Cyclophosphamide (CYP) is a potent DNA-interactive anticancer drug; however, its clinical drawbacks are chiefly associated with induction of oxidative multi-organ toxicity. Sitagliptin (STG) is an antidiabetic dipeptidyl peptidase-4 inhibitor drug with antioxidant efficacy. Herein, we have explored whether STG could abrogate the CYP-induced oxidative stress-mediated cardiac and hepatorenal toxicities in male rats. Sitagliptin (20 mg/kg, o.p) was administered to rats for 5 consecutive days against organ toxicities induced by CYP (200 mg/kg, i.p) on day 5 only. CYP induced marked injuries in the liver, kidney and heart underscored by prominent increases in serum activities of ALT, AST, LDH, creatine kinase and levels of urea, uric acid and creatinine, while albumin level significantly decreased compared to normal control rats. Further, CYP considerably reduced the activities of SOD, CAT, GPx, and levels of GSH, whereas MDA level increased significantly in comparison to control rats. These biochemical alterations were confirmed by multiple histopathological lesions in the tissues. Interestingly, the STG pretreatment abrogated the biochemical and histopathological changes induced by CYP. These results provide first evidence that repurposing STG may protect the liver, kidney and heart from the oxidative deterioration associated with CYP chemotherapy.
Antioxidants , Dipeptidyl-Peptidase IV Inhibitors , Heart , Sitagliptin Phosphate , Animals , Antioxidants/pharmacology , Cyclophosphamide/toxicity , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Heart/drug effects , Kidney/drug effects , Liver/drug effects , Male , Oxidative Stress , Rats , Sitagliptin Phosphate/pharmacology
BACKGROUND: Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid agent whose efficacy is limited by marked organ toxicities associated with oxidative stress. The study investigated beneficial effect of virgin coconut oil (VCO) supplementation on MTX-induced oxidative stress and inflammation in rats. METHODS: Rats were divided into 4 groups (n = 6): Control, MTX (20 mg/kg bw), VCO (5%) + MTX and VCO (15%) + MTX. The pre-treatment with VCO for 14 days was followed by single intraperitoneal injection of MTX and the rats were sacrificed after 3 days. Serum activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were determined. Interleukin-6 (IL-6), C-reactive protein (CRP) and nitric oxide (NO) levels were also evaluated. RESULTS: MTX induced a distinct diminution in serum activities of oxidative stress markers (SOD, CAT, GPx and GSH), while lipid peroxidation considerably increased demonstrated by MDA level. Similarly, levels of IL-6, CRP and NO increased prominently in MTX control rats. The VCO supplementation markedly enhanced resistance to the MTX-induced biochemical alterations in rats. CONCLUSION: VCO can be a useful adjuvant natural product in MTX chemotherapy by reducing oxidative stress and pro-inflammatory responses.
