Radioprotective Effect of Ocimum sanctum and Amifostine on the Salivary Gland of Rats After Therapeutic Radioiodine Exposure

Abstract

The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine (¹³¹I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) ¹³¹I exposure. Six months duration batch received ¹³¹I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before ¹³¹I exposure separately. Increased Technetium-99m-pertechnetate (^99mTcO₄ ⁻) uptake at 30 minutes post injection in salivary glands of only ¹³¹I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only ¹³¹I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to ¹³¹I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose ¹³¹I exposure.

Introduction

High dose radioiodine (¹³¹I) therapy is a standard procedure in the treatment of differentiated thyroid cancer to ablate remnant thyroid tissue post thyroidectomy or for metastasis. Due to the presence of sodium iodide symporter, iodide gets actively transported into the thyroid gland and a number of nonthyroidal tissues such as salivary gland, stomach, lacrimal gland, and lactating mammary gland.^1,2 Among these, salivary glands are known to exhibit irreversible radiation damage such as sialadenitis, xerostomia, and neoplasia in patients with differentiated thyroid cancer after high-dose ¹³¹I therapy.^3,4 Therefore, high-dose ¹³¹I therapy is generally recommended under salivary gland stimulation in order to minimize the salivary gland damage, however, with limited success.^5,6 Ionizing radiation damages DNA either directly or indirectly via the production of free radicals. Radioprotection can be achieved by use of free radical scavengers during ¹³¹I therapy. So far, amifostine is the only chemo and radioprotective drug available to reduce the side effects of radiation exposure in patients with cancer.^7,8 Amifostine is preferentially accumulated in certain tissues including the salivary gland, thus making these tissues less sensitive to radiation damage without protecting tumor cells.^8
–10 However, a major drawback of the use of amifostine is its severe adverse effects that sometimes result in discontinuation of the use of amifostine in some patients.¹¹ However, the use of amifostine as a radioprotectant is mainly reported in patients with head and neck cancer receiving external radiation exposure.^8,11 Limited studies have reported the usage of amifostine against internal radioiodine exposure in differentiated thyroid carcinoma and with controversial results.^7,12,13

At present, many traditional ayurvedic herbal formulations, plant extracts alone or in combination, are being explored for their efficacy against radiation-induced cell damage. Among them, Ocimum sanctum, a medicinal plant in India, is known to have various beneficial effects including radioprotection against ⁶⁰Co gamma radiation.^14
–16 Our earlier work has shown better radioprotection by oral supplementation of O. sanctum as compared with other natural antioxidants in salivary glands of mice exposed to an internal therapeutic dose of ¹³¹I at 24 hours.^17
–19 Since irreversible salivary gland damage is known to occur at later stages, we thought of exploring the possible beneficial effect of O. sanctum on the salivary glands of rats after a long duration and the repeated therapeutic dose of ¹³¹I exposure and compared its efficacy with a known radioprotectant, amifostine.

Materials and Methods

Animals

Female adult Wistar rats weighing 250–300 g were obtained from Animal House Facility, BARC, Trombay, Mumbai. They were maintained in an air-conditioned room with free access to water and food. Animal studies were performed in compliance with BARC Institutional Animal Ethics Committee's guidelines.

Experimental design

Totally, 72 rats used for the experiment were divided into the following four groups with six animals each. Group I: Control. Group II: ¹³¹I exposed (18.5 MBq/100 g ¹³¹I, i.p). ¹³¹I as Na¹³¹I was obtained from the Board of Radiation and Isotope Technology. Group III: oral O. sanctum (40 mg/kg) for 5 consecutive days before 18.5 MBq/100g ¹³¹I exposure. O. sanctum used in the study was a generous gift from Dr. Yogendra Nayak, Department of Pharmacology, Manipal University, Manipal, India. Group IV: administration of amifostine (200 mg/kg, s.c.) 15 minutes before 18.5 MBq/100g ¹³¹I exposure. Amifostine was obtained from NATCO Pharma Limited. Totally, three such batches of 1, 3, and 6 months of duration receiving ¹³¹I exposure were studied.

The animals were weighed and sacrificed after 1, 3, and 6 months of duration of ¹³¹I exposure. Six-month experimental animals were exposed twice with 18.5 MBq/100g ¹³¹I with 3 months gap between the two exposures.

