The effect of early and long-term propranolol therapy on learning and memory in mice.

Propranolol is the treatment of choice for infantile hemangioma. We investigated the effects of long-term propranolol use in early infancy on learning and memory later in life in mice. At three weeks of age, mice were randomly divided into six experimental groups. Groups 1 and 2 (controls) received only saline for 21 days. Groups 3 and 4 received propranolol (2.5 mg/kg) for 21 days. Groups 5 and 6 received propranolol (5 mg/kg) for 21 days. Groups 1, 3 and 5 were tested at the end of 21 days of treatment (week 6). However, groups 2, 4 and 6 received a 2-week break and then (week 8) exposed to tests. In the Morris water maze test, propranolol (2.5 and 5 mg/kg) dose-dependently increased the time spent in the target quadrant in mice at weeks 6 and 8. However, propranolol did not affect the swimming speed in both time periods. There were no significant effects of propranolol on the number of errors evaluated during the radial arm maze tests. In conclusion, long-term use of propranolol in early infancy did not disrupt the learning and memory of mice.

Silibinin Effect on Methotrexate-Induced Hepatotoxicity in Rats.

OBJECTIVE: Hepatotoxicity is one of the major side effects of methotrexate and limits its use. In this study, we investigated the hepatoprotective effect of silibinin and the role of oxidative stress markers and cytokines on high-dose methotrexate-induced hepatotoxicity in rats. MATERIALS AND METHODS: In this study, rats were randomly divided into 5 groups (n=7). Methotrexate (20 mg/kg, intraperitoneally) was administered on the first day in all groups except control. Silibinin was injected for 5 days to methotrexate-silibinin25, methotrexate-silibinin50, and methotrexate-silibinin100 groups at a dose of 25, 50, and 100 mg/kg/day, respectively. On the sixth day, blood and liver samples were obtained and rats were sacrificed. Serum total antioxidant capacity, total oxidant status, total thiol, native thiol, alanine aminotransferase, aspartate transaminase, bilirubin, albumin, tumor necrosis factor-alpha, and interleukin-10 levels were measured. In addition, a histopathological evaluation of liver tissues was performed. RESULTS: Methotrexate reduced total antioxidant capacity and increased disulfide/total thiol ratio. Histopathologic examination revealed that methotrexate increased hepatic damage and 50 mg/kg/dose of silibinin prevented inflammatory cell infiltration in particular. CONCLUSION: Our results suggest that silibinin (50 mg/kg/day) may reduce the hepatic damage in methotrexate-induced hepatotoxicity in rats by increasing antioxidant capacity.

Effects of long-term treatment with haloperidol, clozapine and aripiprazole on mice isolated vas deferens.

PURPOSE: Sexual dysfunction is a common condition in patients taking antipsychotics and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. Pharmacology research into human ejeculatory disorders is limited to clinical studies with registered drugs affecting the ejaculation process; therefore, animal research has become the need. We aimed to investigate the effects of haloperidol, clozapine and aripiprazole on serotonin, noradrenaline, adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in order to evaluate the effect of haloperidol, clozapine and aripiprazole on the contraction of the vas deferens. METHODS: Male inbred BALB/c ByJ mice aged 7 weeks upon arrival to the laboratory were used in this study. Haloperidol, clozapine, aripiprazole, serotonin, noradrenaline, ATP and KCl were dissolved in 0.9% physiological saline. The mice were randomly divided into experimental groups as follows: saline; haloperidol 0.125 mg/kg; haloperidol 0.25 mg/kg; clozapine 1.25 mg/kg; clozapine 2.5 mg/kg; aripiprazole 3 mg/kg; aripiprazole 6 mg/kg. Mice were treated by ip injection of drugs during 21 days. Mice receiving only the vehicle ip (0.9% saline) during 21 days served as control group (n = 7). Each experimental group consisted of 7 mice. After 21 days of treatment, epididymal and prostatic portions of vas deferens were surgically dissected free and immersed in 20-mL organ baths containing Krebs' solution. The effects of chronic treatment with haloperidol (0.125 and 0.25 mg/kg), clozapine(1.25 and 2.5 mg/kg) and aripiprazole (3 and 6 mg/kg) were investigated on serotonin [10 (-8) to 10 (-4) M], noradrenaline [10 (-8) to 10 (-4) M], ATP [10 (-8) to 10 (-4) M] and 80 mM KCl-induced contractile responses in the epididymal and prostatic portions of mice isolated vas deferens strips. Statistical comparison between the groups was performed using ANOVA supported by Dunnett's post hoc test. RESULTS: Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portions of the vas deferens obtained from the haloperidol-treated group and clozapine-treated group. However, aripiprazole treatment had no effect on serotonin responses in both epididymal and prostatic portions of mice vas deferens. On the other hand, haloperidol and clozapine treatments significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens, but had no effect on KCl-induced contractions of the vas deferens in both portions. There were no significant differences in KCl-induced contractile responses among the groups. CONCLUSIONS: These results revealed that induced contractions of vas deferens were affected after chronic treatment with haloperidol and clozapine but not aripiprazole. Serotonergic, noradrenergic and purinergic receptors may, at least in part, contribute to changes in vas deferens contractions in mice with chronic treatment of haloperidol and clozapine but not aripiprazole.

