Gamma-irradiated Rats Research Articles

Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011

The search for an effective and non-toxic radioprotector is ongoing. We tested a novel, natural aminothiol-based radioprotector, GL2011, that was applied 30 min, 3 h or 6 h after the exposure of male albino Wistar rats to a 6.7 Gy mild dose of gamma radiation. The molecular signatures of radioprotection were investigated with Raman microspectroscopy of brainstem tissue samples. Morphological changes and activation of astrocytes and microglia were assessed by immunohistochemistry. Global markers of neuroinflammation were followed by ELISA to monitor blood plasma levels of proinflammatory (IL-6 and TNF-?) and anti-inflammatory (IL-10) cytokines. A thirty-day follow-up determined survival of unprotected animals 37.5%. A survival increase was observed after radioprotection (75%, irrespective of the time of application). Raman spectra revealed a slightly deleterious effect of radiation on nucleic acids in surviving animals that was mitigated with the radioprotector, as GL2011 preserved the morphology of both astrocytes and microglia, with reduced microglial infiltration. Cytokine assessment revealed an immunomodulatory effect of the novel radioprotector. The overall results point out the positive effects of a single dose of GL2011 applied at different times. The molecular and cellular changes in the brainstem indicate that the radioprotector applied after radiation conferred better protection, which underlines its translation to cure radiation accidents.

Biochemical study on the protective effect of curcumin on acetaminophen and gamma-irradiation induced hepatic toxicity in rats.

Acetaminophen (APAP) is one of the few recommended analgesic and antipyretic drugs in some critical cases such as viral disease COVID-19. However, the unrestricted use of APAP develops liver disorders. Hepatotoxicity and liver injury can also be induced by ionizing radiation (IR) during radiotherapy. The data of the current study represents that treatment of rats with either APAP-overdose, or gamma-irradiation (R) induces hepatotoxicity, results in significant increases of the hepatic-enzymes activities (ALT, AST, ALP, GGT, LDH, and MDH), as well as enhancement of triglycerides, total cholesterol levels, combined with declines in albumin and total protein contents. An enhancement of the lipid peroxides (malondialdehyde; MDA), and nitric oxide levels along with a decline of reduced glutathione contents and suppression of superoxide dismutase, catalase, and glutathione peroxidase activities are also observed within the liver tissues of intoxicated animals. TNF-α, IL-1β, IL-6, iNOS, Cytochrome P450 2E1 (CYP2E1), miR-802 gene expression, NF-κB, and calcium levels are up-regulated, while Nuclear factor erythroid-related factor-2 (Nrf2), Hemoxygenase-1 (HO-1) protein and gene expressions, as well as, glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H-Quinone oxidoreductase (NQO1), and miR-122 gene expressions are down-regulated in the livers of intoxicated animals. All these parameters show significant improvement in R/APAP intoxicated animals. Curcumin pretreatment develops an amelioration of these effects in APAP-overdose, R-exposure, or R/APAP treatments. In conclusion, oral administration of curcumin shows hepatoprotective effects against APAP-overdose induced hepatic damage in normal and gamma-irradiated rats through prospective regulation of the therapeutic targets CYP2E1, Nrf2, and NF-κB, via organizing the miR-122 and miR-802 gene expression.

Cinnamic acid nanoparticles modulate redox signal and inflammatory response in gamma irradiated rats suffering from acute pancreatitis

