth of the tested cell lines. We observed the most significant effect on HepG-2 cells, and the concentration of the extract played a role in the level of inhibition (IC50 of 44.6 ± 0.6 µg/ml). The extract had negligible effects on Vero normal cell lines at the lower concentration, with slight toxicity (90.8% viability) at the highest concentration (500 µg/ml). At this same concentration, the extract caused 80-92% inhibition of the cancer cell lines. The extract appears to have demonstrated promising effects on cancer cells. It induces programmed cell death (apoptosis), arrests the cell cycle, and affects the oxidative/antioxidant balance within the cells, potentially leading to the suppression or elimination of cancer cells. These findings are encouraging and may have implications for cancer treatment or further research in this area. More action of extract was seen against bacteria than fungi, with a wide antibacterial impact against all of the tested isolates, notably at the high concentration in comparison to conventional antibiotics. CONCLUSION: According to the findings, H. cuneiformis may be a valuable source of chemicals that are both antimicrobial and anticancer.

Effect of Saffron Extract on the Hepatotoxicity Induced by Copper Nanoparticles in Male Mice.

BACKGROUND: Nanotechnology application has widespread use in many products. Copper nanoparticles (CuNPs) are widely used in industrial applications. The present study was conducted to investigate the effect of the ethanolic saffron extract (ESE) as a natural antioxidant on the hepatotoxicity induced by CuNPs in male mice. METHODS: The characterization of CuNPs was determined using ultraviolet-visible absorption spectroscopy, particle size analysis, zeta potential, Fourier-transform infrared spectroscopy, and electron microscope. The effect of saffron on the hepatotoxicity induced by CuNPs in mice was evaluated by evaluating the survival rate of the mice, oxidative stress, antioxidant capacity, DNA evaluation, as well as its effect on the histology and transmission electron microscope of the liver. RESULTS: The results revealed that all parameters were affected in a dose-dependent manner by CuNPs. These effects have been improved when the treatment of CuNPs is combined with ethanolic saffron extract. CONCLUSIONS: We can conclude that saffron and its bioactive crocin portion can prevent CuNP-induced oxidative liver damage. This substance should be useful as a new pharmacological tool for oxidative stress prevention.

Anti-Diabetic and Anti-Adipogenic Effect of Harmine in High-Fat-Diet-Induced Diabetes in Mice.

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 Vitro and In Vivo Effects of Synthesis Novel Phenoxyacetamide Derivatives as Potent Apoptotic Inducer against HepG2 Cells through PARP-1 Inhibition.

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.

Biochemical, Histological, and Ultrastructural Studies of the Protective Role of Vitamin E on Cyclophosphamide-Induced Cardiotoxicity in Male Rats.

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.

Effect of Feeding Pomegranate (Punica granatum) Peel and Garlic (Allium sativum) on Antioxidant Status and Reproductive Efficiency of Female Rabbits.

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.

Nutraceutical Effect of Resveratrol on the Mammary Gland: Focusing on the NF-κb /Nrf2 Signaling Pathways.

The aim of this study is to evaluate the defensive role of resveratrol, which is antagonistic to the oxidative stress and inflammation that is prompted by LPS in mammary tissue of female mice. Thirty adult mice were distributed into three groups (n = 10) control (CON), lipopolysaccharides at 2.5 mg/kg (LPS), and lipopolysaccharides at 2.5 mg/kg with 2 mg/kg of resveratrol (RES + LPS). The treatments were applied for 15 consecutive days. Spectrophotometry was used to quantify ROS in the blood, and proinflammatory cytokines concentrations were determined through radioimmunoassay. NF-κB, Jnk, IL-1ß, Erk, IL-6, Nrf2 and TNF-α were quantified by RT-qPCR, and Western blots were used to quantifyP65 and pP65 protein intensities. MDA production was considerably increased, and the activity of T-AOC declined in the LPS treatment in comparison with the CON group but was significantly reversed in the RES + LPS group. Proinflammatory cytokines production and the genes responsible for inflammation and oxidative stress also showed higher mRNA and pP65 protein intensity in the LPS group, while Nrf2 showed a remarkable decline in mRNA expression in the LPS versus the CON group. All these mRNA intensities were reversed in the RES + LPS group. There were no remarkable changes in P65 protein intensity observed between the CON, LPS, and RES + LPS groups. In conclusion, resveratrol acts as a protective agent to modulate cellular inflammation and oxidative stress caused by LPS in mammary tissue of female mice.

