Gamma-irradiated Rats Research Articles

Nano-pregabalin effectively mitigates Glut, CGRP and NE neurotransmitters abnormalities in the brain of gamma irradiated rats with reserpine-induced fibromyalgia model: Behavioral and neurochemical studies

AimsFibromyalgia (FM) is an idiopathic syndrome with painful burdensome symptoms. Radiotherapy is one of the main therapeutic modalities for treating various malignancies and there is a probable association between FM exacerbation and exposure to ionizing radiation. Based on that nanomedicines progressively being explored for their promising applications in medicine, the aim of the current study is to assess the possible therapeutic benefits of nanoform of pregabalin (N-PG) in managing FM symptoms during being exposed to ionizing radiation. Main methodsRats were allocated into four groups. First group served as control, the other three groups received gamma radiation (2 Gy/day) after 1 h of reserpine administration (1 ml/kg per day, s.c.) to induce FM for three successive days. On the next day, third and fourth groups received (30 mg/kg, p.o.) of PG and N-PG, respectively once daily for ten consecutive days. Tail flick test was performed and von Frey filaments were used to assess mechanical allodynia/hyperalgesia, and then rats were sacrificed to obtain brains. Key findingsN-PG effectively replenished reserpine effects and treated both allodynia and hyperalgesia, improved thermal allodynia, effectively recovered all neurotransmitters near to normal baseline, inhibited oxidative stress status via decreasing malondialdehyde (MDA), increasing glutathione (GSH) and superoxide dismutase (SOD), it had strong anti-inflammatory effect as verified by reducing both cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kB) in addition to inhibition of intrinsic apoptosis through caspase-3 (casp-3) decrease and B-cell lymphoma-2 (Bcl-2) increase. Histopathological and immunohistochemical results confirmed the biochemical findings. SignificanceN-PG could be a promising drug for treating FM especially when there is urgent need to expose patient to ionizing radiation.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1β and PARP1 pathways

BackgroundFibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. MethodsGamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. ResultsN-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1β and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. ConclusionThis study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

Will Nigella sativa oil protect parotid glands of rats against cranium gamma irradiation? Histological and immunohistochemical evaluation

BackgroundRadiation plays an essential role in treating malignancies. Radiation exposure of salivary glands often results in permanent loss of their functions; therefore, their protection against radiation is crucial. Nigella sativa oil (NSO) is a useful antioxidant against free radicals. The purpose of this study was to investigate the radio-protective effect of NSO on oxidative injury of parotid glands of gamma-irradiated rats. Methods: Twenty-eight male albino rats were divided into four groups (n = 7): Group 1: Neither NSO nor radiation, Group 2: Rats received NSO 400 mg/kg, Group 3: Rats received 15 Gy cranium gamma irradiation & Group 4: Rats received gamma irradiation and NSO. Rats were sacrificed two weeks after the last NSO dose. Histological sections of parotid glands were stained with H&E, Masson’s trichrome and anti-TGF-β antibodies. Area percentage of Masson’s trichrome and TGF-β expression was morphometrically examined. Results: Parotid glands of control and NSO groups revealed normal morphology. Gamma-irradiated glands showed loss of normal acinar architecture and slight acinar shrinkage. NSO treatment of gamma-irradiated glands preserved acinar outline and architecture. Masson’s trichrome stained samples revealed trace amounts of collagen fibers in control and NSO groups, and excessive amounts of collagen fibers in gamma-irradiated group, in addition to few collagen fibers for gamma-irradiated glands treated with NSO. Additionally, control and NSO groups showed negative TGF-β expression. Gamma-irradiated group showed high TGF-β expression, while NSO treated gamma-irradiated group showed moderate TGF-β expression. Conclusions: Gamma-irradiation adversely affected parotid glands, and in contrast, NSO seemed to positively counteract this adverse effect.

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin.

Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis. Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100mg/kg; four times a week for four weeks; group U received rutin at a dose of 50mg/kg; three times a week for three weeks; group RF received a single dose (5Gy) of gamma radiation followed by iron at a dose of 100mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination. In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB. In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.