Acute Pancreatitis (AP) is a multifactorial disease. It was characterized by severe inflammation and acinar cell destruction. Thus, the present study was initiated to evaluate the role the of Cinnamic acid nanoparticles (CA-NPs) as a modulator for the redox signaling pathway involved in the development of pancreatitis. AP in rats was induced by L-arginine and exposure to gamma radiation. The pancreatic injury was evaluated using biochemical and histological parameters. Upon the oral administration of CA-NPs, both the severity of acute pancreatitis and the serum levels of amylase and lipase were decreased. Furthermore, the malondialdehyde (MDA) levels of the pancreatic tissue were significantly reduced and the depletion of glutathione was considerably restored. The injury and apoptosis of pancreatic tissues were markedly improved by the reduction of the caspase-3 levels. Additionally, the alleviation of pancreatic oxidative damage by CA-NPs was accompanied by a down-regulation of the NLRP3, NF-κB, and ASK1/MAPK signaling pathways. Collectively, the current findings showed that CA-NPs could protect the pancreatic acinar cell from injury not only by its antioxidant, anti-inflammatory effect but also by modulation of the redox-sensitive signal transduction pathways contributed to acute pancreatitis severity. Accordingly, cinnamic acid nanoparticles have therapeutic potential for the management of acute pancreatitis.

Protective Role of Juniperus phoenicea L. Leaves Extract against Gamma-irradiation-induced Oxidative Stress.

Radiation exposure can cause several harmful effects in biological systems due to free radical production. Several antioxidants have been tested as potential hepatoprotective agents against ionizing radiation as they lower oxidative stress in normal cells induced by Reactive Oxygen Species (ROS). The present study was conducted to evaluate the possible ameliorative effects of Juniperus phoenicea L. Aqueous leaves extract on different biochemical and histopathological parameters against whole body gamma-irradiation-induced oxidative stress, organ dysfunction and metabolic disturbances in experimental Swiss Albino rats. After a single dose of gamma-radiation (6 Gy), there was a significant reduction in albumin, total protein and globulin levels and a significant increase in the liver enzymes (ALT, AST, ALP and GGT) and lipid profile parameters (cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) in gamma-irradiated rats unlike in normal controls. The gamma-irradiated rats pre-treated with J. phoenicea leaf extracts, however, showed a significant increase in albumin, total protein and globulin levels and a significant reduction in liver enzymes and lipid profile parameters as opposed to the untreated ones. The gamma-irradiated rats showed toxic changes in the liver, whereas, the rats pre-treated with J. phoenicea leaves extract demonstrated a protective effect. Additionally, gamma- irradiation caused myocardial degenerative changes, interstitial edema between muscle fibers, necrosis and inflammatory cells infiltration and fibrotic and cellular damages to the heart, but J. phoenicea leaves extract were found to ameliorate the gamma-irradiation-induced changes in the heart. The results suggested that treatment with J. phoenicea leaves extract is possibly safe and can ameliorate gamma-irradiation-induced oxidative damage and tissue injury in rats. The leaves of J. phoenicea could serve as a potential source of therapeutic antioxidants.

Role of Spirulina on gamma-irradiated rats using Fourier transform infrared attenuated total reflectance and Electron spin resonance for brain

The role of spirulina against brain tissue injury induced by 4 Gy whole body γ-irradiation was studied. Thirty male albino whistler rats were divided into five groups: control (C), spirulina (Sp) 400 mg/kg orally administrated for 2 weeks, irradiated (4 Gy), (Sp+4 Gy), and (4 Gy+Sp). About 24 h posttreatment, fresh brain white matter was extracted from the animal and directly measured by Fourier transform infrared attenuated total reflectance. The detailed spectral analysis were performed in three distinct regions, namely, amide A and lipid structure 3800–2800 cm −1 , protein structure 1800–1300 cm −1 , and helical structure 1400–1000 cm −1 . Sp exerted no significant characteristic changes in both wavenumber and absorbance compared with control. 4 Gy exerted a significant decrease in the absorbance of amide A and significant increase in the saturated lipids, protein, and helical structure regions. Significant changes in the wavenumber (cm −1 ) were found in the 4 Gy for all characteristic functional groups. Deconvolution of secondary structure of amide I showed that 4 Gy exerted significant increase in β-sheet. Electron spin resonance of lyophilized brain tissue indicated increase in the free radicals for 4 Gy. In conclusion spirulina given before or after γ-irradiation ameliorate the changes in brain tissue.