Possible Ameliorative Effects of the Royal Jelly on Hepatotoxicity and Oxidative Stress Induced by Molybdenum Nanoparticles and/or Cadmium Chloride in Male Rats.

The present study aimed to investigate the effect of the royal jelly (RJ) on hepatotoxicity induced by molybdenum nanoparticles (MoO3-NPs), cadmium chloride (CdCl2), or their combination in male rats at biochemical, inflammation, immune response, histological, and ultrastructural levels. The physicochemical properties of MoO3-NPs have been characterized, as well as their ultrastructural organization. A rat experimental model was employed to assess the liver toxicity of MoO3-NPs, even in combination with CdCl2. Different cellular studies indicate divergent mechanisms, from increased reactive oxygen species production to antioxidative damage and cytoprotective activity. Seventy male rats were allocated to groups: (i) control; (ii) MoO3-NPs (500 mg/kg); (iii) CdCl2 (6.5 mg/kg); (iv) RJ (85 mg/kg diluted in saline); (v) MoO3-NPs followed by RJ (30 min after the MoO3-NPs dose); (vi) CdCl2 followed by RJ; and (vii) a combination of MoO3-NPs and CdCl2, followed by RJ, for a total of 30 successive days. Hepatic functions, lipid profile, inflammation marker (CRP), antioxidant biomarkers (SOD, CAT, GPx, and MDA), and genotoxicity were examined. Histological changes, an immunological marker for caspase-3, and transmission electron microscope variations in the liver were also investigated to indicate liver status. The results showed that RJ alleviated the hepatotoxicity of MoO3-NPs and/or CdCl2 by improving all hepatic vitality markers. In conclusion, the RJ was more potent and effective as an antioxidant over the oxidative damage induced by the combination of MoO3-NPs and CdCl2.

Mechanisms and histopathological impacts of acetamiprid and azoxystrobin in male rats.

Acetamiprid (neonicotinoid insecticide) and azoxystrobin (fungicide) are widespread pesticides used for pest management, but they have the potential for toxicity to mammals. The goal of this study was to look for oxidative stress, metabolic alterations, and reproductive problems in male rats' serum after 2 months of exposure to sub-lethal dosages of acetamiprid and azoxystrobin. Seven classes of male rats were formed: control, 3 groups of acetamiprid (1/10, 1/20, 1/40 LD50), and 3 groups of azoxystrobin (1/10, 1/20, 1/40 LD50) and were orally daily treated (n = 8/group). Our findings revealed that acetamiprid and azoxystrobin disrupted oxidative and metabolic processes in the examined rats throughout 30 and 60 days of testing. The levels of nitric oxide increased significantly, while catalase, a superoxide dismutase enzyme, and glutathione reductase activity were reduced. Serum levels of sex hormones, calcium, and total protein have all dropped substantially in rats. In comparison to the control group, the testis and liver structure, as well as spermatozoa parameters, had distinct histological characteristics. In conclusion, acetamiprid and azoxystrobin exhibit dose- and time-dependent effects on oxidative parameters that cause testis damage.

Evaluation of acetamiprid and azoxystrobin residues and their hormonal disrupting effects on male rats using liquid chromatography-tandem mass spectrometry.

Endocrine-disrupting compounds as pesticides affect the hormonal balance, and this can result in several diseases. Therefore, the analysis of representative hormones with acetamiprid (AC) and azoxystrobin (AZ) was a good strategy for the investigation of the endocrine-disrupting activity of pesticides. Hence, a sensitive and rapid analytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The method was validated for the analysis of AC, AZ, estriol, estrone, progesterone, and testosterone in the serum, testis, and liver of rats. The correlation between the residues of pesticides and the disturbance of the endocrine system was evaluated. The different mass parameters, mobile phase types, analytical columns, injection volumes, and extraction solvents were compared to get the lowest limit of detection of the studied compounds. The detection limits of AC, AZ, estriol, estrone, progesterone, and testosterone were 0.05, 0.05, 1.0, 10, and 1.0 ng/ml, respectively. The method developed was applied to evaluate the changes in these hormones induced by the duration of exposure to AC and AZ in rat testis and serum. The hormones level in rat serum and testis had a significant decrease as they were oral gavage treated with different high concentrations of studied pesticides. Both pesticides were distributed in the body of rats by the multi-compartment model (liver, testis, and serum).

