AMELIORATION OF 131I INDUCED SALIVARY GLAND DAMAGE BY OCIMUM SANCTUM AND AMIFOSTINE PRE SUPPLEMENTATION IN RABBITSHTML Full Text
AMELIORATION OF 131I INDUCED SALIVARY GLAND DAMAGE BY OCIMUM SANCTUM AND AMIFOSTINE PRE SUPPLEMENTATION IN RABBITS
Bhartiya *, Y. Pawar, L. Joseph, Y. Raut, D’ Souza S., D. Singh, S. Awasare, Y. Nayak, R. Hawaldar and S. Banerjee
Radiation Medicine Centre *, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India.
ABSTRACT: Oral administration of 131I to the patients of differentiated thyroid cancer is routinely used to ablate remnant thyroid tissue or metastasis. In 30% of the patients, permanent salivary gland damage due to therapeutic 131I exposure results in xerostomia, affecting their quality of life. Amifostine is the only standard FDA-approved radio protect ant available for damage control, albeit associated with side effects such as hypotension and allergic reactions. The present study was carried out to compare the radioprotective effect of O. sanctum extract with that of a standard radio protectant, amifostine in salivary glands of the rabbits exposed to high dose (1GBq) of 131I internal radiation exposure. The study parameters included were salivary amylase, serum SGOT and SGPT, haematological parameters, 99m Technetium pertechnetate scintigraphy study, histopathology and ultrastructure of the salivary gland. The experimental rabbits were sacrificed after 6 months of 131I exposure. The experimental observations, majorly histopathological and electron microscopic are suggestive of better preservation of cell morphology and ultrastructure after O. santum as well as amifostine pre supplementation. This indicates the beneficial effects of O. sanctum extract pre supplementation for the radioprotection of salivary gland against therapeutic 131I exposure.
Keywords: 131Iodine, O. sanctum extract, amifostine, salivary glands, radioprotection, xerostomia
INTRODUCTION: Effective management of differentiated thyroid carcinoma involves 131I oral administration for ablating the remnant thyroid tissue and treating recurrent disease 1.
Though it is mostly concentrated in the thyroid gland, patients receive whole-body internal radiation exposure. In case of recurrence, whole-body exposure increases further due to repeated administration of 131I depending on the disease severity.
Though the therapeutic dose administered is designed with all precautions ensuring the patient's safety, few side effects such as transient anaemia, transient salivary gland swelling, pulmonary fibrosis and hepatotoxicity are observed in this patient population 2, 3. In about 20-25% of thyroid cancer patients receiving therapeutic 131I exposure, salivary gland damage of permanent nature is observed, leading to xerostomia and other dental problems affecting their quality of life 3, 4. It has been observed that other than the thyroid, the salivary glands are another major receiving port for concentrating 131I, as it also shows the presence of sodium iodide symporter, which helps in transporting 131I from blood to inside of thyrocytes 5. This particularly is a cause of concern for 131I treated patients as they have to bear the discomforts of the dry mouth for the rest of their life. The strategies planned for ameliorating the salivary gland damage either improve the transit time of 131I by using sour candies such as lemon candy, or using sialogogues such as pilocarpine, or controlling the cellular damage with the help of radio-protectants 6, 7.
So far, amifostine is the only FDA-approved radio protectant which has been used in clinical settings for salivary gland radioprotection in case of 131I and external radiation exposure in the management of thyroid and head and neck cancer 8. However, effective amifostine administration has led to hypotension in patients. Therefore, it needs to be administered under medical supervision 9. This indicates the need of a still better choice of radio protectant for use in the patient population. Clinical reports of discontinuation of the drug in patients due to adverse effects are available in literature 9, 10. Many natural dietary components and herbal products are under exploration for their usage as radio protectant 11, 12. O. sanctum (Ocimum sanctum) i.e. Tulasi extract, has been extensively investigated for its radioprotective abilities against external gamma irradiation by Uma Devi et al. 13, 14.
It is also known for its antioxidant, anti-inflammatory, hepatoprotective, and many other beneficial properties 15, 16. Previous work of our group has demonstrated the radioprotective ability of the Tulasi extract against internal therapeutic 131I exposure of 3.7 MBq and 18.5 MBq of 131I in mice and rats, respectively, indicating a beneficial effect on the salivary gland damage 17, 18. In the present study, we have compared the effect of O. sanctum and amifostine pre supplementation on the salivary glands after high dose 131I exposure in higher animals i.e., rabbits.