Intestinal injury can be effectively prevented by Dunaliella salina in gamma irradiated rats

Dunaliella salina (D. salina) is one of the most common microalgae that is used as human food. It is isolated from the salty lakes in El-Fayoum and Lake of Bardawil-Sinai in Egypt and can withstand very high concentrations of salt: The potentiality of D. salina, a unicellular biflagellate green alga to protect against intestinal injury induced after radiation exposure was studied. D. salina was given orally in doses of 100 and 200 mg/kg to male Wistar rats for 5 days before exposure to 6 Gray (Gy) gamma radiation and continued for a further two days. Rats were sacrificed 24 h later and intestinal segments were dissected out. One segment was examined histologically and another was used to prepare homogenates to assess relevant biochemical parameters reflecting intestinal injury. Radiation exposure led to a rise in the histological damage score, an increase in tissue tumor necrosis factor (TNF-α), interleukin (IL-1β) and thiobarbituric acid reactive substances (TBARS) but a reduction in tissue reduced glutathione (GSH) and in serum citrulline. Pretreatment with either dose of D. salina effectively reduced the severity of intestinal mucositis induced by gamma radiation.

Effect of Silver Nanoparticles on distribution of Certain Trace Elements in Various Organs of Normal and Gamma Irradiated Rats

Effect of Silver Nanoparticles on distribution of Certain Trace Elements in Various Organs of Normal and Gamma Irradiated Rats

Studying the Ameliorative Effect of Bee Venom Against Damage and Inflammation Induced in Gamma-Irradiated Rats

The aim of this study was focused on investigating the possible protective effect of Bee Venom (BV) against gamma radiation induced damage and inflammation in male rats. Gamma-irradiation (6 Gy) resulted in a significant elevation in the level of tumor necrotic factor-alpha (TNF-α) , interleukin-6 (IL-6) , creatinine kinase-MB (CK-MB) and cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), serum aspartate transaminase (AST) and alanine transaminase (ALT) , serum glucose, malondialdehyde (MDA) concentration and xanthine oxidase activity associated with remarkable decrease in insulin level, glutathione content (GSH) and the activity of xanthine dehydrogenase (XDH), superoxide dismutase (SOD) and catalase (CAT) in heart and liver tissues compared to control group. Injection of BV (5ml/kg b. wt. / day/6weeks) to γ-irradiated rats was found to offer protection against γ-irradiation induced oxidative stress and significantly ameliorated the changes occurred in the above investigated biochemical parameters. It could be concluded that Bee venom clarified a modulatory role against gamma radiation induced oxidative damage and inflammation in the heart and liver tissues.

The effect of salivary gland-derived stem cell transplantation on the regeneration of gamma-irradiated rat submandibular salivary glands: an immunohistochemical study

Background Hyposalivation could be a sequela of radiation impairment in patients with head and neck cancer. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. The aim of this work is to assess the regenerative potential of salivary gland-derived stem cells transplantation in gamma-irradiated rat submandibular salivary glands (SMSGs). Materials and methods Forty-six adult male albino rats were used in this study. Both SMSGs were harvested from five healthy donor rats and used as a source of stem cells. Cells were cultured for 3 and 10 days. Characterization and assessment of stemness after isolation by flow cytometry was carried out using CD24 stem cell marker by fluorescent analysis cell sorting. The rats were grouped as follows: group I (normal untreated control), group II (irradiation group), and group III (irradiation and transplantation group). They were subjected to whole-body gamma radiation with a single dose of 6 Gy. Results Stem cells were successfully isolated from rat SMSGs with positively expressing CD24 and C-kit markers. The statistical analysis revealed significant increase in cell proliferation (proliferating cell nuclear antigen) in both groups II and III compared with the control group I (P˂0.05). Regarding caspase 3 results, the statistical analysis revealed highly significant increase in the mean values of groups II and subgroups III compared with the control group I (P˂0.05). Concerning C-kit expression, group III showed the highest statistically significant mean C-kit expression, followed by group II and group I (P˃0.05). At 2 weeks after transplantation, group II showed the highest statistically significant mean C-kit expression followed by III and control group I (P˃0.05). Conclusion Transplantation of these C-kit+ submandibular salivary gland stem cell (SMSGSCs) could result in amelioration of the severely reduced quality of life of surviving patients with cancer.