The experimental rats were supplemented with 1.5 μg/100 g of thyroxine (T₄) and 1% calcium lactate in drinking water to maintain the euthyroid state.

Parameters

Biodistribution studies using ^99mTc-pertechnetate

The ^99mTc-pertechnetate (^99mTcO₄ ⁻) uptake was studied by i.p. administration of 1.85 MBq of ^99mTcO₄ ⁻ to all the animals from the 1 and 6 months duration group, 30 minutes before sacrifice. ^99mTcO₄ ⁻ was prepared in-house from a ⁹⁹Molybdenum - ^99mTc generator.

The rats were sacrificed by cardiac puncture under ether anesthesia. Tissues excised for counting radioactivity included liver, stomach, kidneys, bladder, and salivary glands (parotid and submandibular from both the sides).The wet weights of the parotid and submandibular glands were recorded before measuring their ^99mTcO₄ ⁻ activity. In addition, blood was also collected and counted for its ^99mTcO₄ ⁻ activity. The percent uptake in blood was calculated by correcting it for the volume. The carcass was separately counted for its radioactive content.

The ^99mTcO₄ ⁻ activity was counted by using a broad, well-type scintillation counter designed for animal tissues, and the percent ^99mTcO₄ ⁻ uptake was calculated by considering injected activity as 100%. In case of salivary glands, the % uptake was calculated as percent injected dose/g tissue weight/kg body weight.

Histopathology

The parotid glands of 3 rats from each group at 1, 3, and 6 months of duration were fixed in 10% neutral buffered formalin. Sections at 3–5 μm were prepared and stained with hematoxylin/eosin for histopathology in a conventional manner.

Statistics

Statistical analysis was performed using ANOVA with Bonferroni correction. Within-group comparison for ^99mTcO₄ ⁻ uptake was done by using a paired t-test with a significance level <0.05, whereas between-group comparison was done by using Student's t- test with a statistical significance level <0.01(with continuity correction).

Results

Total body weight as well as parotid and submandibular weights in all the experimental rats did not show any significant change in comparison to control animals at 1, 3, and 6 months of duration (Table 1). After administration of 18.5 MBq/100g ¹³¹I, the rats from all the three groups exhibited an ablation of the thyroid gland as early as 1 month. This was evident by the absence of thyroid tissue at the time of sacrifice as well as the absence of ^99mTcO₄ ⁻uptake in the thyroid gland of these animals. Adequacy of the T₄ supplementation was observed by normalized levels of T₄ in blood samples of the experimental rats. At 1 month duration, the T₄ levels were 4.5±2.5, 3.6±1.7, 5.2±3.1, and 3.4±1.1 μg/dL in Gr. I, Gr. II, Gr. III, and Gr. IV, respectively. Similarly, at 6 months, the levels were 4.6±0.57, 5.0±1.5, 4.3±0.35, and 3.7±1.0 μg/dL in Gr. I, Gr. II, Gr. III, and Gr. IV, respectively. No toxic effects were observed in the group of rats receiving O. sanctum presupplementation, whereas 17% mortality was seen in the group of rats receiving a single s.c. injection of amifostine. However, we were not able to ascertain the exact cause of the death in amifostine-treated rats.

Table 1.

Body Weight, Parotid, and Submandibular Gland Weight of the Experimental Rats at 1, 3, and 6 Months After ¹³¹ I Exposure

	Body weight (g)			Parotid (mg)			Submandibular (mg)
Time (month)	1	3	6	1	3	6	1	3	6
Gr. I	332±32	325±30	348±31	466±62	454±103	509±63	580±39	633±141	758±90
Gr. II	326±18	295±23	307±21	432±52	364±80	520±104	537±86	480±75	556±63
Gr. III	326±13	310±22	323±22	506±114	419±92	544±54	563±38	505±42	640±59
Gr. IV	316±14	310±35	317±21	427±69	434±46	576±88	562±55	523±40	610±84

Total number of animals=72 (mean±SD).

Gr. I, control; Gr. II, ¹³¹I; Gr. III, O. sanctum+¹³¹I; Gr. IV, amifostine+¹³¹I; SD, standard deviation.

Biodistribution studies were performed using ^99mTcO₄ ⁻at 1 and 6 months of ¹³¹I exposure in two separate batches of experimental animals. The main intention of ^99mTcO₄ ⁻study was to assess the parenchymal function of the salivary glands. Figure 1 shows the percent uptake of the radioisotope in various organs after 30 minutes of ^99mTcO₄ ⁻administration in the experimental animal batch sacrificed at 1 and 6 months of duration. No significant change was observed in percent uptake in the liver, stomach, kidneys, bladder, carcass, and blood.