MATERIALS AND METHOD:
Animal Experiment: The project was approved by Institutional Animal (Project Ethics Committee No BAEC/21/10) 11. Male New-Zealand white rabbits weighing around 1-1.5 kg were maintained in the Institutional animal house under controlled temperature, humidity, and light cycle with free access to water and a standard colony diet. Animal studies were performed in compliance with the Institutional animal ethics committee of BARC. Rabbits were divided into the following 4 groups,
Group I: Control (n=2)
Group II: Intravenous exposure to 131I (1 GBq) (n=3)
Group III: Pre supplemented orally with O. Sanctum extract (40 mg/kg bwt) for 5 days and subsequent exposure to intravenous 131I (1 GBq) (n=3)
Group IV: Pre supplemented with amifostine (200 mg/kg bwt) intravenous 30 min before 131I (1 GBq) exposure (n=3)
131I was obtained from the Board of Radiation & Isotope Technology (BRIT), Vashi, India. O. sanctum extract used in the study was obtained as a generous gift from Dr. Yogendra Nayak (Department of pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal India.) Amifostine was procured from NATCO Pharma Ltd.
At three months interval, blood samples of these rabbits were taken and tested for serum SGOT, SGPT and amylase. At the end of six months interval, salivary gland scintigraphy, haemato-logical profile and above parameters were repeated, and all rabbits were sacrificed. Their salivary glands were removed, part of it was stored in 10% neutral buffered formalin and subjected to pathological and electron microscopy analysis.
Saliva Collection: Rabbits were placed in a plastic restrainer cage and injected subcutaneously with pilocarpine (0.4 mg/kg). Saliva samples collected in a glass beaker and stored at -20 ºC were processed for estimation of amylase and protein using standard protocol 19, 20.
Salivary Gland Scintigraphy: Experimental rabbits were placed in a prone position directly on the low energy high resolution (LEHR) collimator of a large field of view gamma camera ( SIEMENS signature E.CAM dual camera) After intravenous injection of 5 mCi of 99mTc pertechnetate, the image of experimental rabbits was acquired and stored in 256 × 256 matrix 21. This was done to ensure the destruction of the thyroid gland.
Haematology & Serum Biochemistry Analysis: Blood collection was done by ear vein puncture method. 2 ml of blood was collected in heparinised vacutainer for haematology parameters 22. 3 ml blood was collected in plain tube for serum SGOT and SGPT analysis (ERBA kits & IFCC method).
Histopathology: The excised parotid gland was rinsed in 0.1 M phosphate-buffered saline (0.1 M PBS) and preserved in 10% neutral buffered formalin (w/v) NBF for histology. Subsequently, the fixed tissue was rinsed, dehydrated in graded alcohol series (20%, 30%, 50%, 70%, 80%, 90%, 95% alcohol), and finally in absolute alcohol. The tissue was cleared from traces of water by immersion in xylene and embedded in molten paraffin. Blocks were trimmed of excess paraffin till the tissue was exposed 26. Tissue sections about 3-5 µ were picked up on precoated poly-L-lysine slides. Slides stained with conventional H&E stains were evaluated for pathological changes with the light microscope (Olympus B × 60).
Electron Microscopy: The excised parotid glands were trimmed into smaller pieces and immersed in ice-cold modified Karnovsky fixative for 4 h at 40 °C. After 4 h, smaller segments 2-3 mm were trimmed. These pieces were further immersed in fresh fixative and maintained at 40 °C overnight. Surplus fixative was rinsed off from the fixed segments with two washes at 15 min intervals with 0.1M cacodylate buffer at 4 °C.