Histological and histochemical changes in the liver of gamma-irradiated rats and the possible protective role of Aphanizomenon flos-aquae (AFA)

Histological and histochemical changes in the liver of gamma-irradiated rats and the possible protective role of Aphanizomenon flos-aquae (AFA)

Effects of Vitamin/Sorbent Complexes on Behavioral Activity of Gamma-Irradiated Rats in the Open Field

The dynamics of behavioral indices of male albino rats were examined in the open field test. Total gamma irradiation (absorbed dose 5 Gy) resulted in decreases in the indices of all types of motor and orientational/research activity and increased emotional tension. The treatment of animals with the chitin/protein and carotene-tocopherol complexes (0.35 and .6.67 g/kg, respectively) before and after irradiation, due to the antioxidant and enterosorbent properties of these complexes, significantly moderated the negative effects of irradiation and provided a clear trend toward normalization of the measured behavioral indices (period of observation 30 days).

EFFICIENCY OF FISH OIL IN PROTECTION OF PERIODONTAL LIGAMENT AND MANDIBULAR BONE OF RATS TREATED WITH CISPLATIN AND GAMMA RADIATION

Head and neck cancer is commonly treated with surgery, chemotherapy, radiotherapy either alone or in combination. The purpose of this study is to evaluate the efficiency of fish oil (FO) to preserve periodontal ligament and mandible in gamma irradiated albino rats treated with cisplatin (CP). Thirty male Albino rats were randomly divided into five groups; group C; served as control, group CP; rats were given a single dose of CP (10 mg/ kg body weight i.p), group R; rats were exposed to a single dose of 0.7 Gy γ-rays, group CP + R; rats were given CP and after 24 hours exposed to γ-rays, and group FO+ CP + R; similar to the previous group except for administration of FO (2 ml/ kg body weight) orally and daily for 12 consecutive days before CP injection. The mandibles were collected one day post irradiation and stained with hematoxylin and eosin for histological and histomorphometric analysis. CP and radiation alone or in combination induced bone resorption, degeneration of periodontal ligament fibers. Histomorphometric analysis revealed significant decrease of osteocyte number, fibroblastic and collagen area % and increase of periodontal ligament width. FO protected group showed normal histological appearance of both periodontal ligament and bone. In addition, histomorphometric data revealed normal values of all studied parameters. CP and/ or gamma radiation damage alveolar process and periodontal ligament probably due to osteocyte apoptosis, and supplementary treatment with FO may be potentially useful in protecting alveolar process and periodontal ligament during combined CP chemotherapy and radiotherapy.

Role of Annona muricata (L.) in oxidative stress and metabolic variations in diabetic and gamma-irradiated rats

A. muricata L., commonly known as graviola, is a plant widely distributed throughout the world rich in phytochemicals and minerals. The objective of this study was to investigate the influence of A.muricata on oxidative stress in the liver, kidney and pancreas along with variations in glucose, insulin, lipid profile, liver and kidney functions in diabetic (DM) and γ-irradiated rats (IRR). Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/Kg body weight). Irradiation was performed as whole body γ-irradiation (5 Gy) administered in a single acute dose. A.muricata leaves aqueous extract (100 mg/Kg body weight) was administered via gavages during 2 weeks to diabetic rats or during 2 weeks before γ-irradiation. Diabetic rats received A. muricata during 2 weeks before irradiation. Animals were sacrificed 24 hours post irradiation and/or A. muricata trearment. A. muricata treatment has significantly attenuated hyperglycemia, hypoinsulinemia and dyslipidemia, and reduced the increase of serum alanine and aspartate amino transferase activities and serum urea and creatinine levels. The amelioration in metabolic variations was associated to significant improvement of oxidative stress in tissues notified by a higher superoxide dismutase (SOD) activity and glutathione (GSH) content and a lower malondialdehyde (MDA) content. It could be suggested that the synergistic relationship between the different elements found in the leaf of A.muricata could be beneficial in ameliorating liver and kidney function and correcting metabolic variations associated with oxidative stress in the liver, kidney and pancreas.

