Comparison of the nephroprotective effect of [6]-gingerol and the [6]-gingerol-β-cyclodextrin complex against...

Cisplatin is an antineoplastic agent effective for the treatment of several cancers. However, due to its nephrotoxicity, its use is limited. Acute kidney injury (AKI) induced by cisplatin is caused by inflammation, apoptosis, and oxidative stress in renal tubular cells. Natural compounds derived from ginger (Zingiber officinale) such as [6]-gingerol, possess anti-inflammatory and antioxidant properties. This study explores the protective effects of [6]-gingerol and its β-cyclodextrin complex ([6]-gingerol-β-CD) on cisplatin-induced AKI in mice. We hypothesize that complexing [6]-gingerol with β-cyclodextrin would enhance its solubility and reduce its pungency, making it more suitable for clinical use. Additionally, we aim to determine whether β-cyclodextrin complexation can improve the oral bioavailability of [6]-gingerol without compromising its therapeutic efficacy. The minimum dose of cisplatin required to induce AKI was determined to be 15 mg/kg. Female Swiss mice (n = 6-8) were divided into four groups: control, cisplatin (15 mg/kg), [6]-gingerol (12.5 mg/kg), and [6]-gingerol-β-CD (12.5 mg/kg). The treatments were administered orally for 5 days. On the third day, cisplatin was administered intraperitoneally (i.p.), and the animals were euthanized after 5 days. All biochemical parameters investigated, such as plasma urea and creatinine, urinary gamma GT, urinary protein, MPO, and GSH were altered by cisplatin. The parameters evaluated in this study were categorized into renal function, inflammation, and oxidative stress. Both [6]-gingerol and complexed gingerol effectively restored most of the evaluated parameters to control levels. Following these analyses, we investigated the JAK/STAT pathway and observed that gingerol deactivates this pathway, thereby preventing cisplatin-induced nephrotoxicity. In conclusion, β-CD complexation did not interfere with [6]-gingerol therapeutic, emphasizing its indication for future clinical tests. Further analysis showed that [6]-gingerol prevented cisplatin nephrotoxicity by deactivating JAK/STAT signaling pathway.