Thereafter, the rinsed specimens were post-fixed with 1% osmium tetroxide (1% OsO4, w/v, Ted Pella, USA) for 60-90 min at 4 ºC. Following post-fixation, the specimens were rinsed with two washes at 15 min intervals with 0.1M cacodylate buffer at 4 °C. Thereafter they were subjected to dehydration with two washes at 15 min intervals with graded series of dry acetone beginning with 30%, 50%, 70%, 80%, 90%, 95%, and dry acetone at 4 °C. The dehydrated specimens were gradually brought to room temperature. The specimens were cleared from traces of water using two washes of toluene for 30 min each. The specimens were exposed to increasing concentrations of the embedding medium prepared in toluene for 1 h each (1 part of embedding medium + 3 parts toluene). Further, the specimens were transferred to a cocktail of two parts of embedding medium and two parts of toluene for 1 h at room temperature. Finally, the specimens were subjected to a cocktail of 3 parts of embedding medium and one part of toluene under vacuum) for 1 h at room temperature.
Ultrathin sections (60-70 nm) were cut using glass knives on an ultramicrotome (Leica Ultra cut R, Leica Microsystems, Wetzlar, Germany). Sections floated on water in the trough having silver & gold interference colours (60-75nm thickness) were picked up on 200 meshed copper grids. Sections were stained with uranyl acetate and lead citrate. Stained sections were observed under a transmission electron microscope (Tecnai G2-12, FEI, Hillsboro, United states) at an accelerating voltage of 80-100kV. Electron micrographs were captured using a Mega View III CCD (Charge Coupled Device) camera and analyzed using the analySIS™ 3.1 software provided with the TEM 24.
Statistical Analysis: Statistical significance was calculated using paired and unpaired Student’s “T” test. Statistical significance was assigned to the observations at p < 0.05.
Hematology and Biochemistry Parameters: Total Erythrocyte Count (RBC): RBC count was found to be decreased significantly in rabbits of Gr II and Gr III as compared with that of rabbits in Gr I (p=0.009, p=0.005 respectively). Whereas a significant increase in RBCs (p =0.003) was observed in rabbits of Gr IV in comparison to Gr II and comparable with Gr I Table 1.
Hemoglobin (Hb): In comparison to Gr I, all other groups have shown a reduction in the Hb levels; however, Gr-II has exhibited pronounced reduction (p=0.043). Gr IV has exhibited a slightly significant rise in Hb levels when compared with Gr-II (p =0.055) Table 1.
Platelets: Blood platelet counts remained significantly low in Gr II rabbits, compared with Gr I (p=0.003), whereas comparatively milder reductions in platelet counts were observed in Gr III and Gr IV in comparison to Gr I Table 1.
TABLE 1: EFFECT OF O.SANCTUM AND AMIFOSTINE PRE SUPPLEMENTATION ON HAEMATOLOGICAL PARAMETERS IN 131I EXPOSED GROUP (N=11)
|Parameters||Gr I||Gr II||Gr III||Gr IV|
|RBC (x103 mm3)||8.2 ± 0.2||5.6** ± 0.6||5.5** ± 0.5||9.2 ± 0.7 Δ|
|Hemoglobin (gm/dl)||14.5 ± 2.4||9.7* ± 0.8||11.1 ± 0.8||11.8 ± 1.1|
|Platelet (x103 mm3 )||600.5 ± 16.3||383.3* ± 36.7||391.3* ± 57.6||407.3 ± 10.3|
Gr I: Control, Gr II: 131I, GrIII: 131I + O.sanctum ,GrIv: 131I + Amifostine * p<0.05 , ** p<0.01 , vs Control Δ p<0.05, vs 131I
Serum Glutamic Oxaloacetic Transaminase (SGOT) & Serum Glutamic Pyruvic Transaminase (SGPT): Statistically significant increase in serum SGOT levels of Gr III as compared with Gr I (p=0.003) was noted at 3 months time interval. Whereas significant reduction in serum SGOT levels was observed in GR IV as compared with Gr I & Gr II at 3 months of the time interval. (P=0.08). No alterations in SGPT levels were observed in the rest of the animal groups. At 6 months of an interval, no major changes in serum SGOT, SGPT levels were noted Table 2.
Salivary Amylase & Protein: No appreciable differences were noted in the salivary amylase levels in the rest of the experimental groups (Gr-II, Gr-III, Gr IV) as compared to control (Gr I) Table 2.