Curative role of pantothenic acid in brain damage of gamma irradiated rats.

Radiation induced brain damage is associated with impairment of mitochondrial functions, variations in the level of neurotransmitters, and oxidative stress. Mitochondrial function is closely linked to the level of neurotransmitters since the precursors are supplied by the Kreb's cycle intermediates. The objective of this study was to evaluate the influence of pantothenic acid, an essential component in the synthesis of Coenzyme A (CoA), on the activity of the Krebs cycle enzymes, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), and succinate dehydrogenase (SDH); the level of aspartic, glutamic and GABA; the activity of transaminases, and oxidative stress, in the cerebrum of γ-irradiated rats. Pantothenic acid (26mg/Kg) was orally administered to the rats, 2h after irradiation and during the following 5days. Animals were sacrificed the 7th day post-irradiation. The exposure of male albino rats to γ-rays (5Gy) has triggered oxidative stress notified by a significant elevation in the level of malondialdehyde (MDA), an end product of lipid peroxidation, associated to a significant decrease in the content of phospholipids, and the antioxidant compound glutathione (GSH). The activity of IDH, α-KGDH, and SDH, has significantly decreased, while the level of aspartic, glutamic and GABA has significantly increased. In parallel to these changes, the activity of alanine and aspartate transaminase has significantly increased, compared to their values in the control rats. Pantothenic acid treatment, has significantly attenuated oxidative stress; enhanced the activity of IDH, α-KGDH, and SDH; minimized the increase in the level of amino acids and the activity of transaminases, compared to their values in the cerebrum of irradiated rats. In conclusion, pantothenic acid could improve the level of neurotransmitters amino acids, which depends on the enzymatic activities of Krebs cycle and linked to oxidative stress.

Response of COX2/PGE2 Inflammatory Pathway to Brown Seaweed Extract in Rats Exposed to Gamma Radiation

Background: Systemic inflammation due to radiation exposure has been identified in a biological system by certain metabolic and behavioral disorders. These anarchies mostly mediated under a regulation of cyclooxygenase 2 (COX2) induced production of an inflammatory mediator prostaglandin E2 (PGE2). Aim: This study was undertaken to investigate the anti-inflammatory impact of brown sea weed extract (BSWE) against induction of COX2/PGE2 inflammatory pathway in gamma-irradiated rats. Rats were orally administrated with BSWE (27 mg/kg body weight/day) for 7 consecutive days before exposure to 8 Gy fractionated gamma radiation (2 Gy × 4; every 3 days). Treatment with BSWE was extended along with and in-between irradiation doses for another 14 successive days. Our data demonstrated that the administration of BSWE to rats exposed to gamma radiation, following the regimen suggested, significantly neutralize the changes induced in the inflammatory molecules COX2, PGE2, tumor necrosis alpha (TNF-α), and nitric oxide (NO). In addition, it adjusted significantly the cellular redox tone via regulation of changes induced in malondialdehyde (MDA) reduced glutathione (GSH), superoxide dismutase (SOD) catalase (CAT) and xanthine oxidoreductase system (XOR). Credibly, from the results emerged in this study, it could be suggested that BSWE has substantial anti-inflammatory activities and gamma radiation protection capabilities. It is recommended to include BSWE in the treatment strategy of various inflammatory diseases especially cancer as a safe natural anti-inflammatory agent.

