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Abstract The recent research focuses on the use of natural products derived from plants in offering protection against the harmful effects of radiation. Reactive oxygen species (ROS) are the cause of certain diseases, such as cancer tumors, cardiovascular diseases, and liver dysfunction. Ionizing radiation passing through living tissues generates free radicals that can induce DNA damage. The damaging effects of ionizing radiation on DNA lead to cell death and are associated with an increased risk of cancer Ionizing radiation finds applications in many fields of the medical sciences and enhances the efficacy of diagnostic and therapeutic uses. Radiotherapy has been used as a treatment modality for cancer patients during their course of illness. Irradiation has associated side effects as it induces damage to normal tissue, resulting in acute and chronic toxicities or severe organ dysfunction. Hence, the need arises to protect human beings from the effects of radiation, even in a planned or unplanned accidental exposure. Even though the clinical application of ionizing radiation in radiotherapy and other medical areas is widely accepted and has accrued colossal success, the damage to the healthy surrounding tissues has limited its usage. Thus, there is an urgent need to develop drugs from plants and herbs that are cost-effective, readily available, and capable of scavenging free radicals, thus protecting normal cells during radiotherapy and reducing radiation’s harmful effect in an emergency radiation accident. This is the motivation for this work. Sargassum algae are potential sources of antioxidant agents such as polyphenols, including flavonoids and phenols, amino acids, fatty acids, and essential elements as well as other classes of secondary metabolites such as protein, proanthocyanidins, beta-carotene, and saponins, which are of high nutritional value and important to humans and animals. In this study we prepared nano metal complex of copper acetate with ahydrazide ligand and nano metal oxides of(ZnO, Fe2O3, and CuO )at a concentration of 10 μM with seaweed Sargassum vulgare nano methanolic extract at a concentration of 4 g/kg body weight of the rat. Also, we studied the characterization of these nanoparticles by using different techniques like X-Ray diffraction analysis (XRD), scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectra (DRS), and energy dispersive X-ray (EDX). The present study has been carried out in order to access the radioprotective efficiency role and the antioxidant effect of natural biochemical ingredients present in different groups of rat treated with Sargassum vulgare extract loaded on nano metal particles (ZnO, Fe2O3, [Cu(OAC)2 (HL)2]complex and CuO) against oxidative stress and liver tissue injury in the gamma-irradiation (6 Gy)-treated group of rats. Algal sampling, identification and extraction Specimens of the brown seaweed Sargassum vulgare (Fucales, Phaeophyta) were collected on October 2021 from the littoral zone of rocky shorelines in Hurghada city (27° 15′ 58.45″ N, 33° 48′ 57.09″ E), the Red Sea coast of Egypt. it is one of the most important places of interest for algal growth in Egypt (intertidal zone). Metabolomic profiling and antioxidant properties of Sargassum vulgare Polyphenol fractions (flavonoids and phenolics), phytochemical constituents (proanthocyanidins, saponins, β-carotene, and protein), antioxidant capacity ABTS˙⁺[2,2-azino-bis (3-ethylbenzothiazoline-6- sulfonic acid)], [DPPH˙(2,2-diphenyl-1-picrylhydrazyl), radical scavenging activity, and ferric-reducing antioxidant power (FRAP)], fatty acids, amino acids, mineral and elemental contents in seaweed Sargassum vulgare, were investigated. Experimental design and animal treatment One hundred and twenty adult males (13 weeks old), Wistar albino male rats (n=15X8) weighing about 180-200 g were brought from Research Institute of Ophthalmology (animal house), Egypt, housed in cages (stainless steel) with good ventilated shields, the rats were acclimated with standard experiment conditions (26±2°C, 12/12 h light/dark, and 65% RH) for one week before the start of the experiment. During the whole experiment, all the animals were fed on well-balanced diet (3.5% fats, 22% proteins, 0.55 table salt, 0.72% molasses, 0.25% vitamins, 60% corn maize, 5% wheat bran, 20% soybeans, and 10% growth additives) and free access to drinking water add libitum for six weeks. Rats were randomly split into eight groups: The rats were randomly divided into eight groups (15 rats each). group I served as normal control rats that were received normal food and water for six consecutive weeks daily. group II Rats subjected to a single dose (6 Gy) of whole body gamma irradiation after