Radiolysis induced by gamma radiation generates a lot of ROS which eventually severely damage living cells and cause organ dysfunction due to an imbalance between oxidants and antioxidants1,32.
The phenomenon of oxidative stress is a consequence of the imbalance between the increased production and accumulation of ROS in tissues and the failure of the biological system to detoxify these reactive products that leads to high damage and destruction of living tissues9. In recent years, many antioxidants have been used for their supposed or actually beneficial effect against oxidative stress, such as polyphenols, saponins, and vitamin E 33.
Recently, scientists interest in searching for natural compounds as antioxidants from plant substances has increased due to ease of use, safe nature and low cost to avoid the use of artificial compounds that many poisonous facet effects and because of its very excessive costs 2,8.
In the Nubian Desert in southern Egypt, and northern Sudan a rare type of fan palm (Medemia argun) is found10,11,34, and has ecological importance as it provides shelter and food for desert wildlife. In ancient Egypt, the fruits of these palms were of great nutritional value, as evidenced by their presence in offerings in tombs11,12.
It appears that the many significant medicinal benefits of MA extract to reduce the adverse effects that occur in rats as a result of gamma-radiation exposure may be attributable to the solidarity activity of the strong antioxidant polyphenols (phenolic and flavonoid) as well as other additional bioactive secondary metabolites, which are clearly capable of scavenging free radicals and thus highly improving cellular redox/antioxidant balance, increasing immune defense systems, and ultimately downregulating the signaling pathways that trigger the initiation of proinflammatory mediator cytokines and health-damaging programmed proteins7,8,9.
The median lethal dose (LD50) for Medemia argun ethanolic seed’s extract (200 mg/Kg b.wt.) was similar to that obtained by 35.
In this study, polar solvents, such as ethanol, were used because it is high efficient than other non-polar solvents and water in extracting antioxidants compounds from MA. Twenty-two fractions of polyphenols (phenolic and flavonoid). Medemia argun contains a range of other bioactive secondary metabolites with important, beneficial and antioxidant properties such as, saponins, protein, proanthocyanidin (condensed tannins), and carbohydrate, which are similar to that of 7,8,9.
Medemia argun rich with proanthocyanidins that contains subunits (catechin, afzelechin, and gallocatechin). The high therapeutic value of MA may be related to occurrence of high concentrations of many polyphenol fractions, which are an integral part of the human diet and have important and beneficial effects on human health and disease resistance 9,13,15.
Proanthocyanidins have important and promising antioxidant characteristics and may protect and preserve biomolecules (proteins, DNA, and lipids) exposed to free nitrogen ions, including peroxynitrite (ONOOˉ) and free oxygen radicals. Also, as a significant and important protective factor against oxidative/nitrifying stress associated with many harmful and different diseases, neurodegeneration, cardiovascular and cancer15.
Antioxidant polyphenols (radical scavenging properties) in MA, which is characterized as being natural and has many health benefits, which can be recommended for use in food industry (as important and useful nutritional supplements) instead of artificial antioxidants that have many severe and harmful effects on human health7,8,9 .
In the desert environment in Egypt, MA fruits are used and an important source of good nutrition because it contains many important nutrients such as polyphenolic compounds (radical scavenging properties), B-complex vitamins, fibers, amino acids, essential minerals (K, Na, Ca, and Mg), carbohydrates, glucose, and fatty acids (Mohammed et al., 2019). In the Nubian desert in Egypt, the fruits are used as a source of food for humans and mammals, where the fruits are scarce 9.
The results of the research showed that exposure to gamma radiation increased significantly DNA damage exemplify by the tail moment in the liver tissues. The DNA damage identified in cytogenetic analysis and Comet assay can be produced from increased free oxygen radicals and thus a significant increase in harmful oxidative stress activity as an actual result of radioactive exposure 1,2,36. Free oxygen radicals increased DNA damage and prevent cell division (unrepaired) or disrupted damage that induced mutations. Starting of apoptosis produce Comet picture, that values and tail parameters are similar to cells with mild DNA damage 37. On the other hand, rats that received an intraperitoneally injection of the ethanolic crude extract of Medemia argun (200 mg/kg b.wt.) significantly decreased the above parameters as compared to γ-radiated rats indicating positive therapeutic impact of M. argun in repairing the fragmented DNA due to exposure to γ-irradiation.
Previous study revealed that γ-radiation induced a significantly increased (p≤0.05) liver functions, ALT, AST, GGT, AFP and ALP 1,36. γ-irradiation increased level of serum transaminases by increasing the oxidation of the liver cell membrane, which leads to destruction and increased permeability of membrane, which eventually causes the transaminases to leak into the blood 38.
Elevated biochemical assays including transaminases (AST, ALT), ALP, and GGT are known indicators of liver function and sensitive markers of confirmed liver injury and subsequent leakage of these enzymes in irradiated rats from the tumor cell into the blood circulation 36.