TABLE 2: EFFECT OF RADIATION EXPOSURE ON THE LIVER ENZYMES AND SALIVARY ENZYMES IN THE EXPERIMENTAL ANIMALS (N=11)
|Group||Gr I||Gr II||Gr III||Gr IV|
Gr I: Control, GrII: 131I, Gr III: 131I + O.sanctum , Gr IV: 131I + amifostine p<0.05 *p<0.05 vs Control, ** p<0.01 ***p<0.001 Δ p<0.05 vs 131I
99mTc Pertechnetate Scintigraphy Imaging: The absence of thyroid gland was confirmed by 99mTc scintigraphy in rabbits receiving internal 131I exposure (Gr-II, Gr-III, Gr-IV). Control (Gr-I) rabbits exhibited the presence of the thyroid gland in scintigraphy study.
FIG. 1: 99M TC PERTECHNETATE UPTAKE IN EXPERIMENTAL RABBITS AT 6 MONTHS OF TIME INTERVAL
Histopathology: The hematoxylin stained tissue sections revealed appreciable cell architecture and morphology changes in rabbit parotid glands. Multiple focal areas of lipomatosis and atrophy were observed in Gr II rabbit parotid glands Fig. 2B. Gr III and Gr IV rabbits' parotid glands exhibited minimal lipomatosis and near-normal cell architecture Fig. 2C, D Table 3.
FIG. 2: HISTOPATHOLOGICAL CHANGES IN PAROTID GLAND OF THE EXPERIMENTAL RABBITS
Electron Microscopy: The electron microscopic study revealed degenerative changes in cell organelles such as the nucleus, zymogen granules, nuclear membrane, and endoplasmic reticulum in parotid glands of Gr-II rabbits Fig. 3B. as compared to Gr I Fig. 3A. However, the degenerative changes were less pronounced in Gr III and Gr IV rabbit parotid glands Fig. 3C, D. as compared to Gr-II. Amongst all, nuclear pyknosis, destruction of zymogen granules, and loss of cellular junctions are the major changes observed in Gr II rabbits as compared to Gr I; the electron microscopic study revealed degenerative changes in cell organelles such as the nucleus, zymogen granules, nuclear membrane and endoplasmic reticulum in parotid glands of Gr-II rabbits Fig. 3B. as compared to Gr I Fig. 3A. However, the degenerative changes were less pronounced in Gr III and Gr IV rabbit parotid glands Fig. 3C, D as compared to Gr-II. Amongst all, nuclear pyknosis, destruction of zymogen granules, and loss of cellular junctions are the major changes observed in Gr II rabbits as compared to Gr I Fig. 3.
FIG. 3: ELECTRON MICROSCOPIC SECTIONS OF PAROTID GLAND IN EXPERIMENTAL RABBITS
DISCUSSION: Radioprotective abilities of O. sanctum extract are well documented by Umadevi and Ganausoundari et al. in mice receiving external high dose gamma radiation exposure 13,14. We have observed radioprotection against internal 131I exposure in our earlier work using rat and mice model 17, 18. In the present study we have tried to compare the radio protective effect of O. sanctum extract with standard radioprotectant amifostine against high dose internal exposure of 131I by studying hematological profile, biochemical parameters and histopathology of the salivary gland in rabbit model. In the current experiment, a significant reduction in total erythrocyte count, platelets, and hemoglobin were seen in the rabbits exposed to a high dose (1 GBq) of 131I (Gr-II) as compared to the control group (Gr I). Transient depression in bone marrow activity leading to reduction in total blood count is observed in some of the differentiated thyroid carcinoma patients treated with 131I 1, 2. Significant increase in hemoglobin, platelets, and erythrocytes in Gr-IV and marginal raise in the same in case of Gr-III indicates encouraging effect of O. sanctum and amifostine pre supplementation on hematological profile. Radioprotective properties of amifostine and O. sanctum against external gamma radiation exposure have been reported by Ganousundari et al. on mice bone marrow cells exposed to radiation 13, 14.
The immunomodulatory property of O. sanctum is reported in the literature, indicating a beneficial effect on CBC parameters and bone marrow cells 14, 25, 26. Our observations are in agreement with these reports. Marginal incidence of hepatotoxicity due to 131I therapy is observed in the case of patients with thyroid disorders 27, 28. The absence of long-term major alterations in liver enzyme SGOT and SGPT in the current experimental group affirms the same. Salivary amylase is an important digestive enzyme secreted by salivary glands. It is often used as one marker for assessing salivary gland damage post-radiation exposure 32, 33.