Anti-inflammatory and Anti-nociceptive Effects of piperine in Gamma-irradiated Rats

PIPERINE is an alkaloid that is found naturally in plants belonging to the piperaceae family and has been reported to possess anti-inflammatory properties. The present study was constructed to investigate the possible anti-inflammatory and analgesic effects of piperine on different inflammatory models induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw oedema and hyperalgesia model. Leukocytes count, tumour necrosis factor-α (TNF-α), prostaglandin E

The Protective Effect of Olive Leaves Extract or Bone Marrow Mesenchymal Stem Cells on Skin Tissue Damage Induced in Gamma Irradiated Rats

Aim of the work: this study aimed to examine the histological and histochemical changes in the skin tissue of male rats after exposure to gamma radiation and the possible therapeutic effect of either olive leaf extract or bone marrow mesenchymal stem cells. Material and methods: the present study was applied on forty adult male albino rats (Sprague Dawely strain). The rats were categorized equally into five groups (1-C group: control rats; 2- O group: rats treated with plant leaves extract (15 mg/kg b. wt. /daily); 3-R group: rats exposed to a single dose of gamma-radiation (3 Gy); 4-RO group: rats of this group treated with olive leaf extract 15 mg /kg b.wt./daily one week prior to irradiation and one week post irradiation; 5- RS group: rats of this group were irradiated with 3Gy then treated with bone marrow mesenchymal stem cells (3×106 cells / ml suspension) through the caudal vein about 5 hours post radiation exposure. Histopathological and some common histochemical changes were studied. Results: rats exposed to gamma radiation showed several histological and histochemical changes, these changes were improved by using either olive extract or bone marrow mesenchymal stem cells. The bone marrow mesenchymal stem cells (BMSCs) showed more obvious curative effect than olive leaf extract. Conclusion: the present work showed that both olive leaf extract and bone marrow mesenchymal stem cells have skin tissue radiotherapeutic effects against gamma radiation in male albino rats.

Radio-protective effect of some new curcumin analogues

In the present study, novel symmetrical curcumin analogues (2–7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2–7) were elucidated by elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2–7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2–7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

Modulation of gamma-irradiation and carbon tetrachloride induced oxidative stress in the brain of female rats by flaxseed oil

The activity of flaxseed oil (FSO) on gamma-irradiation (7Gy) and/or carbon tetrachloride (CCl4) induced acute neurotoxicity in rats' brain was investigated. The results revealed a significant decrease (p<0.05) in superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px) activities, reduced glutathione (GSH) and manganese (Mn) contents. Further, a significant elevation (p<0.05) in malondialdehyde, nitric oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), transforming growth factor-beta-1 (TGF-β1), iron (Fe), calcium (Ca), copper (Cu) and magnesium (Mg) levels were observed. Furthermore, the relative ratio of xanthine oxidase (XO) and inducible nitric-oxide synthase (iNOS) gene expression levels were elevated in the brain tissues of γ-irradiated and CCl4 intoxicated animals. Those effects were augmented due to the effect of CCl4-induced toxicity in γ-irradiated rats. The treatment of FSO displayed significant amendment of the studied parameters in the brain tissues of γ-irradiated and CCl4 intoxicated animals. FSO has a neuroprotective effect against CCl4-induced brain injury in gamma-irradiated rats. This effect is interrelated to the ability of FSO to scavenges the free radicals, enhances the antioxidant enzymes activity, increases GSH contents, down-regulates the inflammatory responses, ameliorates the iron, calcium, copper, magnesium, manganese levels and inhibiting the gene expression level of XO and iNOS in the brain tissues of intoxicated animals. In conclusion, this study demonstrated that the potent antioxidant and anti-inflammatory activities of FSO have the ability to improve the antioxidant status, suppress the inflammatory responses, and regulate the trace elements in the brain tissues of γ-irradiated, CCl4, and their combined effect in intoxicated animals. Consequently, FSO exhibited neuroprotective activity on γ-irradiated, CCl4, and their combined effect induced brain injury in rats.

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4⁺ and CD8⁺ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.