Estimation of the Role of Different Staining Protocols on Micronucleus Test Accuracy in Gamma-Irradiated Rats

Estimation of the Role of Different Staining Protocols on Micronucleus Test Accuracy in Gamma-Irradiated Rats

Vitamin E ameliorates oral mucositis in gamma-irradiated rats (an in vivo study)

BackgroundRadiation therapy is the primary treatment for neck and head cancer patients; however, it causes the development of oral mucositis accompanied by tissue structure destruction and functional alteration. This study was conducted to evaluate the effect of different doses of vitamin E as a treatment for radiationinduced oral mucositis in rat model.Methods35 male albino rats were randomly divided into five groups: control, untreated radiation mucositis (single dose of 20 Gy), treated radiation mucositis; radiation (single dose of 20 Gy) then vitamin E at doses of 300, 360 and 500 mg/Kg for seven days started 24 h after irradiation. Body weight and food intake were evaluated for each rat. The mucositis score was assessed every day. Rats were sacrificed once at the end of the experiment, and tongue specimens were stained with hematoxylin and eosin, anti P53 and anti Ki67 antibodies.ResultsResults indicated more food intake and less weight reduction in vitamin E treated groups and the contrary for gamma-irradiated group. Additionally, vitamin E delayed the onset and decreased the severity and duration of mucositis. It also restored the histological structure of lingual tongue papillae. Vitamin E treated groups showed a significant higher Ki67 and lower P53 expression as compared to untreated radiation group. The overall improvement increased as vitamin E dose increased. Finally, the amelioration can be attributed to the decreased apoptosis and increased proliferation of cells.ConclusionsVitamin E especially at dose of 500 mg/Kg could be an effective treatment for radiation-induced oral mucositis.

Histomorphometric Analysis of the Healing Capacity of Low-Level Laser on Thermally Induced Tongue Ulcers for Gamma-Irradiated Rats.

Objective: This study aimed to assess the efficacy of low-level laser therapy (LLLT) for treating thermal tongue ulcers in gamma-irradiated rats. Background: Postradiotherapeutic trauma may cause cell death, tissue damage, organ dysfunction, and loss of hematological components. Materials and methods: Thermal ulcers were induced on the dorsal surfaces of tongues of gamma-irradiated rats (15 Gy). Rats were divided into three groups, group 1 received no treatment, group 2 was subjected to a single dose of diode laser 807 nm with energy density 4 J/cm2, and group 3 was subjected to the same dose of LLLT but fractionated into three sessions at days 1, 3, and 5 after ulcers induction. Ulcers were assessed clinically for their areas and healing percentage. Specimens were examined for the quality of ulcer closure and expression of IL-1β and TGF-β1. Results: Results revealed significant improvement of ulcer healing clinically and histologically in both treatment groups compared to control. Moreover, IL-1β and TGF-β1 expression in both treatment groups was high at the earlier stage of healing then declined by time to reach a normal level. However, untreated group showed higher expression of IL-1β and TGF-β1 compared to treatment groups. In addition, IL-1β expression decreased by time but still of high level and TGF-β1 expression increased then declined. Conclusions: We concluded that gamma radiation-impaired mucosal healing could be related to the over expression of IL-1β and TGF-β1. LLLT, whether one session or fractionated, could be an effective treatment for postradiotherapeutic ulcers. The healing power of LLLT might be due to modulation of IL-1β and TGF-β1. Clinical Trial Registration number is 25A122.

Etoricoxib nanostructured lipid carriers attenuate inflammation by modulating Cyclooxygenase-2 signaling and activation of nuclear factor-κB-p65 pathways in radiation-induced acute cardiotoxicity in rats

The current investigation aimed to explore the potential of etoricoxib nanostructured lipid carriers (ET-NLCs) as an anti-inflammatory drug in radiation-exposed rats, with a focus on assessing its efficacy in reducing inflammation while minimizing cardiac toxicity compared to conventional etoricoxib (ET) treatment. The ET-NLCs were prepared by the low-temperature melt emulsification solidification technique. Various techniques were employed to characterize the NLCs. Rats were exposed to gamma-irradiation (6 Gy) to induce cardiac inflammation and injury, followed by oral administration of ET or ET-NLCs (10 mg/kg b.w.) for 14 consecutive days. Results demonstrated a significant increase in the levels of malondialdehyde (MDA), cyclooxygenase-2 (COX-2), nuclear factor kappa-B p65 (NF-κB-p65), and poly ADP-ribose polymerase (PARP-1) in the heart tissues of gamma-irradiated rats compared to the control group. This increase was accompanied by a reduction in the activity of antioxidant enzymes. However, treatment with ET and ET-NLCs exhibited a positive impact on these levels. Interestingly, the efficacy of ET-NLCs in mitigating radiation-induced inflammation in heart tissue was found to be superior to that of ET. In conclusion, the study suggests that the utilization of NLCs as a drug delivery system for ET may not only enhance its therapeutic efficacy but also help reduce the cardiovascular risks associated with ET, specifically focused on individuals who had been exposed to gamma radiation. These findings open new avenues for further research in the development of effective and safer therapeutic strategies for managing inflammatory diseases and their impact on cardiovascular health.