FIG. 1.

Biodistribution studies at 30 minutes using ^99mTcO₄ ⁻ in experimental rats (mean±standard deviation, n=6).

Table 2 shows percent ^99mTcO₄ ⁻ uptake expressed as injected ^99mTcO₄ ⁻ dose/g tissue weight/kg body weight at 30 minutes in parotid and submandibular glands from both the sides in two batches of rats sacrificed at 1 and 6 months of duration of ¹³¹I exposure. At 1 month, the percent ^99mTcO₄ ⁻ uptake in all the four groups did not demonstrate any significant alteration in parotid as well as submandibular glands. At 6 months of duration, Gr. II animals exposed to ¹³¹I exhibited an increase in ^99mTcO₄ ⁻ uptake in the parotid gland when compared with Gr. I animals at 6 months; however, the increase was not statistically significant. On the other hand, a significant increase in ^99mTcO₄ ⁻ uptake was observed in Gr. II animals at a 6 months time interval when compared with Gr. II at a 1 month interval (p=0.010). A significant elevation in ^99mTcO₄ ⁻ uptake was also observed in O. sanctum pretreated group (Gr. III) at 6 months in comparison to its 1 month counter part (p=0.039). Similarly, ^99mTcO₄ ⁻ uptake in the submandibular gland at 6 months in Gr. II animals demonstrated significant elevation in comparison to their counterpart at 1 month (p=0.015) as well as Gr. I animals at 6 months (p=0.004). In contrast, rats pretreated with O. sanctum and amifostine exhibited marked reduction in ^99mTcO₄ ⁻ uptake in the submandibular glands in comparison to Gr. II rats. The ^99mTcO₄ ⁻ uptake in Gr. III and Gr. IV rats was almost comparable to controls (Table 2). A histopathological change in the parotid gland was studied in 3 rats from each group at 1, 3, and 6 months of duration. Controls exhibited a well-defined lobular structure with densely packed acini and a well-developed duct. Parotid gland samples were purely serous. One month after ¹³¹I exposure, the parotid gland did not exhibit any significant histopathological changes in any of the experimental groups in comparison to control animals. At 3 months of duration, Gr. II rats exposed to only ¹³¹I showed progressive lipomatosis with atrophic acinar cells, whereas no significant alterations except slight vacuolization were observed in the parotid histopathology of the rats presupplemented with O. sanctum and amifostine followed by ¹³¹I exposure (Fig. 2). At 6 months with two ¹³¹I exposures, multifocal areas of lipomatosis and atrophy were observed in Gr. II animals, whereas the rats presupplemented with O. sanctum and amifostine remained comparable to controls (Fig. 3).

FIG. 2.

(A–D) Rat parotid gland histology at 3 months after ¹³¹I exposure. (A) Control parotid gland showing normal lobular structure with intact cell membrane and intact duct (original magnification 400×). (B) Parotid gland of the rat exposed to ¹³¹I exhibiting complete destruction of lobular structure and loss of parenchymal cells with progressive lipomatosis (original magnification 100×). (C) Parotid gland of the rat presupplemented with Ocimum sanctum followed by ¹³¹I exposure exhibiting well-maintained lobular structure with intact duct and presence of slight acinar vacuolization (original magnification 400×). (D) Parotid gland of the rat presupplemented with amifostine followed by ¹³¹I exposure showing normal acini with intact duct along with focal vacuolization (original magnification 400×).

FIG. 3.

(A–C) Rat parotid gland histology of the experimental animal after two ¹³¹I exposures with 3 months of gap between the two exposures. (A) Parotid gland of the rat after two ¹³¹I exposures exhibiting destroyed lobular structure with multifocal areas of lipomatosis with proliferation of fibrous connective tissue resulting in constriction of the duct (original magnification 100×). (B) Parotid gland of the rat presupplemented with O. sanctum followed by two ¹³¹I exposures exhibiting normal acini with duct (original magnification 400×). (C) Parotid gland of rat presupplemented with amifostine followed by two exposures of ¹³¹I showing normal acini with duct (original magnification 400×).

Table 2.

