Journal of Environmental Pathology, Toxicology and Oncology, 36(2):113–119 (2017) 113 0731-8898/17/$35.00 © 2017 Begell House, Inc. www.begellhouse.com Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of Moralbosteroid, a Steroidal Glycoside Gaurav Gupta, a,b, * Dinesh Kumar Chellappan, c Irene Satiko Kikuchi, d Terezinha de Jesus Andreoli Pinto, d Kavita Pabreja, b Mohit Agrawal, e Yogendra Singh, a Juhi Tiwari, a & Kamal Dua f a Jaipur National University, School of Pharmaceutical Sciences, Jagatpura, 302017, Jaipur, India; b University of Newcastle, School of Medicine and Public Health, Newcastle, NSW 2308, Australia; c International Medical University, School of Pharmacy, Kuala Lumpur, 57000, Malaysia; d University of São Paulo, Department of Pharmacy, Faculty of Pharmaceutical Sciences, São Paulo, Rua Professor Lineu Prestes 05508-000, Cidade Universitária, Brazil; e Suresh Gyan Vihar University, School of Pharmacy, Jagatpura, 302017, Jaipur, India; f Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo NSW 2007, Australia *Address all correspondence to: Dr. Gaurav Gupta, University of Newcastle, School of Medicine and Public Health, Newcastle, NSW 2308, Australia; Tel.: +61 0410295637, E-mail: gauravpharma25@gmail.com ABSTRACT: Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Signi- ficant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential. KEY WORDS: moralbosteroid, antioxidant, oxidative stress, nephrotoxicity, paracetamol I. INTRODUCTION Recent studies have shown that there is a gen- eral fear of risk involved with use of both natural and synthetic agents. It is now believed that these agents, although therapeutic by action, can present with fatal adverse reactions. There is considerable attention now on long-term use of these agents, as they have the highest risk associated with nephro- toxicity. 1 This is also the key purpose of elimination of such drugs from the marketplace and termination of their development. 2 Paracetamol (PCM) is extensively used for the treatment of pain and fever. It is contained in many formulations, offered both over the counter and by prescription. Because of its wide range of accessi- bility combined with its comparative toxicity, there is potentially a higher probability of unwanted re- actions. 3 Toxic levels of PCM can damage most of the vital parts of the kidneys. This eventually leads to acute, sometimes fatal, renal failure. Individuals with impaired kidney function can accumulate toxic potential even at the usual therapeutic doses of PCM and other similar drugs. 4 Currently numerous research studies are ongo- ing across the globe in search of substances that protect the kidneys and other vital body organs from such damages. 5–7 Moralbosteroid is a steroidal glycoside moiety isolated in our laboratory from the bark of Morus alba. It is basically related to β-sitosterol, lawsaritol, and stigmasterol. 8 Moralbosteroid has been reported as a protec-