Ubiquinol preserves immune cells in gamma-irradiated rats: Role of autophagy and apoptosis in splenic tissue

Radiation has been applied in cancer treatment to eradicate tumors and displayed great therapeutic benefits for humans. However, it is associated with negative impacts on normal cells, not only cancer cells. Irradiation can trigger cell death through several mechanisms, such as apoptosis, necrosis, and autophagy. This study aimed to investigate the radioprotective efficacy of ubiquinol against radiation-induced splenic tissue injury in animals and the related involved mechanisms. Animals were classified into four groups: group 1 (normal untreated rats) received vehicle 5 % Tween 80; group 2 received 7 Gy γ-radiation; group 3 received 10 mg/Kg oral ubiquinol post-irradiation; and group 4 received 10 mg/Kg oral ubiquinol before and after (pre/post-) irradiation. Ubiquinol restored the spleen histoarchitecture, associated with improved immunohistochemical quantification of B and T lymphocyte markers and ameliorated hematological alterations induced by irradiation. Such effects may be due to an enhanced antioxidant pathway through stimulation of p62, Nrf2, and GSH, associated with reduced Keap1 and MDA. Moreover, ubiquinol decreased mTOR, thus enhanced autophagy markers viz. LC3-II. Furthermore, ubiquinol showed an antiapoptotic effect by enhancing Bcl-2 and reducing caspase-3 and Bax. Consequently, ubiquinol exerts a splenic-protective effect against irradiation via enhancing antioxidant, autophagic, and survival pathways.

Rutin protects against gamma-irradiation and malathion-induced oxidative stress and inflammation through regulation of mir-129-3p, mir-200C-3p, and mir-210 gene expressions in rats’ kidney

Kidney injury represents a global concern, leading to chronic kidney disease. The organophosphate insecticide malathion (MT) demonstrates environmental disturbance and impairment of different mammalian organs, including kidneys. Likewise, gamma-irradiation (IRR) provokes destructive effects in the kidneys. Rutin is a flavonoid glycoside that exhibits nephro-protective and radio-protective properties. This manuscript focused on investigating the protective response of rutin on MT- and IRR-triggered kidney injury in rats. Rats were randomly divided into eight groups of twelve: G1 (C), control; G2 (Rutin), rutin-treated rats; G3 (IRR), gamma-irradiated rats; G4 (MT), malathion-treated rats; G5 (IRR/MT), gamma-irradiated rats treated with malathion; G6 (IRR/Rutin), gamma-irradiated rats treated with rutin; G7 (MT/Rutin), rats treated with malathion and rutin; and G8 (IRR/MT/Rutin), gamma-irradiated rats treated with malathion and rutin, every day for 30 days. The results demonstrated that rutin treatment regulated the biochemical parameters, the oxidative stress, the antioxidant status, and the inflammatory responses due to the down-regulation of the renal NF-κB p65 protein expression. Moreover, it amended the activity of acetylcholinesterase (AchE), angiotensin ACE I, and ACE II-converting enzymes. Besides, it regulated the iNOS, eNOS, miR-129-3p, miR-200c, and miR-210 gene expressions and bradykinin receptor (B1R and B2R) protein expressions. Histopathological examinations of the kidney tissue confirmed these investigated results. It could be concluded that rutin demonstrated nephro/radioprotection and counteracted the toxicological effects triggered in the kidney tissues of IRR, MT, and IRR/MT intoxicated rats, via regulating miR-129-3p, miR-200c-3p, and miR-210-3p gene expressions, which consequently regulated B2R protein expressions, ACE II activity, and HIF-1α production, respectively.