Percentage ^99m Tc Pertechnetate Uptake in Parotid and Submandibular Glands at 30 Minutes in Experimental Rats

	Parotid (%ID/g/kg body weight)		Submandibular (%ID/g/kg body weight)
Time (month)	1	6	1	6
Gr. I	0.645±0.14	0.657±0.48	0.539±0.07	0.579±0.30
Gr. II	0.635±0.17	1.389±0.42^a	0.633±0.27	1.219±0.30^c,d
Gr. III	0.698±0.28	1.110±0.27^b	0.618±0.24	0.834±0.30
Gr. IV	0.641±0.47	0.646±0.49	0.578±0.28	0.788±0.29

Total number of animals=72 (mean±SD).

p=0.010 vs. Gr. II (1 month).

p=0.039 vs. Gr. III (1 month).

p=0.015 vs. Gr. III (1 month).

p=0.004 vs. Gr. I (6 months).

Discussion

Salivary gland dysfunction is a known complication of ¹³¹I therapy that can have a serious impact on the quality of life of a patient with thyroid cancer.^2,20 Due to the damaging effect of ¹³¹I on the salivary gland, high-dose radioiodine therapy is generally performed under salivary gland stimulation. Sialogogues are thought to have an important function in preventing the side effects of ¹³¹I therapy.²⁰ However, this approach has its limitations, as it requires continuous administration of sialogogues.²¹ Lemon products are known to decrease the transit time of ¹³¹I through the salivary gland so as to reduce the amount of radiation exposure to the tissues, however, without much beneficial effect in the patient population.^5,6 In view of good prognosis of differentiated thyroid carcinoma after ¹³¹I therapy, it is important to avoid the salivary gland damage, ultimately improving the quality of life of these patients. Currently, amifostine is the only drug approved by the Food and Drug Administration for the purpose of radioprotection in patients with cancer. However, it is known to exhibit adverse effects that may lead to the discontinuation of the same in some patients.^11,22 In addition, its beneficial effects in patients with thyroid cancer undergoing ¹³¹I therapy are yet to be established.^12,13 Hence, the major focus of our experiment was to develop a better radioprotectant for the salivary gland against therapeutic ¹³¹I exposure that would be nontoxic and highly effective. Our earlier work in mice had given us encouraging preliminary results for salivary gland radioprotection against 3.7 MBq of ¹³¹I exposure for 24 hours by using O. sanctum presupplementation.^17,19

Our current experiment compares the effect of O. sanctum and amifostine presupplementation on the body weight and salivary gland weight of the rats. Biodistribution of ^99mTcO₄ ⁻after 30 minutes of administration was compared in various organs including salivary glands. No significant change in the body weight and salivary gland weight was observed at 1, 3, and 6 months after radioiodine exposure. Nagler et al. have observed significant reduction in body weights as well as salivary gland weight after ⁶⁰Co external radiation exposure of 10 and 15 Gy at 3, 6, 9, and 12 months time interval.^23,24 However, our experimental design was different, where the animals were exposed to a single internal therapeutic dose of ¹³¹I of 18.5 MBq.

The batch of experimental animals sacrificed at 6 months time interval receiving two ¹³¹I exposures showed 2.19 and 1.59 times increase in ^99mTcO₄ ⁻ uptake within groups in the parotid gland of Gr. I, Gr. III animals. However, in the submandibular gland, the increase was 1.92, 1.35 and 1.36 times in Gr. II, Gr. III, and Gr. IV, respectively, when compared with 1 month exposure. The observed increase was statistically significant in ¹³¹I exposed group in parotid as well as submandibular glands. O. sanctum pretreated and ¹³¹I exposed group also demonstrated a significant increase in ^99mTcO₄ ⁻ uptake in parotid glands. Trapping of ^99mTcO₄ ⁻ by the salivary gland generally begins at 1 minute and reaches a peak in about 5–10 minutes. At a later stage, it also provides the information regarding the excretion pattern. The observed increase in the uptake could be the indication of slow excretion due to the parenchymal damage, thus resulting in delayed ^99mTcO₄ ⁻ clearance ultimately increasing ^99mTcO₄ ⁻ uptake. In contrast, Bohuslavizki et al.²⁵ have observed progressive decline in ^99mTcO₄ ⁻ uptake from 4 to 24 weeks after 2 GBq of ¹³¹I exposure by acquiring sequential images of each up to 25 minutes in the same batch of animals. However, we have studied the percent uptake of ^99mTcO₄ ⁻ at 30 minutes of fixed time interval in parotid and submandibular glands of the experimental rats. We could not perform the sequential imaging in the same batch of animals, as they were sacrificed at fixed time intervals. Detailed sequential imaging studies in these groups particularly in O. sanctum pretreated (Gr. III) and amifostine (Gr. IV) pretreated groups are required to address the reason for the difference in clearance of the ^99mTcO₄ ⁻ in the salivary glands in these two groups.

