Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity

Abstract

Background: Traditional Siddha Medicine advises using metal-based formulations to treat cancers. In the case of any toxicities during the therapy, Siddha physicians use Vernonia cinerea (VC) whole plant kashayam (crude aqueous extract-CAE) to reverse the toxic effects. Aim: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin. Materials and methods: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated. Result: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%–75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin. Conclusion: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.

Keywords

• Vernonia cinerea
• Astaxanthin
• Ayurveda
• Siddha
• Betulin
• Cisplatin