The probable radioprotective role of Acacia nilotica L. against biochemical and cytogenetic disorders induced in gamma irradiated male rats

Gum Arabic (Acacia nilotica L.) is a respected plant that has many nutrients and curative practices. It hinders, improves, or manages many disorders. The radio-protective activity of Acacia nilotica was investigated against γ-rays-induced testicle damage in rats. Twenty-four rats were correspondingly distributed into 4 groups; control, Acacia nilotica (15mg/kg, daily for 30 days), γ-irradiated (5Gy γ-rays, single dose) and Acacia nilotica plus γ-rays treated groups. The plasma testosterone and total antioxidant status (TAS) were estimated. Lipid peroxidation; malondialdehyde (MDA), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), also glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor-α (TNF-α) with interleukin-1β (IL-1β), were determined in the testicle tissues. A testis weight, sperm count and motility, peripheral-blood and bone-marrow micronuclei (PMN and BMN), and frequency of chromosomal aberrations (CAs) were scored. A significant decline in the levels of plasma testosterone with TAS observed in the γ-irradiated rats. The results also showed significantly increased levels of testicle MDA, inflammatory markers, PMN, BMN and CAs frequencies and decrease in testes weight, sperm count and motility and levels of testicle antioxidants markers in gamma irradiated group. All these biochemical and fertility indices results were significantly enhanced in the Acacia nilotica plus γ-rays treated groups. However, the possible alleviate activity of Acacia nilotica on γ-rays-induced testicle injury in rats has not previously conversed, and this is the topic of this study.

Potential Protective Effect of Bromelain and Pineapple Extract on Gamma Irradiated Female Rats: A Study of Oxidative Stress, Apoptosis, and Hormonal Changes

Potential Protective Effect of Bromelain and Pineapple Extract on Gamma Irradiated Female Rats: A Study of Oxidative Stress, Apoptosis, and Hormonal Changes

The Protective Effect of Curcumin on the Proliferation and Colonization of Spermatogonial Stem Cells in Gamma-Irradiated Rats

Background & Objective: One of the side effects of radiotherapy can be damage to spermatogonial stem cells that may lead to spermatogenesis disorders and sterility. Protective effects of curcumin on normal cells against radiotherapy side effects have already been shown. In the current study, the protective effects of curcumin on the spermatogonial stem cells against gamma radiation were evaluated.
 Materials & Methods: This study was done on 50 adult rats in 10 experimental groups. Four groups were injected 0, 25, 50, or 100mg/kg of curcumin in 1ml olive oil for 15 days intraperitoneally, then exposed to radiation at 2 Gy on the next day. Also, four groups were treated like above but without radiation; and two groups as control with and without radiation. The day after radiation, all of the rats were euthanatized, their testes were removed, and they underwent enzymatic digestion to co-culture spermatogonial stem cells. After 12 days, the colonization of spermatogonial stem cells was assessed.
 Results: There was a significant decrease in the colonization of spermatogonial stem cell proliferation in groups that had taken radiation but not curcumin. There was a significant increase in the colonization of spermatogonial stem cells in the group which had taken radiation whit maximum curcumin compared with the other irradiated groups and was similar to non-irradiated control animals. Colonization of spermatogonial stem cells in non-irradiated animals treated with curcumin had increased compared with control groups.
 Conclusion: Injection of curcumin can protect spermatogonial stem cells against radiation. Thus, curcumin may prevent sterility in men who undergo radiotherapy.

Cytogenetic and immunological efficacy of nicotiflorin and rutin combination on gamma irradiated rats

Cytogenetic and immunological efficacy of nicotiflorin and rutin combination on gamma irradiated rats

Effect of Lactobacillus species on apoptosis-related genes BCL2, BAX, and caspase 3 in the testes of gamma-irradiated rats.