In our study, salivary amylase activity remained unaltered in 131I exposed groups irrespective of their state of radio protect ant supplementation compared with the unexposed control group at 3 and 6 months duration. In literature, controversial findings are reported regarding amylase activity post 131I exposure. Chitra et al. have reported a decrease in salivary amylase and protein in patients of oral cavity carcinoma (OCC) receiving radiation therapy 29. On the contrary, Blakely et al. have reported an increase in salivary amylase activity post-radiation exposure in experimental rhesus monkey model 30. In few other studies, peaks in salivary amylase are observed, which got normalized over a period of time 31, 32. Our findings are in agreement with those observations. Salivary secretion is a result of stimulation of parotid, submandibular, lingual, and salivary glands 32. Amongst them, parotid glands are majorly functional and radiosensitive in nature. However, other glands also contribute towards salivary secretion 32. Hence, post 131I exposure through parotid glands is likely to be adversely affected; other salivary glands may contribute to the salivary output. In the present study, saliva collection was not exclusively done from the parotid gland by cannulation but was a result of stimulation of all salivary glands under pilocarpine stimulation. All these factors may be responsible for observed unaffected salivary amylase levels.
histopathological examination of the salivary gland has revealed major atrophy and lipomatosis in acinar cells of the parotid glands of the rabbits exposed to only 131I as compared to control rabbits. O. sanctum and Amifostine pre supplemented rabbits have exhibited low lipomatosis and near-normal acinar cell morphology in their parotid glands compared with 131I exposed rabbits, which agrees with the findings of Bohuslavzki et al. 21. Electron microscopy study of the parotid glands of the rabbits exposed to only 131I has exhibited nuclear pyknosis and depletion of secretory granules, whereas O. sanctum and amifostine pre supplemented rabbits have shown intact nucleus and less degenerative changes in secretory granules, cell junctions and other cell organelles Fig. 2. Kutta et al. have reported similar observations regarding the parotid gland of rabbits pretreated with 1 GBq 33. This indicates the protective effect of amifostine and O. sanctum extract pre supplementation at the cellular level in experimental rabbits.
Various strategies are planned to increase the transit time of 131I to circumvent or attenuate the salivary gland damage, which includes glandular massage after oral 131I administration, sucking lemon candy or pilocarpine stimulation to increase the salivation 6, 7. However, these are of limited utility and are also controversial in some instances. Amifostine is the only FDA-approved drug available for radioprotection of salivary glands, which has well-known side effects needing its discontinuation in adversely affected patients.
Kim et al. have reported controversial findings of cytoprotection and parenchymal radioprotection by amifostine pre-treatment in salivary glands of patients receiving 131I therapy questioning its effectiveness in clinical settings 35. As entry of 131I in salivary glands cannot be prevented due to the presence of sodium iodide symporters, the other alternative approach for radioprotection is to increase the scavenging of the reactive species generated by suitable means. In such circumstances, antioxidant pre supplementation presents an appropriate means for controlling the cell damage within the gland. O. sanctum is a potent antioxidant that is radioprotective for hematopoietic system as well as an anti-inflammatory in nature. It’s found to be nontoxic even at higher doses (2 gm/kg) and is known to have no side effects in-vivo. Our study has demonstrated a comparable radioprotective effect of O. sanctum extract pre supplementation with FDA-approved radio protect ant amifostine in rabbits. In conclusion, O. sanctum extract needs to be further tested in higher concentrations for its effect on the functional ability of the salivary gland in higher animals towards exploring its usage in clinical settings.
CONFLICTS OF INTEREST: Authors declare that there is no conflict of interest
- Iconaru L, Baleanu F and Hambye AS: Can we safely reduce the administration of 131Iodine in patients with differentiated thyroid cancer experience of the Brymann hospital in Brussels .Thyroid research 2020; 13(1):15-21.
- Nostrand VD and Freitas J: Side effects of 131I for ablation and treatment of well differentiated thyroid carcinoma thyroid cancer a comprehensive guide to clinical management. Springer 2006; 459-83.
