Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice.

Abstract

Incidence and prevalence of cancer is an alarming situation globally. For the treatment of cancer many anticancer drugs have been developed but, unfortunately, their potential cardiotoxic side effects raised serious concerns about their use among clinicians. Cyclophosphamide is a potent anticancer and immunosuppressant drug but its use is limited due to cardiotoxic side effect. Thus, there is a need for the development of certain drug which can reduce cardiotoxicity and can be used as an adjuvant therapy in cancer patients. In this direction we, therefore planned to evaluate nerolidol (NER) for its cardioprotective potential against cyclophosphamide-induced cardiotoxicity in Swiss Albino mice. Animals were divided into 6 groups. Vehicle control; Cyclophosphamide (CP 200); NER 400 per se; NER 200 + CP 200; NER 400 + CP 200; and fenofibrate (FF 80) + CP 200. Dosing was done for 14 days along with a single dose of CP 200 on the 7th day. On 15th day animals were sacrificed and various biochemical parameters pertaining to oxidative stress, nitrative stress, inflammation, apoptosis and fibrosis were estimated in the blood and heart tissues. Histopathological analysis (H & E and Masson's trichrome staining); ultrastructural analysis (transmission electron microscopy) and immunohistochemical analysis were also performed along with mRNA expression and molecular docking to establish the cardioprotective potential of nerolidol. Nerolidol acted as a potent cardioprotective molecule and attenuated CP-induced cardiotoxicity.

• Authors: Ashif Iqubal, Sumit Sharma, Mohd Asif Ansari, Abul Kalam Najmi, Mansoor Ali Syed, Javed Ali, M Mumtaz Alam, Shaniya Ahmad, Syed Ehtaishamul Haque
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 863 Pg. 172666 (Nov 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 31541628 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• CCN2 protein, mouse
• RNA, Messenger
• Sesquiterpenes
• Transcription Factor RelA
• Transforming Growth Factor beta1
• Connective Tissue Growth Factor
• Nitric Oxide
• Cyclophosphamide
• Catalase
• Nitric Oxide Synthase Type II
• Glutathione
• nerolidol

Topics

• Animals
• Apoptosis (drug effects)
• Catalase (metabolism)
• Connective Tissue Growth Factor (genetics)
• Cyclophosphamide (adverse effects)
• Fibrosis
• Gene Expression Regulation (drug effects)
• Glutathione (metabolism)
• Heart (drug effects)
• Inflammation (chemically induced, drug therapy, metabolism, pathology)
• Male
• Mice
• Molecular Docking Simulation
• Myocardium (metabolism, pathology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics)
• Oxidative Stress (drug effects)
• RNA, Messenger (genetics)
• Sesquiterpenes (metabolism, pharmacology, therapeutic use)
• Transcription Factor RelA (chemistry, metabolism)
• Transforming Growth Factor beta1 (genetics)