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 tox icity 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 ¼ 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 eleva tions of serum creatinine, urea nitrogen, b2-microglobulin, cystatin C, and proteinuria in experimental rats. The histology showed attenuation of the features of acute tubular injury. Treatment regimens sig nificantly reversed the doxorubicin-induced reduction in total antioxidant status, glutathione peroxid ase, 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 concen tration of the pro-inflammatory mediator TNF-a (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 con clusion, 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-apop totic 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 war ranted.