- Hesselink ESNK, Browers AH, Jong JRD, Browers AH, Jong JRDe, Anouk NA and Horst-schrivers V: Effect of radioiodine treatment on salivary gland function in patients with differentiated thyroid carcinoma: A prospective Journal of Nuclear Medicine 2016; 57: 1685-91.
- Sunavala-Dossabhoy G: Radioactive iodine: Anunappreciated threat to salivary gland function. Oral diseases 2018; 24: 198-201.
- Jung H W, Kim JH, Jung MH,Kim SW,Jeong BK and Woo SH: Protective effect of Alpha-Lipoic acid on salivary dysfunction in a mouse model of radio iodine therapy induced sialoadenitis. International journal of molecular sciences 2020; 21: 4136.
- Jensen SB, Visinik A, Limesand KH and Reyl and ME: Salivary gland hypofunction and xerostomia in Head and Neck Radiation Patients. JNCI Monographs 2019; 53: 95-106.
- Jasmer KJ, Gilman KE, Forti KM, Weisman GA and Limesand KH: Radiation induced salivary gland dysfunction mechanisms therapeutics and future directions. Journal of Clinical Medicine 2020; 9: 4095.
- Lindegaard JC and Gratt C: Has the outlook improved for amifostine as a clinical radioprotector. Radiotherapy and Oncology 2000; 57: 113-18.
- Anne PR, Machtay M, Rosen thal DI ,Brizel DM, Morrison WH, Irwin DH, Chougule PB, Estopinal NC, Berson A and CurranWJJR MD; A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer. Int J Radiation Bio. Phys 2007; 67: 445-52.
- King M, Joseph S, Abert A, Thomas TV, Nitala MR, Woods WC, Vijaykumar S, Packianathan S: Use of amifostine for cytoprotection during radiation therapy A review. Oncology 2020; 98: 61-80.
- Dutta S, Wadekar RR and Roy T: Radioprotective natural products as alternateive complements in oncological radiotherapy. Boletín Latinoamericano Caribe de Plantas Medicinales Aromáticas 2021; 20: 101-122.
- Dowlath MJH, Karupannan SK, Sinha P, Dowlath NS, Arunachalam KD, Ravindran B, ChangSW, Nayyen-Tri and Nayyen DD: Effects of radiation and role of plants in radioprotection:a critical review. Science of The Total Environment 2021; 779.
- P Uma Devi and Ganasoundri A: Radioprotective effect of leaf extract of Indian medicinal plant Ocimum sanctum. Ind J Exp Biol 1995; 33; 205-208.
- P Uma Devi, Ganasoundri A, Rao BS and Srinivasan K: In-vivo radioprotection by Ocimum flavonoids: Survival of mice. Radiation Research 1999; 151: 74-78.
- Patel RR Tulsi: The queen of medicinal herbs. J Bioequiv Availab 2020; 12: 407-14.
- Kulkarni KV and Adavirao BV: A review on Indian traditional shrub Tulsi ( Sanctum) the unique medicinal plant. Journal of Medi Plants Studies 2018; 6: 106-110.
- Bhartiya US, Raut YS and Joseph LJ: Protective effect of Ocimum sanctum L after high-dose 131 iodine exposure in mice: an in-vivo Ind J Exp Biol 2006; 44: 647-52.
- Joseph LJ, Bhartiya US, Raut YS, Hawaldar RW, Pawar YP, Jambekar N and Rajan MGR: Radioprotective effect of sanctum and amifostine on the salivary gland of rats after therapeutic 131I exposure. Cancer Biotherapy and Radiopharmaceuticals 2011; 26: 737-43.
- Bernfield P: Enzymatic assay of alpha amylase. Methods in Enzymology 1955; 1: 149.
- Lowry OH, Rosenbrough NJ, Farr AL and Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193; 265.
- Bohuslavizki KH, Klutmann S, Brenner W, Mester J, Henze E and Clausen M: Salivary gland protection by amifostine in high –dose radioiodine treatment results of a double-blind placebo- controlled study. Journal of clinical Oncology 1998; 16: 3542-49.
- Godkar PB and Godkar PD: Text book of medical laboratory technology clinical laboratory science and molecular diagnosis. Bhalani publishing House Mumbai; 3rd Edition 2014; 1101.
