Almond oil attenuates etoposide-induced hematological disorders and hepatorenal toxicity associated with oxidative injuries, upregulated caspase-3, and DNA damage in male rats

Etoposide (ETP) is a widely used chemotherapeutic medication for treating numerous types of malignant tumors. However, it remains unclear whether almond oil (AO) can protect against hemato-biochemical toxicities of ETP in rats. Therefore, this study aimed to assess the efficacy of AO against ETP-induced hematological and hepatorenal alterations in a murine model. Male rats were intraperitoneally injected with ETP (1 mg/kg bw) alone or with oral administration of AO (800 mg/kg bw) for 6 weeks. In rats intoxicated with ETP, treatment with AO reversed the decrease in hemoglobin content, lymphocyte%, and eosinophil%, but did not significantly affect the reductions in red blood cells count, platelets count, total white blood cells count, neutrophil%, and monocyte%. AO therapy improved ETP-induced perturbations in the liver and kidney, significantly regulated serum levels of alanine aminotransferase, aspartate aminotransferase, albumin, urea, and creatinine, and preserved the histoarchitecture of liver and kidney tissues to near-normal state. In addition, AO efficiently abolished oxidative stress induced by ETP in the liver and kidney, as seen in the reduced level of malondialdehyde, and increased catalase, superoxide dismutase, and glutathione (GSH) tissue levels (except liver GSH). Furthermore, AO reduced the elevated levels of apoptotic marker (caspase-3) observed in ETP-exposed rats. Notably, in rats exposed to ETP, AO administration resulted in a significant inhibition of hepatic and renal comet parameters, an indication of less DNA damage. Multivariate principle component analysis further supported a strong discrimination between the ETP and ETP + AO groups. Overall, the current study showed that AO counteracted the ETP toxic effects by modulating oxidative stress, cell apoptosis, and DNA damage. Therefore, AO could be used as a natural adjuvant to enhance the safety and tolerability of ETP chemotherapy. • First attempt to investigate the effect of AO on ETP-induced toxicity in murine model. • AO relived hematological disorders and immunosuppression. • AO regulated hepatic and kidney functional biomarkers. • AO suppressed lipid peroxidation and boosted the antioxidant defense levels. • AO inhibited the apoptotic protein (caspase-3) and DNA damage induced by ETP.