Ionizing radiation has various applications, including uses in medicine, industry, agriculture, and research. However, ionizing radiation is accompanied by side effects in normal radiosensitive tissues. Probiotics as natural radioprotective agents can protect normal tissues from ionizing radiation. In this regard, this study aimed to investigate the effect of Lactobacillus species on apoptosis-related genes BCL2, BAX, and caspase 3 (CASP3) in the testes of gamma-irradiated rats. A total of 30 male Wistar rats were involved in this study. The animals received the whole- body radiation with the dose rate of 2 Gy gamma-ray and were orally gavaged with 0.2 mL of 1×1010 Lactobacillus species in phosphate-buffered saline (PBS) for 4 weeks. Then, the relative gene expression levels of BCL2, BAX, and CASP3 in the testis were assessed by using the quantitative real-time polymerase chain reaction (qRT-PCR). Compared with the control group, radiation significantly downregulated the BCL2 and upregulated the BAX and CASP3 genes (p<0.0001). However, Lactobacillus species significantly reversed these effects. All in all, according to our results, employing Lactobacilli probiotics as a natural radioprotector may protect radiosensitive tissue from damage.

The protective role of l-Carintine and vitamin E on gamma irradiated rat’s tongue mucosa

The protective role of l-Carintine and vitamin E on gamma irradiated rat’s tongue mucosa

The protective role of l-Carintine and vitamin E on gamma irradiated rat’s tongue mucosa

The protective role of l-Carintine and vitamin E on gamma irradiated rat’s tongue mucosa

Garcinia kola improves cognitive and motor function of a rat model of acute radiation syndrome in the elevated plus maze.

We reported recently that the elevated plus maze is a good tool for evaluating cognitive and motor functional changes in gamma-irradiated rats as a model for new drug evaluation and monitoring. The capacity of Garcinia kola to mitigate radiation-induced brain injury is currently unknown. We therefore assessed the effects of the neuroprotective medicinal plant Garcinia kola, on the cognitive and motor changes in this murine model of acute radiation syndrome. Wistar rats exposed once to an ionizing dose of Tc99m-generated Gamma radiation were treated with an ethyl acetate fraction of methanolic extract of Garcinia kola seeds (content of 100 mg/kg of extract) for 9 weeks. Cognitive and motor function indicators were assessed in the elevated plus maze in these animals and compared with irradiated control groups (vitamin C- and vehicle-treated groups) and the non-irradiated control rats. The irradiated control group displayed cachexia, shaggy and dirty fur, porphyrin deposits around eyes, decreased exploratory activity, reduced social interactions and a loss of thigmotaxis revealed by a marked decrease in rearing episodes and stretch attend posture episodes close to the walls of elevated plus maze closed arm, an increased central platform time, and decreases in open arm time and entries. This group further displayed a decrease in head dips and grooming episodes. Treatment with Garcinia kola, and in a lesser extent vitamin C, significantly prevented the body weight loss (P < 0.001) and mitigated the development of elevated plus maze signs of cognitive and motor affections observed in the irradiated control group (P < 0.05). Altogether, our data suggest for the first time that Garcinia kola seeds have protective properties against the development of cognitive and motor decline in the acute radiation syndrome-like context. Future studies are warranted to characterize the molecular mechanisms and neuronal networks of this action.

Histological Evaluation of Bioceramic Sealer Effect in Animal Model after Exposure to Gamma Radiation

Purpose: This study was carried out to evaluate the bone tissue reactions to TotalFill Bioceramic (BC) and Zinc oxide eugenol (ZOE) sealers in gamma-irradiated rats. Materials and methods: In this study, round osseous bone defects were produced in the tibia of 48 male Albino rats (weighing120–150g). Group 1: 9 control non-irradiated rats, Group 2: 9 control irradiated rats, and Group 3: 30 irradiated rats in which the surgical cavities were filled with TotalFill sealer in the right tibia and ZOE in the left tibia. The assigned animals were euthanized on 7, 14, and 28 days. For histopathological examination, tissue sections stained with H & E were examined by a light microscope. Results: At 7 days, the inflammatory response of all studied groups (1, 2, and 3) showed no significant differences (p-0.092). The inflammatory response significantly decreased from 14 to 28 days in all groups, virtually disappeared in the non-irradiated group whilst intense inflammatory infiltrate was still observed in 40% of ZOE group samples with a significant difference between TotalFill vs. ZOE sealer (p- < 0.009). Bone tissue at 14 days showed severe resorption in many areas in irradiated animals that reversed at 28 days. In group 3 treated with TotalFill sealer, fiber condensation was observed in surgical cavity at 14 days which was replaced by trabeculae of bone tissue at 28 days while this event was focal in ZOE sealer. Conclusion: TotalFill sealer proved to be more compatible and has some repair potential than ZOE sealer in irradiated animals

The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling

Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.