one week of the experiment. group III Rats were treated intraperitoneally with seaweed Sargassum vulgare nano methanolic extract at a concentration of 4 g/kg body weight. group IV Rats subjected to a single dose of γ-irradiation (6 Gy) after one week of the experiment, then injected intraperitoneally with seaweed Sargassum vulgare nano methanolic extract at a concentration of 4 g/kg b.wt. twice/week for six consecutive weeks. group V Rats subjected to a single dose of γ-irradiation (6 Gy) after one week of the experiment, then injected intraperitoneally with seaweed Sargassum vulgare methanolic extract with nano ZnO twice/week for six consecutive weeks. group VI Rats subjected to a single dose of γ-irradiation (6 Gy) after one week of the experiment, then injected intraperitoneally with seaweed Sargassum vulgare methanolic extract with nano Fe2O3 twice/week for six consecutive weeks. group VII Rats subjected to a single dose of γ-irradiation (6 Gy) after one week of the experiment, then injected intraperitoneally with seaweed Sargassum vulgare methanolic extract with nano CuO twice/week for six consecutive weeks. group VIII Rats subjected to a single dose of γ-irradiation (6 Gy) after one week of the experiment, then injected intraperitoneally with seaweed Sargassum vulgare methanolic extract with nano [Cu(OAC)2 (HL)2]complex twice/week for six consecutive weeks. Blood and tissue preparation samples Six weeks after the experiment was completed, rats were lightly anesthetized and blood was collected from the internal jugular vein in special tubes. Separated clear sera were kept at -20°C for further biochemical analysis. Then, under deep anaesthesia all rats were sacrificed. Immediately, carefully remove the liver from each rat for all eight groups for histopathological examination. The parameters studied in the current work were inflammatory biomarkers [tumor necrosis factor-α (TNF-α), total heat shock protein (HSP70), interleukin-6 (IL-6), interleukin-10 (IL-10), caspase-3 (CASP-3), monocytes chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), and 8-hydroxy-deoxyguanosine (8-OHDG)], contents of nitric oxide (NO), deoxyribonucleic acid (DNA), malondialdehyde (MDA), antioxidant enzymes (glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), enzyme activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alpha feto protein (AFP), and gamma-glutamyl transferase (GGT), total bilirubin, albumin, total protein, globulin, cholesterol, triglyceride, hematological parameters (haemoglobin (HB), red blood cells (RBCs), white blood cells (WBCs), platelet), kidney functions (creatinine, urea, potassium and sodium), hormonal level of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone in different rat groups were determined. The results of the present study were summarized as follows: 1- Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano [Cu(OAC)2 (HL)2]complex (GVIII) was the most effective treatment in reducing levels of ALT, AST, and AFP as compared to the other groups. Meanwhile, Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano CuO was the most effective treatment in reducing levels of total bilirubin and AFP (GVII). Also, they increased the level of total protein, albumin, and globulin as compared to the gamma irradiation groups. This is attributed to the increased synergistic activity of the powerful antioxidant polyphenolic compounds (radical scavenging properties) as well as other additional secondary metabolites. 2- The gamma irradiation treatment (6 Gy) increased the concentrations of creatinine, urea, and potassium as compared to the control group. In contrast, gamma irradiation (6 Gy) significantly decreased sodium levels when compared to all treatment. However, Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano CuO (GVII) was the most effective treatment in reducing levels of creatinine, Urea, and potassium as compared to the γ-irradiated group. Also, they increased the level of sodium as compared to the γ-irradiated group. This is attributed to the increased synergistic activity of the powerful antioxidant polyphenolic compounds (radical scavenging properties) as well as other additional secondary metabolites 3- Gamma irradiation treatment (6 Gy) increased cholesterol, and triglycerides as compared to the control group. Meanwhile, application of γirradiation (6 Gy)+Sargassum vulgare with nano CuO (GVII) was the most effective treatment in decreasing cholesterol, and triglycerides levels as compared to γ-irradiated group. 4- The gamma irradiation treatment (6 Gy) decreased the concentrations of SOD, GSH, and CAT as compared to the control group. In contrast, gamma irradiation (6 Gy) significantly increased MDA and NO levels when compared to all treatment. However, Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano CuO (GVII) was the most effective treatment in increasing the levels of SOD, GSH, and CAT as compared to the γ-irradiated group. Also, they decreased the level of MDA and NO as compared to the γ-irradiated group. 