Protective Effect of Exacum lawii on Cisplatin-induced Oxidative Renal Damage in Rats

摘要

Background: Exacum lawii (Gentianaceae), a bitter herb conventionally used in kidney diseases and eye problems, endemic to the Western coast and Southern part of India. Aim: Folklore reports encourage the author to explore the nephroprotective effect of the standardized ethanolic extract of E. lawii against cisplatin-induced renal toxicity in the rat to scientifically validate its traditional use. Materials and Methods: Ethanolic extract of the whole plant of E. lawii was standardized with swertiamarin (secoiridoid glycoside) using high-performance liquid chromatography and tested for subacute toxicity according to the OECD guidelines. Nephroprotective potential at different doses of extract was evaluated against cisplatin (6 mg/kg, intraperitoneal) in experimental rats. The changes in serum renal toxicity markers, renal tissue oxidative stress biomarkers, and proinflammatory cytokines level were measured. To estimate the change in oxidative status of renal tissues, DNA and single viable cells were isolated from treated rat kidney, DNA fragmentation assay and flow cytometric analysis of reactive oxygen species (ROS) were performed. Histopathology of renal tissues was also examined. Results: Swertiamerin was found to be 119.59 mg/g of extract. Administration of E. lawii extract (ELE) restored the biochemical parameters. It also decreases the elevated proinflammatory cytokines level in kidney tissues and protected rat kidneys from oxidative stress in rats. Nephroprotective activity was validated by estimating ROS production in kidney live cells and DNA damage in kidney tissue. The histological architecture was also conserved. Conclusion: ELE showed significant renal protection against cisplatin through reducing oxidative stress and inflammation. SUMMARY High-performance liquid chromatography standardisation of Exacum lawii extract with Swertiamerin and its subacute toxicity study Nephroprotective activity of Exacum lawii extract and Swertiamerin was evaluated in cisplatin-induced model and justified by various biochemical parameters and histopathological study Role of oxidative stress in cisplatin-induced nephrotoxicity was confirmed by measuring levels of antioxidant markers and proinflammatory cytokines in rat renal tissues, ROS estimation by flow cytometry and DNA fragmentation assay by gel electrophoresis in renal cells. Abbreviations used: ELE: Exacum lawii ethanolic extract; WHO: World Health Organization; SOD: Superoxide dismutase; CAT: Catalase; MDA: Malondialdehyde; HPTLC: High performance thin layer chromatography; p.o.: Per oral; i.p.: Intraperitoneal; TNF-α: Tumor necrosis factor alpha; IL-1β: Interleukin 1 beta; IL-6: Interleukin 6; ROS: Reactive oxygen species.