Effect of l-carnitine on aspartame-induced oxidative stress, histopathological changes, and genotoxicity in liver of male rats.

Background Aspartame (ASP) is used for treatment of obesity and diabetes mellitus. This study was designed to illustrate the biochemical responses and histopathological alterations besides the genotoxicity of ASP alone or with l-carnitine (LC) in the liver of rats. Methods Animals were separated into six groups: control, lower dose of ASP (ASP-LD; 75 mg/kg), higher dose of ASP (ASP-HD; 150 mg/kg), l-carnitine (LC; 10 mg/kg), ASP-LD plus LC, and ASP-HD plus LC. Treatment was carried out orally for 30 consecutive days. Results ASP raised the activity of some enzymes of liver markers and disturbed the lipid profile levels. The hepatic reduced glutathione (GSH) levels, the marker enzymes of antioxidant activities, were obviously diminished, and, possibly, the lipid peroxidation, C-reactive protein, and interleukins levels were increased. ASP significantly increased the DNA deterioration in comparison with the control in a dose-dependent manner. LC prevented ASP-induced liver damage as demonstrated by the enhancement of all the above parameters. Results of histopathological and electron microscopic examination proved the biochemical feedback and the improved LC effect on liver toxicity. Conclusions The co-treatment of LC showed different improvement mechanisms against ASP-induced liver impairment. So, the intake of ASP should be regulated and taken with LC when it is consumed in different foods or drinks to decrease its oxidative stress, histopathology, and genotoxicity of liver.

Evaluation of the Effect of Nanoparticles Zinc Oxide/Camellia sinensis Complex on the Kidney of Rats Treated with Monosodium Glutamate: Antioxidant and Histological Approaches.

BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are robustly used biomedicine. Moreover, no study has been conducted to explore the consequence of green synthesis of ZnO NPs with Camellia sinensis (green tea extract, GTE) on kidneys of rats treated with monosodium glutamate (MSG). METHODS: Therefore, the objective of the research was designed to explore the possible defensive effect of GTE/ZnO NPs against MSG-induced renal stress investigated at redox and histopathological points. RESULTS: The levels of urea and creatinine increased as the effect of a high dose of MSG, in addition, the myeloperoxidase and xanthine oxidase activates were elevated significantly with the high dose of MSG. The levels of non-enzymatic antioxidants (uric acid, glutathione, and thiol) were decreased sharply in MSG-treated rats as compared to the normal group. CONCLUSION: The data displayed that GTE/ZnO NPs reduced the effects of MSG significantly by reduction of the level peroxidation and enhancement intracellular antioxidant. These biochemical findings were supported by histopathology evaluation, which showed minor morphological changes in the kidneys of rats.

Role of L-carnitine in protection against the cardiac oxidative stress induced by aspartame in Wistar albino rats.

Aspartame (ASP) has been used as an alternative to sucrose for diabetics and obese people worldwide. Co-administration of L-carnitine (LC) with ASP has a protective effect against the liver and kidney toxicity induced of ASP. The goal of the investigation was to assess the enhancement of LC effect on the cardiac toxicity caused of ASP. The rats were divided into 6 groups: control with saline, LC (10 mg/kg), ASP (75 mg/kg), ASP (150 mg/kg), LC with 75 mg/kg of ASP, and LC with 150 mg/kg ASP. The antioxidants were determined by measuring the activities of myeloperoxidase, xanthine oxidase, superoxide dismutase, catalase, and glutathione peroxidase, and by assessing the levels of lipid peroxidation, total thiols, and glutathione. There was a significant elevation in LPO, in conjunction with a significant decline in the enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase and the non-enzymatic antioxidants glutathione and thiols. The cardiac myofibrils were found in a disarrayed pattern in ASP treated-animals as compared to the control rats. The animals treated with ASP-HD showed more than one apoptotic cell with a large tail and a small head, and the relaxed loops of the damaged DNA were extended to form a comet-shaped structure. These effects may be due to the excessive generation of reactive oxygen species by ASP, which reduces cardiac function. Co-administration of LC with ASP improved all of the above-mentioned parameters that were disrupted of ASP alone. This study evidences a sufficient originality in showing how LC plays a positive role against cardiac toxicity of ASP.