Radio-protective efficacy of Gymnema sylvestre on Pangasius sutchi against gamma (⁶⁰Co) irradiation

Abstract

Purpose

Freshwater fish Pangasius sutchi was used in this study as a vertebrate model. We evaluated the induction of certain antioxidant enzymes in various vital organs. The radioprotective efficacy of Gymnema sylvestre leaves extract (GS) [25 mg/kg Body Weight (B.W)] and its bioactive compound Gymnemagenin (GG) [0.3 mg/kg B.W] was compared with Amifostine (Ami), the only radioprotector clinically approved by the US-FDA [Ami- 83.3 mg/kg B.W] against different doses of gamma radiation – ⁶⁰Co (Lethal Dose: LD₃₀-9.2 Gy, LD₅₀-10.2 Gy and LD₇₀-11.4 Gy).

Materials and methods

This study was done via stress marker enzymes, cell cycle analysis (CCA) and DNA damage assay prediction with molecular docking, which are reported here for the first time. The results indicate an elevated LPO level and decreased level of CAT, SOD and GSH due to oxidative stress initiation by ⁶⁰Co Ionizing Radiation (IR) on 4th day and slightly reduced on 32nd day while the reverse observed when the fishes were pretreated with Ami, GS and GG. Similarly, CCA and dead/live cells counts were conducted with pretreatment of Ami, GS and GG against ⁶⁰Co IR dose (LD₅₀-10.2 Gy).

Results

In CCA, G0/G1 phase was observed to be the highest in Ami and lowest in GG, against ⁶⁰Co IR doses 10.2 Gy which was 51.76 ± 7.55. The dead cells range observed in pretreated group of Ami, GS and GG was lowest in Ami and highest in GG and live cells (highest in Ami and lowest in GG) as compared to ⁶⁰Co IR group (86.43 ± 3.42 and 8.77 ± 5.95). Thus, antioxidant profile improvement by oxidative stress reduction and gradual progression of different phases of cell cycle except the apoptotic phase along with the live cells counts indicates that the radio-protective efficacy of GS is similar to Ami.

Conclusion

Predictive assessment was carried out by docking of Ami, various components of GS with p53, NF-κβ cells and Rad51 proteins structures responsible for CCA, apoptosis and repair mechanism. These structural proteins were docked with other structural proteins like USP7, TNF-α and partner and localizer of BRCA2 associated (PALB2/BRCA2) complex which made us perform these systemic efforts to find the functional activity of these known radio-protectants.

Keywords:

• Gamma radiation
• amifostine
• Gymnema sylvestre
• gymnemagenin

Disclosure statement

The authors wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Additional information

Funding

Authors wish to thank Director, Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Govt. of India and management of SRMIST, Kattankulathur, Tamil Nadu, India, for providing needed amenities and support for the accomplishment of this work.

Notes on contributors

Pamela Sinha

Dr. Pamela Sinha holds a Doctorate degree in Biotechnology from SRM University, She is mainly involved in aquatic-toxicology, genetic mutation studies for radio-protective activities. Her research interest fetched her numerous publications and a book Chapter. She is also an active member of various national and international scientific association. Currently she is working as Manager in Project management Department of Bioneeds India Private Limited and have more than 2 years of experiences in the same field.

Kantha Devi Arunachalam

Dr. Kantha D. Arunachalam, Dean, Center for Environmental Nuclear Research, SRM Institute of Science and Technology, who have Research and Academic Experience of more than 40 years. Her main research interest on Radiation Biology, Aquatic Toxicology, and Environmental Biotechnology fetched her numerous peer-reviewed research articles, book chapter patents. She was also awarded with many awards and received more than 2 Cr. For her Project funds and she has successfully guided more than 15 PhDs and Post-Doc candidates.

Santhosh Kumar Nagarajan

Santhosh Kumar Nagarajan, Ph.D., who strives to be a protein structural biologist, graduated with a Ph.D. in Bioinformatics from the SRM Institute of Science and Technology, Chennai. His major research interest includes understanding the biophysics behind the functioning of membrane proteins.

Thirumurthy Madhavan

Dr. Thirumurthy Madhavan holds a Doctorate degree in Bioinformatics from Chosun University, South Korea. He is mainly involved in identifying and optimizing lead compounds for diseases such as cancer, asthma, diabetes and hypertension. He has four years of industrial experience in Orchid chemicals & pharmaceutical company. He is presently working as an Associate Professor at SRM Institute of Science & Technology. He has received an young scientist research grant from SERB and established Computational Biology lab at School of Bio-engineering. He has significantly contributed to the scientific fraternity by publishing numerous peer-reviewed research articles.

Arumugam R. Jayakumar

Arumugam R. Jayakumar, Ph.D., is a Scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Miami Miller School of Medicine and a Research Associate Professor at the Miami VA SFVAFRE. His research interests have centered on the liver dysfunction and associated multi-organ dysfunction in various conditions, including rare neurological disorders. His most recent studies focused on the role of liver failure on radiation therapy, as well as the importance of radiation in viral infections, and developing effective medical countermeasures for radiation injuries.

Mohamed Saiyad Musthafa

Dr. M. Saiyad Musthafa, Assistant Professor, P.G. & Research Department of Zoology, The New College (Autonomous) and Laboratory Head – Unit Research in Radiation Biology & Environmental Radioactivity. He has 18 years of Research (in various R&D Institutes) and 10 years of Academic experience in The New College. His main research interest on Radiation Biology, Environmental Radioactivity, Aquatic Toxicology, and Environmental Pollution fetched his numerous peer-reviewed research articles. He was also recognized as a potential and certified reviewer by the editors of Ecotoxicology and Environmental Safety, Aquaculture, Nuclear Science & Technology, Environmental Science and Pollution Research, Fish and Shellfish Immunology and Comparative Biochemistry and Physiology, Part C.