Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it’s mostly used in chemotherapeutic comb...

The present work investigates the potential role of metformin nanoparticles (MTF-NPs) as a radio-protector against cardiac fibrosis and inflammation induced by gamma radiation via CXCL1/TGF-β pathway. Lethal dose fifty of nano-metformin was determined in mice, then 21 rats (male albino) were equally divided into three groups: normal control (G1), irradiated control (G2), and MTF-NPs + IRR (G3). The possible protective effect of MTF-NPs is illustrated via decreasing cardiac contents of troponin, C-X-C motif Ligand 1 (CXCL1), tumor growth factor β (TGF-β), protein kinase B (AKT), and nuclear factor-κB (NF-κB). Also, the positive effect of MTF-NPs on insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) in heart tissues using immunohistochemical technique is illustrated in the present study. Histopathological examination emphasizes the biochemical findings. The current investigation suggests that MTF-NPs might be considered as a potent novel treatment for the management of cardiac fibrosis and inflammation in patients who receive radiotherapy or workers who may be exposed to gamma radiation. Graphical Abstract

Acute kidney injury (AKI), whether induced by nephrotoxins like glycerol or by gamma radiation, is characterized by severe oxidative stress and subsequent mitochondrial dysfunction. We investigated the protective mechanism of sodium propionate (SP) against AKI in a rat model. Six experimental groups were established: (I) control rats were given saline; (II) rats were administered SP (37.5 mg/kg, p.o.) for two weeks; (III) rats were given an intramuscular injection of glycerol 10 mL/kg body weight; (IV) rats were given glycerol followed by SP treatment for two weeks; (V) rats were exposed to fractionated gamma-radiation (8 Gy; delivered as 2 Gy x 4 times); and (VI) γ-irradiated rats were treated with SP for two weeks. In comparison to AKI rats, SP treatment significantly preserved renal function, reduced serum urea and creatinine, and improved histopathological features. Biochemically, SP reduced lipid peroxidation and protein oxidation (malondialdehyde MDA, protein carbonyl PC, and lipofuscin) while restoring antioxidant defenses as reduced glutathione (GSH) and methionine sulfoxide reductase A (MSRA). SP restored mitophagy flux by increasing microtubule-associated protein light chain 3 (LC3II/LC3I) ratio and PTEN-induced putative kinase 1 (PINK-1) levels, promoting p62 clearance, and downregulating the mitochondrial stress marker, activating transcription factor 5 (ATF5), relative to the untreated AKI groups. These findings demonstrate that SP confers protection against AKI by attenuating oxidative stress and re-establishing mitochondrial quality control through re-establishment of autophagic flux. Hence, SP represents a promising candidate for therapeutic intervention in nephrotoxin- and γ-radiation-induced renal injury.