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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 - 60 Co (Lethal Dose: LD 30 -9.2   Gy, LD 50 -10.2   Gy and LD 70 -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 60 Co 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 60 Co IR dose (LD 50 -10.2   Gy)., Results: In CCA, G0/G1 phase was observed to be the highest in Ami and lowest in GG, against 60 Co 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 60 Co 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.

Exposure to ionizing radiation is harmful to any living organism. It may cause varying levels of genetic mutation or ultimately death. Synthetic compounds have been used to counteract the hazardous effect of radiation on the live cells, but the possibility of these synthetic compounds being harmful to the organism being treated also exists. Herbal formulations are thus being explored as a possible alternative for the synthetic radioprotectant. Induction of DNA damage in fishes caused by ionizing radiation and its protection by phytocompounds is a hardly studied topic. In this study, we analyzed the radioprotective effect of Gymnema sylvestre leaves extract (GS) and its active compound gymnemagenin (GG) against different doses of gamma radiation ( 60 Co) on the freshwater fish Pangasius sutchi. The radioprotective efficacy was assessed by micronuclei and alkaline comet assays. The freshwater fish P. sutchi was pre-treated with intramuscular injection (IM) of amifostine (83.3 mg/kg of B.W.), GS (25 mg/kg of B.W.) and GG (0.3 mg/kg of B.W.), 1 h prior to the gamma radiation. The fishes were exposed to LD 30 , LD 50 and LD 70 of gamma radiation and the protection activities were assessed by analyzing the number of micronuclei (MN) and erythrocytic abnormalities in the blood after 2, 4, 8, 16 and 32 days after exposure. Compared to the irradiated fishes, frequency of erythrocytic abnormalities were decreased in response to the radio-protection in the amifostine treated groups for all three doses of gamma radiation (LD 70 - 77.62%), (LD 50 - 80.11%) and (LD 30 - 82.30%); GS (LD 70 - 62.66%), (LD 50 - 69.74%) and (LD 30 - 70.81%); and GG (LD 70 - 49.42%), (LD 50 - 53.43%) and (LD 30 - 58.42%). Similarly, a significant radio-protective effect in terms of decremented DNA damage was observed using the comet assay after post exposure. The percentage of protection noted for amifostine was (LD 70 - 58.68%), (LD 50 - 64.52%) and (LD 30 - 74.40%); GS (LD 70 - 53.84%), (LD 50 - 59.02%) and (LD 30 - 65.97%); GG (LD 70 - 49.85%), (LD 50 - 52.56%) and (LD 30 - 64.30%). From the current study, we can conclude that the radioprotective efficacy of the GS is similar to the synthetic compound (amifostine) and also greater than the bioactive compound (GG). The synergetic effect of the plant extract which leads to a better protection than the bioactive compound must be further studied. MN and Comet assays can easily identify the damage due to radiation exposure and thus can be used as predictive biomarkers for aquatic organisms exposed to radiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The early biomarkers for the hematological, serological and histological alterations due to the effect of ½ and ¼ LC 50 of 238 U in different organs in freshwater fish Pangasius sutchi for water-borne 238 U accumulation was investigated. The toxicological data due to 238 U accumulation on the hematological parameters such as hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and hematocrit (Hct) to evaluate the oxygen carrying capacity has been indicated as the secondary response of the organisms. The biomarkers of liver damage were determined as by Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), Alkaline Phosphatase (ALP), γ-Glutamyl Transferase (γ-GT). Similarly, the renal biomarkers of kidney damage were accessed by creatinine, uric acid, triglycerides, and cholesterol. The decrease in hemoglobin in the experimental group due to disturbed synthesis of hemoglobin was directly proportional to the concentration and exposure duration of 238 U. The histological studies proved that liver and gills are the target organ for 238 U toxicity. The extensive histological lesions were observed in various tissues due to oxidative stress by the accumulation of 238 U, and the 238 U toxicity in the organs was in the order of Gills238 U toxicity to assess fish health in Uranium ( 238 U) biomonitoring programs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The strategic plan of this study is to analyze any possible radiological impact on aquatic organisms from forthcoming uranium mining facilities around the Nagarjuna Sagar Dam in the future. The predominantly consumed and dominant fish species Pangasius sutchi, which is available year-round at Nagarjuna Sagar Dam, was selected for the study. To comprehend the outcome and to understand the mode of action of 238 U, the fish species Pangasius sutchi was exposed to ¼ and ½ of the LC 50 doses of waterborne 238 U in a static system in duplicate for 21 days. Blood and organs, including the gills, liver, brain and muscles, were collected at different time periods-0h, 24h, 48h, 72h, 96h, 7, days 14days and 21 days-using ICP-MS to determine the toxic effects of uranium and the accumulation of 238 U concentrations. The bioaccumulation of 238 U in P. sutchi tissues was dependent on exposure time and concentration. The accumulation of uranium was, in order of magnitude, measured as gills>liver>brain>tissue, with the highest accumulation in the gills. It was observed that exposure to 238 U significantly reduced antioxidant enzymes such as superoxide dismutase, catalase, and lipid peroxidase. The analysis of DNA fragmentation by comet assay and cell viability by flow cytometry was performed at different time intervals. DNA histograms by flow cytometry analysis revealed an increase in the G2/M phase and the S phase. The long-term 238 U exposure studies in fish showed increasing micronucleus frequencies in erythrocytes with greater exposure time. The higher the concentration of 238 U is, the greater is the effect observed, suggesting a close relationship between accumulation and toxicity. A possible ROS-mediated 238 U toxicity mechanism and antioxidant responses have been proposed., (Copyright © 2017 Elsevier B.V. All rights reserved.)