Asparagus falcatus L. (Asparagaceae) leaf extracts attenuate doxorubicin-induced renal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways

Abstract

The search for therapeutic agents that improve kidney function against doxorubicin-induced renal toxicity is important. Herein, the potential nephroprotective activity by Asparagus falcatus L. (AF, Asparagaceae) leaf extracts against doxorubicin-induced renal toxicity (5 mg/kg, ip) in Wistar rats (n = 6/group) after oral administration of hexane (55 mg/kg), ethyl acetate (35 mg/kg), butanol (75 mg/kg), and aqueous (200 mg/kg) extracts of AF for 28 consecutive days was investigated. It was noticed that the treatment with the selected extracts of AF significantly attenuated doxorubicin-induced elevations of serum creatinine, urea nitrogen, β₂-microglobulin, cystatin C, and proteinuria in experimental rats. The histology showed attenuation of the features of acute tubular injury. Treatment regimens significantly reversed the doxorubicin-induced reduction in total antioxidant status, glutathione peroxidase, and glutathione reductase activity in renal tissue homogenates. A suppression in lipid peroxidation was noted with hexane, ethyl acetate, and butanol extracts of AF. Moreover, a reduction in the concentration of the pro-inflammatory mediator TNF-α (p < 0.05), and immunohistochemical expression of COX-2 were observed. The immunohistochemical expression of pro-apoptotic Bax protein was decreased and the anti-apoptotic BCL-2 was increased in renal tissues following the treatments. In conclusion, it was revealed that, hexane, ethyl acetate, butanol, and aqueous extracts of AF attenuate doxorubicin-induced renal toxicity in Wistar rats through antioxidant, anti-inflammatory, and anti-apoptotic pathways. The plant, AF could be recommended as a promising therapeutic agent to minimize renal toxicity induced by doxorubicin in cancer patients, however, subsequent clinical trials are warranted.

Graphical Abstract

Keywords:

• Anti-apoptotic effects
• anti-inflammatory effects
• antioxidant potential
• Asparagus falcatus
• doxorubicin
• renal toxicity

Acknowledgement

The authors thank the technical staff of the Departments of Biochemistry and Pathology, Faculty of Medicine, University of Ruhuna, for providing technical support. Further, the authors would be grateful to Senior Professor Gamini Fonseka, Department of English & Linguistics, University of Ruhuna, Sri Lanka for providing the service of English language editing.

Disclosure statement

The authors report that there is no conflict of interest.

Additional information

Funding

This work was supported by the Error! Hyperlink reference not valid. [RG/2016/HS-03] and the University Grants Commission special allocation to strengthen the research grant [RU/PG- R/16/14].