The histopathological studies have shown no significant changes in parotid gland architecture at 1 month. The lack of significant morphological alteration at 1 month is in agreement with many earlier reports.^{26− 29} Our study differs from those with regard to the type of radiation used. They have externally irradiated the head and neck region of the experimental animals with ⁶⁰Co, whereas in the present experiment, the rats were exposed to ¹³¹I in vivo. At later stages such as 3 and 6 months of duration, ¹³¹I exposed rats show cellular atrophy in the parotid gland accompanied by lipomatosis. On the other hand, rats pretreated with O. sanctum and amifostine showed comparable cellular histology to control animals. This is in agreement with the observation reported by Bohuslavizki et al.,²⁵ wherein rabbits were exposed to a high dose of ¹³¹I in vivo to study the radioprotective effect of amifostine. Kutta et al.³⁰ studied the radioprotective effect of amifostine on the histology as well as electron microscopy of the salivary gland of rabbits after exposure to ¹³¹I. They have observed marked lipomatosis and apoptosis in the salivary gland of the rabbits exposed to 1 GBq radioiodine exposure at 3 and 6 months of duration. Similarly, Yan et al. have also observed severe salivary gland damage after external duel field irradiation at 16 weeks of time interval in the pig parotid gland in comparison to a single-field irradiation of the same dose.³¹

The radioprotective effect of amifostine is attributed to its preferential localization in the salivary glands and ability to scavenge free radicals.¹¹ In the current study, the beneficial effect of amifostine was observed on the glandular histology of rats receiving ¹³¹I exposure as well as uptake studies done at 30 minutes after administration of ^99mTcO₄ ⁻. This indicates the radioprotective ability of the amifostine against internal ¹³¹I exposure in salivary glands. Nonetheless, the adverse side effects, limited route of administration, narrow time window, cost, and need of medical supervision has limited its use in patient population.^8,22 In this context, we have observed 17% mortality in amifostine-treated group, whereas no such adverse effect was found in the group presupplemented with O. sanctum, which is easily available and a cost-effective natural antioxidant. In addition, O. sanctum presupplementation also exhibits beneficial effects on the histopathology of the salivary gland, thus indicating radioprotective ability against ¹³¹I exposure.

In case of differentiated thyroid carcinoma, the usage of amifostine as a radioprotectant has not been unequivocally accepted. Controversial reports regarding its efficacy underline the need of exploring a better radioprotectant for the salivary gland protection after high-dose ¹³¹I therapy. In the light of this, our study reports the radioprotective ability of O. sanctum on the salivary gland in rats exposed to ¹³¹I. The use of O. sanctum should be explored in detail for its effect on the functional ability of the salivary gland as a safe radioprotectant that can be effectively used in patients with differentiated thyroid carcinoma receiving ¹³¹I therapy.

Footnotes

Disclosure Statement

The authors declare that there are no financial or other conflicting interests in the present work.

References

Solans

, Bosch

, Galofre

et al. Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J Nucl Med, 2001; 42:738.

Chow

. Side effects of high-dose radioactive iodine for ablation or treatment of differentiated thyroid carcinoma. J Hong Kong College Radiol, 2005; 8:127.

Alexander

, Bader

, Schaefer

et al. Intermediate and long- term side effects of high- dose radioiodine therapy for thyroid carcinoma. J Nucl Med, 1998; 39:1551.

Mendoza

, Shaffer

, Karakla

et al. Quality of life with well-differentiated thyroid cancer: Treatment toxicities and their reduction. Thyroid, 2004; 14:133.

Bohuslavizki

, Brenner

, Lassmann

et al. Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine. Nucl Med Commun, 1996; 17:681.

Nakada

, Ishibashi

, Hirata

et al. Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer. J Nucl Med, 2005; 46:261.

Bohuslavizki

, Brenner

, Klutmann

et al. Radioprotection of salivary glands by amifostine in high-dose radioiodine therapy. J Nucl Med, 1998; 39:1237.

