The Possible Protective Effect of Cerium Oxide Nanoparticles on Colistin-Induced Injury in Renal Cortex of Adult Male Albino Rats: Light and Electron Microscopic Study

Introduction: Acute Kidney Injury (AKI) is a rapid decline in renal function. Colistin, a last resort antibiotic for multidrug-resistant infections, is associated with significant nephrotoxicity. Cerium oxide nanoparticles (CeONPs) are potent scavengers of reactive oxygen species (ROS), exhibiting antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects of CeONPs against colistin-induced renal damage in adult male albino rats. materials and methods: Background & Aims: Acute Kidney Injury (AKI) is a syndrome characterized by sudden and rapid deterioration of renal function. Colistin, one of polypeptide antibiotics (polymyxin E), is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Cerium oxide nanoparticles efficiently scavenge ROS, it is the reason for the antioxidant properties, anti-inflammatory effect and also a potential reno-protective effect. This work aimed at studying the possible protective effect of cerium oxide nanoparticles (CONPs) against colistin induced injury on renal cortex in adult male albino rats. Methods: Forty-eight adult male albino rats about 3 months old and with average weight (200 - 250 grams) were classified into four groups, each group formed of 12 rats as follow: Group I (control group), Group II (cerium oxide nanoparticles treated group (CONPS)), Group III (colistin treated group) and Group IV (CONPS and colistin). The experimental period was 10 days and at the end of the experimental periods, the animals were sacrificed and kidneys were dissected and processed for further histological examination. Results: Colistin-treated rats (Group III) revealed disturbed bush border, cytoplasmic vacuolations and pykontic nuclei of cells lining renal tubules. Luminal eosinophilic material, inflammatory cellular infiltration and congested blood vessels were observed. Electron microscopic examination revealed loss of apical microvilli, cytoplasmic vacuoles, dense bodies and disturbed palisade arrangement of mitochondria. Elevated NF-κB expression and elevated biochemical markers of renal dysfunction were detected. Conversely, the CONPs + colistin group (Group IV) showed marked preservation of the general histological structure and ultrastructure of the renal cortex, reduced NF-κB expression and normalized renal function markers. Conclusion: Cerium oxide nanoparticles exhibit notable nephroprotective effects against colistin-induced AKI through their antioxidant and anti-inflammatory properties. These findings suggest CONPs as a promising therapeutic adjunct to reduce nephrotoxicity in patients requiring colistin treatment. Methods: Forty-eight adult male albino rats were equally divided into four groups: Group I (Control), Group II (CeONPs), Group III (Colistin), and Group IV (CeONPs + Colistin). At the end of the experiment, blood samples were collected to assess renal function by measuring serum urea and creatinine. Kidney tissue was processed for histological examination and immunohistochemical staining to evaluate the expression of the inflammatory marker for nuclear factor Kappa B (NF-κB). Aims: Acute Kidney Injury (AKI) is a syndrome characterized by sudden and rapid deterioration of renal function. Colistin, one of polypeptide antibiotics (polymyxin E), is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Cerium oxide nanoparticles efficiently scavenge ROS, it is the reason for the antioxidant properties, anti-inflammatory effect and also a potential reno-protective effect. This work aimed at studying the possible protective effect of cerium oxide nanoparticles (CONPs) against colistin induced injury on renal cortex in adult male albino rats. Methods: Forty-eight adult male albino rats about 3 months old and with average weight (200 - 250 grams) were classified into four groups, each group formed of 12 rats as follow: Group I (control group), Group II (cerium oxide nanoparticles treated group (CONPS)), Group III (colistin treated group) and Group IV (CONPS and colistin). The experimental period was 10 days and at the end of the experimental periods, the animals were sacrificed and kidneys were dissected and processed for further histological examination. Results: Colistin-treated rats (Group III) revealed disturbed bush border, cytoplasmic vacuolations and pykontic nuclei of cells lining renal tubules. Luminal eosinophilic material, inflammatory cellular infiltration and congested blood vessels were observed. Electron microscopic examination revealed loss of apical microvilli, cytoplasmic vacuoles, dense bodies and disturbed palisade arrangement of mitochondria. Elevated NF-κB expression and elevated biochemical markers of renal dysfunction were detected. Conversely, the CONPs + colistin group (Group IV) showed marked preservation of the general histological structure and ultrastructure of the renal cortex, reduced NF-κB expression and normalized renal function markers. Conclusion: Cerium oxide nanoparticles exhibit notable nephroprotective effects against colistin-induced AKI through their antioxidant and anti-inflammatory properties. These findings suggest CONPs as a promising therapeutic adjunct to reduce nephrotoxicity in patients requiring colistin treatment. Results: Colistin administration in Group III resulted in significant renal impairment, characterized by elevated serum urea and creatinine, severe histopathological damage (including tubular necrosis), and a marked increase in NF-κB expression. In contrast, rats pre-treated with CeONPs (Group IV) demonstrated significantly improved kidney function tests, a substantial reduction in histopathological lesions, and a notable decrease in NF-κB expression compared to the colistin group. discussion: Background & Aims: Acute Kidney Injury (AKI) is a syndrome characterized by sudden and rapid deterioration of renal function. Colistin, one of polypeptide antibiotics (polymyxin E), is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Cerium oxide nanoparticles efficiently scavenge ROS, it is the reason for the antioxidant properties, anti-inflammatory effect and also a potential reno-protective effect. This work aimed at studying the possible protective effect of cerium oxide nanoparticles (CONPs) against colistin induced injury on renal cortex in adult male albino rats. Methods: Forty-eight adult male albino rats about 3 months old and with average weight (200 - 250 grams) were classified into four groups, each group formed of 12 rats as follow: Group I (control group), Group II (cerium oxide nanoparticles treated group (CONPS)), Group III (colistin treated group) and Group IV (CONPS and colistin). The experimental period was 10 days and at the end of the experimental periods, the animals were sacrificed and kidneys were dissected and processed for further histological examination. Results: Colistin-treated rats (Group III) revealed disturbed bush border, cytoplasmic vacuolations and pykontic nuclei of cells lining renal tubules. Luminal eosinophilic material, inflammatory cellular infiltration and congested blood vessels were observed. Electron microscopic examination revealed loss of apical microvilli, cytoplasmic vacuoles, dense bodies and disturbed palisade arrangement of mitochondria. Elevated NF-κB expression and elevated biochemical markers of renal dysfunction were detected. Conversely, the CONPs + colistin group (Group IV) showed marked preservation of the general histological structure and ultrastructure of the renal cortex, reduced NF-κB expression and normalized renal function markers. Conclusion: Cerium oxide nanoparticles exhibit notable nephroprotective effects against colistin-induced AKI through their antioxidant and anti-inflammatory properties. These findings suggest CONPs as a promising therapeutic adjunct to reduce nephrotoxicity in patients requiring colistin treatment. Discussion: Colistin induces AKI through increased membrane permeability, oxidative damage, and acute tubular necrosis. This oxidative stress upregulates inflammatory mediators like NF- κB, exacerbating tissue injury. The renoprotective effect of CeONPs is attributed to their unique ability to switch between Ce³⁷ and Ce³⁷ oxidation states, allowing continuous ROS scavenging. By reducing oxidative stress, CeONPs also suppress the NF-κB-mediated inflammatory pathway. Aims: Acute Kidney Injury (AKI) is a syndrome characterized by sudden and rapid deterioration of renal function. Colistin, one of polypeptide antibiotics (polymyxin E), is essential for treating multidrug-resistant Gram-negative bacterial infections but has significant nephrotoxic side effects. Cerium oxide nano