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

Arul Amuthan; Vasudha MD,; Chandrashekara Shreedhara; Venkata Rao; Shiny Jasphin; Nitesh Kumar

Authors

Arul Amuthan aDepartment of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India
Vasudha MD, aDepartment of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India
Chandrashekara Shreedhara bDepartment of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India
Venkata Rao cDepartment of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India
Shiny Jasphin dMelaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India
Nitesh Kumar eDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India

Keywords:

Vernonia cinerea, Astaxanthin, Ayurveda, Siddha, Betulin, Cisplatin, Nephrotoxicity, Nephroprotection

Abstract

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, Nephrotoxicity, Nephroprotection Abbreviations: AF, aqueous fraction; BF, n-butanol fraction; CAE, Crude aqueous extract; EAC, Ehrlich Ascites Carcinoma; GC-MS, Gas Chromatography-Mass Spectroscopy; % ILS, percentage increase in life span; MST, Mean Survival Time; US FDA, Food and Drug Administration of the United States; VC, Vernonia cinerea; WBC, White blood cells

Author Biographies

Arul Amuthan, aDepartment of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India

fDivision of Siddha, Center for Integrative Medicine and Research, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India

Vasudha MD, , aDepartment of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India

Professor and Head