Evaluating anti-inflammatory and anti-oxidative potentialities of the chloroform fraction of Asparagus racemosus roots against cisplatin induced acute kidney injury

Abstract

Ethnopharmacological relevance: Acute kidney injury (AKI), a global public health concern that increases the risk of death, end-stage renal disease, and prolonged hospital admissions. As of this point, supportive measures like fluid resuscitation and replacement therapy for renal failure are the only treatments available for treating AKI. Asparagus racemosus (AR) also known as Shatavari, belongs to family Liliaceae and is considered exceptional in Ayurvedic medicine due to its versatility in treating and preventing a variety of illnesses.

Aim of the study: The purpose of this study is to determine the effectiveness of chloroform fraction of Asparagus racemosus (CFAR) against cisplatin (CP) induced AKI.

Materials and methods: HPLC was used to analyze the presence of bioactive phytocompounds in CFAR using standard quercetin. Further LC-MS study indicated the existence of different bioactive compounds. Normal Rat Kidney (NRK-52E) cells were used to study the nephroprotective effect of CFAR. Cells were untreated, treated or cotreated with CP (20 μM) and CFAR (5, 25, 50, 100, 200 and 400μg/mL) for 24 h. After 24 h of treatment, cell viability assay and assay of apoptosis parameters were performed. The CFAR at the dose of 50 mg, 100 mg and 200 mg/kg/day was administered orally for 15 days and acute kidney injury was induced in rats by intraperitoneal injection of CP (10 mg/kg body weight) at the 10th day of experimentation. Biochemical studies were performed to evaluate kidney function; protein expression by Western blot and mRNA expression of related gene were studied from the kidney tissues to evaluate the effects of CFAR. Histopathological analysis was done to investigate the structural abnormalities and fibrosis of renal tissues.

Result: Our result reported that CFAR contain many bioactive phytomolecules having many pharmacological properties. Cell viability assay and assay of apoptosis reported that different doses of CFAR could reduced CP-induced cell death and cell apoptosis. The levels of kidney injury markers (BUN, sCr and eGFR), inflammatory markers (Interleukin-18, KIM-1, Cys-C, NF-kB and NGAL), and antioxidant markers (SOD, GSH, CAT, Nrf2 and Bcl2) and lipid peroxidation (MDA) were settled to a normal level by the oral administration of high doses (100 and 200 mg/kg body weight) of CFAR after intraperitoneal injection of CP as suggested by biochemical, histopathological, protein and gene expression studies.

Conclusion: In conclusion, CFAR at the high doses (100 and 200 mg/kg body weight) could able to protect the kidneys from CP induced oxidative stress and inflammation due to presence of bioactive phytomolecules that prevent the activation of oxidative stress induced signalling cascades leading to kidney damage.

Keywords: Acute kidney injury; Asparagus racemosus; Inflammation; Oxidative stress; Phytomolecules.