5- Gamma irradiation treatments increased significantly all the inflammatory biomarkers as compared to the control group and Sargassum vulgare group. However, Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano CuO (GVII) was the most effective treatment in decreasing significantly TNF-α, HsP70, CASP-3, MMP-9, IL-6, IL-10, and MPC-1, as compared to the gamma irradiated group. 6- Gamma irradiation treatment (6 Gy) decreased HB, RBCs, WBCs, and platelets as compared to the control group. The results indicate that the seaweed Sargassum vulgare is nontoxic to the hematopoietic system. In the present study, we assessed the application of S. vulgare methanolic extract (4 g/kg b.wt.) loaded on nano metal particles (ZnO, Fe2O3, [Cu(OAC)2 (HL)2]complex and CuO) ability to mitigate radiation-induced hematological disorders in rats. Rats subjected to γ-irradiation (6 Gy)+Sargassum vulgare with nano CuO (GVII) was the most effective treatment in increasing the HB, WBCs, and platelets as compared to the gamma irradiation treatment. 7- There are many degenerative effects in the liver tissues in gamma irradiated group (6 Gy). Histopathological examination showed to some extent normal structures of the liver in both normal control rats, group of methanolic extract of sargassum only, and gamma irradiated group (6 Gy) treated with S. vulgare methanolic extract (4 g/kg b.wt.) loaded on nano metal particles (ZnO, Fe2O3, [Cu(OAC)2 (HL)2]complex and CuO), and decreased significantly most of the liver tissue injury. CONCLUSION The results obtained from the research study concluded that Sargassum vulgare can be used as a promising functional food ingredient to protect patients and workers during radiation therapy and as a natural therapeutic drug due to its valuable nutritional benefits, safe nature, low cost and also the availability and availability of the moss. Deficiency of dietary supplementation in patients can be overcome with Sargassum vulgare, which may have significant health-promoting potential (potential protective agent) against gamma irradiation-induced toxicity in rats. Associated with the synergistic activity of potent antioxidants, such as polyphenols (free radical scavenging properties), B-complex vitamins, fiber, and essential elements like Fe, Mn, Co, Se, Cu, and Zn which are known to be very important for various metabolic processes in the human body as they are known to be closely linked to growth and health of human being, carbohydrates, fatty and amino acids, proanthocyanidins, saponins, β-carotene, and protein which are important for a good healthy diet to alleviate and ameliorate different apoptotic and inflammatory oxidative stress patterns associated with exposure to gamma radiation. The great health-promoting potential of the macroalga S. vulgare against gamma radiation associated toxicity seems to be due to the synergistic activity of its potent antioxidant phenolics (mainly gallic, ferulic, salicylic, and chlorogenic and p-coumaric acids) and flavonoids (rutin, kaempferol, and hesperidin), as well as other additional polar compounds. These natural antioxidant compounds are distinctly capable of scavenging ROS and subsequently improving the cellular oxidant/antioxidant balance, modulating the immune defense systems, and eventually regulating the signaling pathways that lead to initiation of the proinflammatory cytokines and apoptotic proteins. The preliminary phytochemical analysis for Sargassum vulgare revealed the presence of many active constituents that may be pharmacologically beneficial. The animals were found to be free of any major toxic signs during as well as at the end of the acute and subchronic toxicity study. There were no abnormal signs of any motor or sensory functions. Natural antioxidant compounds present in Sargassum vulgare are clearly capable of scavenging ROS and thereafter strongly improving the cellular balance (oxidant/antioxidant process), preserving normal liver functions, decreasing lipoperoxiation of cells, improving the immune defence systems, increasing antioxidant enzyme activities, and finally downregulating the singalling pathways responsible for the initiation of apoptotic proteins and proinflammatory cytokines. The application of the methanolic extract of Sargassum vulgare with nano-copper oxide, ferric oxide, zinc oxide and copper(II) acetate complex in the presence of the group treated with gamma rays (6 Gy) led to a significant decrease in most liver tissue injuries, which was somewhat similar to the control group. |