However, γ-radiation rats that were subsequently given MA (200 mg/kg b.wt.) for six weeks revealed significantly decrease (p≤0.05) in liver functions (ALT, AST, GGT, ALP and AFP), this is attributed to the increased synergistic activity of the powerful antioxidant polyphenolic compounds (radical scavenging properties) as well as other additional secondary metabolites7,8,9.
γ-radiation induced a significantly increase (p≤0.05) in anti-inflammatory biomarkers (TNF-α, IL-6, CASP-3, MPC-1, and MMP-9), 8-OH-Dg and DNA fragmentation2,36. However, γ-irradiation induced a significantly deceased (p≤0.05) in IL-10, total protein and albumin36.
γ-irradiation inhibit the release of the inflammatory mediators (TNF-α, IL-6, CASP-3, MPC-1, and MMP-9) for decreasing inflammatory responses36,39.
Moreover, caspase-3 is a major and important enzyme in the apoptosis cascade and it is very often to reveal the extent of apoptotic activity. MA treatment inhibited caspase-3 levels in rats9.
Decreasing significantly of pro-inflammatory biomarkers, IL-6, TNF-α, and CASP-3 in γ-irradiated rats treated with MA ethanolic seed’s extract is likely related to the potent anti-inflammatory and inhibitory effects of polyphenols in inhibiting nuclear factor-κB transmission and regulating inflammation-related expression of nitric oxide synthase1.
Unfortunately, the present investigation revealed γ-irradiation treatment caused significantly increase (p≤0.05) in concentration of NO, and MDA in parallel with significantly decrease in GSH, SOD, and CAT1,2,39,40,41,42,43. Gamma radiation increased concentration of (NO, and MDA). Radiolysis of water induced by gamma irradiation caused a marked decrease in the levels of antioxidant molecules 44. Increased GGT activity of γ-radiated group may be attributed to the decreased hepatic GSH activity38.
Preventing the high level of nitrogen oxide release during hepatocarcinogenesis of MA-treated animals reflects an improvement in the antioxidant status of the liver9.
Antioxidant enzyme activity (GSH, SOD, and CAT) decreased significantly by γ-radiation which are distinctly capable of scavenging ROS1,39,43,45. Proanthocyanidin increased significantly SOD activity43.
Conversely, MA application at 200 mg/kg b.wt. for γ-irradiation treated rats effectively deceased significantly (p≤0.05) NO, and MDA concentrations29. Also, they significantly increased (p≤0.05) activity of antioxidant enzyme GSH, SOD, CAT, and POD 29.
In the desert environment in Egypt, MA fruits are used and an important source of good nutrition because it contains many important nutrients such as polyphenolic compounds (radical scavenging properties), B-complex vitamins, fibers, amino acids, essential minerals (K, Na, Ca, and Mg), carbohydrates, glucose, and fatty acids, which is important for a good healthy diet to overcome oxidative stress caused by γ-radiation7,8,9. In the Nubian desert in Egypt, the fruits are used as a source of food for humans and mammals, where the fruits are scarce 9.
Hsp70 proteins is a molecular chaperone which increased in response to stress and protect cells from oxidative or thermal stress 46. Hsp70 binds to its protein substrates and stabilize them against aggregation or denaturation until conditions improve. Hsp70 has many responsibilities during normal growth; degradation of unwanted proteins, subcellular transport of proteins, and helps in the folding of newly synthesized proteins 47,48,49. γ-radiation-induced harmful oxidative stress, which increased HsP70 content as a biological response 47.
γ-radiation increased significantly (p≤0.05), m-RNA transcript levels of heat shock protein (HsP70) in liver tissues of rats in comparison with control and rats treated only with MA. However, γ-irradiation treated rats that were subsequently given MA (200 mg/kg b.wt.), showed a significantly decreased (p≤0.05) level of HsP70 expression in liver tissues as compared to γ-irradiation treated rats, but still greater than normal. Our result points the great potential impact of MA extract, due to its high antioxidant polyphenols contents, in decreasing the HsP70 level in γ-irradiated rats.
Malondialdehyde, are important because they can also induce damage DNA50. A highly active hydroxyl radical can break the DNA threads creating 8‑hydroxydeoxyguanosine. Moreover, the 8-OH-dG adduct was identified as a marker of DNA damage51.
Exposure to gamma radiation leads to a significant dysfunction of the organs by oxidizing the lipid bilayer, thus affecting its integrity and greatly increasing its permeability7,39,52,53.
Free radicals generated by γ-radiation alone induced lipid peroxidation, oxidative damage and liver cell apoptosis in rat tissue as proven by significantly increase in liver MDA (cytotoxic aldehydes) content; and significant decrease in total antioxidant activities39.
MA administration to γ-irradiated rats significantly (p≤0.05) decreased the MDA concentration, indicating its powerful antioxidant polyphenols and many secondary metabolites7,8,9. With the help of exogenous antioxidants, tissues can resist damage40. Biochemical results came to agree with the histopathological observations.