Eicosapentaenoic Acid Silica Nanoemulsion Protects Against in vivo Drug-Induced Nephrotoxicity

Background: Nephrotoxicity is the hallmark of anti-neoplastic drug metabolism. It causes oxidative stress and is associated with considerable morbidity and mortality. Eicosapentaenoic acid (EPA), an omega-3 fatty acid with anti-inflammatory and antioxidant properties, may reduce organ toxicity associated with chemotherapy. Objective: We hypothesized that EPA, particularly when loaded into a silica nanoemulsion to enhance stability and bioavailability, would protect against cisplatin-induced nephrotoxicity. Methods: Forty rats were divided randomly into five groups: Group I (control group): healthy rats received a vehicle. Group II (EPA): healthy rats received EPA. Group III (cisplatin group): healthy rats received cisplatin. Group IV (treated group I): healthy rats received cisplatin before receiving EPA. Group V (treated group II): healthy rats received cisplatin and EPA silica nanoemulsion. After the experimental period, serum was separated to determine urea and creatinine. In addition, blood urea nitrogen (BUN) was calculated. Also, kidney homogenate was used to detect the reduced glutathione (GSH), malondialdehyde (MDA), and total antioxidant capacity (TAC) using a colorimetric method. While high-performance liquid chromatography (HPLC) was used to find out the amounts of erythrocyte membrane fatty acids and urine 8-hydroxy-2-deoxyguanosine (8-OHdG), additionally, histopathological investigations were carried out to confirm our hypothesis. Results: Our data showed that there was a significant increase in creatinine, BUN, MDA, 8-OHdG, arachidonic acid (AA), and linoleic acid (LA) concomitant with a significant reduction in GSH, TAC, and alpha-linolenic acid (ALA) in cisplatin group when compared to the control group. Additionally, our findings displayed a significant decrease in creatinine, BUN, MDA, 8-OHdG, AA, and LA associated with a significant increase in GSH, TAC, and ALA in all treated groups when compared with the cisplatin group. However, an improbable progress was detected between the treated group I, and the treated group II. These biochemical outcomes were supported by the histopathological results. Conclusion: The study revealed that EPA silica nanoemulsion could play a beneficial role in the management of nephrotoxicity caused by chemotherapy drugs while treating various types of cancers.