Weiss

, Landauer

. History and development of radiation-protective agents. Int J Radiat Biol, 2009; 85:539.

Yuhas

, Spellman

, Culo

. The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin Trials, 1980; 3:211.

10.

Wasserman

, Phillips

, Ross

et al. Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by WR-2721. Cancer Clin Trials, 1981; 4:3.

11.

Jensen

, Pedersen

, Vissink

et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Management strategies and economic impact. Support Care Cancer, 2010; 18:1061.

12.

Kim

, Choi

, Kim

et al. Limited cytoprotective effects of amifostine in high-dose radioactive iodine −131 treated well-differentiated thyroid cancer patients: Analysis of quantitative salivary scan. Thyroid, 2008; 18:325.

13.

, Xie

, Chen

et al. Amifostine for salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer. Cochrane Database Syst Rev, 2009; 7:CD007956.

14.

Uma Devi

, Ganasoundri

. Radioprotective effect of leaf extract of Indian medicinal plant Ocimum sanctum. Ind J Exp Biol, 1995; 33:205.

15.

Uma Devi

, Ganasoundri

, Rao

BSS

et al. In-vivo radioprotection by Ocimum flavonoids: Survival of mice. Rad Res, 1999; 151:74.

16.

Uma Devi

, Ganasoundari

, Vrinda

et al. Radiation protection by the Ocimum flavonoids Orientin and Vicenin: Mechanism of action. Rad Res, 2000; 154:455.

17.

Bhartiya

, Raut

, Joseph

et al. Protective effect of Ocimum sanctum L after high-dose 131 iodine exposure in mice. Ind J Exp Biol, 2006; 44:647.

18.

Bhartiya

, Raut

, Joseph

et al. Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine. Ind J Clin Biochem, 2008; 23:382.

19.

Bhartiya

, Joseph

, Raut

et al. Effect of Ocimum sanctum, turmeric extract and vitamin E supplementation on the salivary gland and bone marrow of radioiodine exposed mice. Ind J Exp Biol, 2010; 48:566.

20.

Jensen

, Pedersen

AML

, Vissink

et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Prevalence, severity and impact on quality of life. Support Care Cancer, 2010; 18:1039.

21.

Greenspan

, Daniels

. Effectiveness of pilocarpine in postradiation xerostomia. Cancer, 1987; 59:1123.

22.

Hosseinimehr

. Foundation review: Trends in the development of radioprotective agents. Drug Discovery Today, 2007; 12:794.

23.

Nagler

, Baum

, Miller

et al. Long-term salivary effects of single dose head and neck irradiation in the rat. Arch Oral Biol, 1998; 43:297.

24.

Nagler

. Extended-term effects of head and neck irradiation in a rodent. Eur J Cancer, 2001; 37:1938.

25.

Bohuslavizki

, Klutmann

, Jenicke

et al. Radioprotection of salivary glands by S-2-(3-Aminopropylamino)-ethylphorothioic (Amifostine) obtained in a rabbit animal model. Int J Radiat Oncol Biol Physics, 1999; 45:181.

26.

Paardekooper

, Cammelli

, Zeilstra

et al. 1998. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function. Int J Radiat Biol, 1998; 73:641.

27.

O'Connell

, Redman

, Evans

et al. Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling. Rad Res, 1999; 151:150.

28.

Zeilstra

, Vissink

, Konings

et al. Radiation induced cell loss in rat submandibular gland and its relation to gland function. Int J Radiat Biol, 2000; 76:419.

29.

Vitolo

, Cotrim

, Sowers

et al. The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. Clin Cancer Res, 2004; 10:1807.

30.

Kutta

, Kampen

, Sagowski

et al. Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Strahlenther Onkol, 2005; 181:237.

31.

Yan

, Hai

, Shan

et al. Effect of same-dose single or dual field irradiation on damage to miniature pig parotid glands. Int J Oral Sci, 2009; 1:16.

Radioprotective Effect of Ocimum sanctum and Amifostine on the Salivary Gland of Rats After Therapeutic Radioiodine Exposure

Abstract

Introduction

Materials and Methods

Animals

Experimental design

Parameters

Biodistribution studies using 99mTc-pertechnetate

Histopathology

Statistics

Results

Discussion

Footnotes

Disclosure Statement

References

Biodistribution studies using ^99mTc-pertechnetate