Objectives: This study was conducted to determine the efficacy of mesenchymal stem cells (MSCs) or low-dose gamma radiation (LDR) on liver injury compared to the effect of olive leaf extract as a hepatoprotective agent. Methods: Rats were allocated into six groups; group I served as the negative control. Group II received 5% dextran sodium sulfate (DSS) in its drinking water for 1 week. Group III was injected with a single dose of 1 × 10⁶ bone marrow-derived mesenchymal stem cells (BM-MSCs) intravenously. Group IV was treated as in group III after 5% DSS treatment. Group V was given 5% DSS, followed by olive leaf extract (OLE) (1000 mg/ kg, oral). Group VI: 5% DSS for 1 week, then was exposed to low-dose gamma radiation (LDR) (0.05 Gy). Results: Rats treated with OLE, BM-MSCs, or exposed to LDR exerted significant alleviation in all hepatic biomarkers, significant enhancements in oxidative stress parameters, and improvements in inflammatory biomarkers Interleukin-1 beta (IL-1β) and Interferon gamma (INF-γ) hepatic contents compared with those of the DSS group. Histological pictures emphasized the biochemical findings. Conclusions: BM-MSCs might be a valuable therapeutic approach to overcome hepatic injury. Exposure to LDR provided protective mechanisms that allow the body to survive better.

Introduction: This work aims to validate the ameliorative influence of metformin against endoplasmic reticulum stress (ERS)-prompted apoptosis caused by vanadium pentoxide (V₂O₅) or gamma-irradiation (γ-irradiation) in hepatic tissues of male rats. Methods: There were six groups of rats: the control, metformin (100 mg/kg body weight, i.p.), V₂O₅ (12.5 mg/kg body weight, i.p), V₂O₅ plus metformin, γ-irradiation group (acute dose 6 Gy), and γ-irradiation plus metformin; for 2 weeks. Hepatic malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated. Additionally, the protein expression of certain endoplasmic reticulum stress-related (ERS) biomarkers; Inositol requirement enzyme 1α (IRE1α), TNF receptor-associated factor 2 (TRAF2), and Apoptosis signal-regulating kinase 1 (ASK1); were estimated in hepatic tissues. Moreover, apoptosis-associated biomarkers; Bax, Bcl-2, caspase-3 and HSP70 levels have been assessed. Furthermore, histopathological changes in hepatic tissues were observed. Results: Metformin with V₂O₅ or γ-irradiation significantly decreased MDA, IRE1α, TRAF2, ASK1, Bax, and caspase-3 compared with V₂O₅ or γ-irradiated groups. Meanwhile, it significantly elevated GSH, Bcl-2, and HSP70 levels compared to exposure to V₂O₅ or γ-irradiation groups. Interestingly, the obtained results concur well with histological alterations. Discussion: Our findings demonstrate the protective influence of metformin against ER stress-induced apoptosis through enhancing GSH and reduction of ERS and apoptosis suggesting that metformin may have positive impacts as a potential radiation protector beyond its glucose-lowering effect.