- Pawar Y, Kadam D, Khandekar G and Nehte R: Gross and cytological evaluation of canine spontaneous mammary neoplasms and its correlation with histopathology and morphometric analysis. International Journal of Veterinary Science 2015; 4: 104-110.
- Thakur M, Gupta H, Singh D, Mohanti IR, Maheswari U, Vanage G and Joshi DS: Histopathological and ultra-structural effects of nanoparticles on rat testis following 90 days (Chronic study) of repeated oral administration. Journal of Nanobiotechnology 2014; 42: 1-13.
- Jeba CR, Vaidyanathan R and Rameshkumar G: Immunomodulatory activity of aqueous extract of Ocimum sanctum in rat. Int J Phar Biomed Re 2011; 2: 33-38.
- Almatroodi SA, Alsahli MA, Almatroudi A and Rahmani AH: Ocimum Sanctum: Role in disease management through modulating various biological activity. Pharmacognosy Journal 2020; 12: 1198-05
- Jhummon NP, Tohoolo B and Qu S: Iodine -131 induced hepatotoxicity in previously healthy patients with Grave’s Disease. Thyroid Research 2013; 6: 1-5.
- Quacht A, Lingyun Ji, Mishra V, Sznewajs A, Veatch J, Huberty J, Franc B, Sposto R, Groshen S, Wei D, Fitzgerald P, John M Maris, Yanik G, Hawkins RA, Judith G Villablanca and Matthay KK: Thyroid and Hepatic function after high-dose 131i-metaiodobenzylguanidine (131I-MIBG). Therapy for Neuroblastoma Pediatric blood & Cancer 2011; 56: 191-201.
- Chitra S and Shyamala D: Effect of radiation and α-tocopherol on saliva flow rate, amylase activity, total protein and electrolyte levels in oral cavity cancer. Indian J Dent Res 2008; 19: 213-18.
- Chitra S and Shyamala D: Effect of radiation and α-tocopherol on saliva flow rate, amylase activity, total protein and electrolyte levels in oral cavity cancer. Indian Journal of Dental Research 2008; 19: 213-18.
- Blakely WF, Ossetrova NI, Manglapus GL, Salter CA, Leviene IH, Jackson WE, Grace MB, Prasanna PGS, Sandgren JD and Ledney GD: Amylase and blood cell- count hematological radiation-injury biomarkersin a rhesus monkey radiation model-use of multi parameter and integrated biological dosimetry. Radiation measurements 2007; 42: 1164-70.
- Felice DF, Tombolini M, Musella A, Margarpor F, Tomboloni V and Musio D: Radiation therapy and serum salivary amylase in head and neck cancer. Oncotarget 2017; 8:
- Upadhyay A, Meng Z, Wang P, Zhang G, Jia Q, Tan J Lix, Hu T, Liu N, Zhou P, Wang S, Liu X, Wang H, Zhang C, Zhao F and Yan Z: Medicine 2017; 96(25).
- Kutta, H, Kampen U, Sagowski C, Brenner W, Bohuslavizki KH and Paulsen F: Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Strahlentherapie und Onkologie 2005; 181: 237-45.
- Grundman O, Mitchell GC and Limes KH: Sensitivity of salivary glands to radiation: from animal models to therapies. Journal of Dental Research 88: 894-903
- Kim SJ, Choi Y H, Kim I J, Jun S and Nam HY: Limited cyto protective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan. Thyroid 2008; 18: 325-31.
How to cite this article:
Bhartiya U, Pawar Y, Joseph L, Raut Y, D’souza S, Singh D, Awasare S, Nayak Y, Hawaldar R and Banerjee S: Amelioration of 131I induced salivary gland damage by ocimum sanctum and amifostine pre supplementation in rabbits. Int J Pharm Sci & Res 2022; 13(1): 206-14. doi: 10.13040/IJPSR.0975-8232.13(1). 206-14.
All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
U. Bhartiya *, Y. Pawar, L. Joseph, Y. Raut, D’ Souza S., D. Singh, S. Awasare, Y. Nayak, R. Hawaldar and S. Banerjee
Radiation Medicine Centre *, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India.
18 February 2021
15 June 2021
30 June 2021
01 January 2022