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna.

PURPOSE: Hemorrhagic cystitis (HC) is the most common urotoxic side effect of cyclophosphamide (CP). The aim of this study was to compare the classical efficacy of mesna (2-mercaptoethane sulfonate sodium) with three different doses of resveratrol (RES) on cyclophosphamide-induced HC in rats. METHODS: Forty-six male Sprague-Dawley rats were divided into six groups. Group 1 served as a negative control (sham). Five groups received a single dose of cyclophosphamide (150 mg/kg) intraperitoneally at the same time. Groups 2, 3, 4, 5, and 6 received only CP, CP + 20 mg/kg RES, CP + 40 mg/kg RES, CP + 80 mg/kg RES, and CP + classical protocol of three doses of mesna (30 mg/kg three times), respectively. Antioxidants, cytokines, and malondialdehyde levels were measured in all groups. In addition, histopathological alterations in tissues were examined. RESULTS: CP administration induced severe HC with marked edema, hemorrhage, and inflammation in group 2. RES 20 mg/kg showed meaningful protection against bladder damage compared to the control group. It was seen that RES 40 mg/kg gave weaker protection but RES 80 mg/kg was not found to be effective. CONCLUSION: In conclusion, marked bladder protection was found in 20 and 40 mg/kg RES applications compared to the control group, but this protection was weaker than with mesna.

Royal jelly can diminish secondary neuronal damage after experimental spinal cord injury in rabbits.

The aim of this experimental study was to investigate the neuroprotective effect of Royal jelly (RJ) on traumatic spinal cord injury (SCI). Twenty-one New Zealand male rabbits, weighing between 2.5 and 3.0 kg were divided into three groups: Sham (no drug or operation, n = 7), Control (laminectomy+single dose of 1 ml/kg saline orally, after trauma; n = 7) and RJ (laminectomy+100mg/kg RJ, orally, after trauma, n = 7). Laminectomy was perfor med at T10 and balloon catheter was applied extradurally for traumatic SCI. Four and 24h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. Four hours after SCI, all animals in control or RJ treated groups became paraparesic. Significant improvement was observed in RJ treated group, 24h after SCI, with respect to control. Traumatic SCI led to increase in the lipid peroxidation and decrease enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. RJ treatment mostly prevented lipid peroxidation and also augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, RJ treatment significantly decreased the apoptotic cell number induced by SCI.

Serum and liver tissue bio-element levels, and antioxidant enzyme activities in carbon tetrachloride-induced hepatotoxicity: protective effects of royal jelly.

The liver is a vital organ, and its function is generally impaired by chemicals. Some natural compounds have a protective role against liver diseases such as royal jelly (RJ). To our knowledge, there are no data available on the effect of RJ therapy on the levels of bio-element metabolisms and antioxidant enzyme activities in the carbon tetrachloride (CCl(4))-induced liver damage. Therefore, in the present study, we have investigated the role of RJ therapy in the trace and major elements and antioxidant enzymes in CCl(4)-induced hepatotoxicity in rats. Antioxidant enzyme activities decreased in the CCl(4)-treated group more than they did in the sham and RJ-administered groups. Many bio-element levels were also reduced in only the CCl(4)-treated group. This showed that the depletion of trace elements was related to erythrocyte antioxidant enzyme activities. RJ administration clearly increased the trace and major element levels and antioxidant enzyme activities in RJ groups. RJ may be used as functional foods because of their naturally high antioxidant potential and rich element content.

The roles of melatonin and vitamin E plus selenium in prevention of oxidative stress induced by naloxone-precipitated withdrawal in heroin-addicted rats.

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Antioxidant enzyme and element status in heroin addiction or heroin withdrawal in rats: effect of melatonin and vitamin E plus Se.

Heroin use, withdrawal syndrome, and heroin-related deaths are still the most serious public health problems. Antioxidants and bio-elements are essential for metabolism in living organisms. To our knowledge, there are no data about the effect of antioxidant therapy on the levels of bio-elements and antioxidant enzymes in the naloxone (NX)-induced heroin withdrawal syndrome. Therefore, in the present study for the first time, we have investigated the role of antioxidant therapy, melatonin, and vitamin E plus Se, on the trace and major elements and antioxidant enzymes in the heroin addiction or heroin withdrawal in rats. Glutathione peroxidase levels were increased and catalase levels were decreased in the all study groups when compared to the sham group. The level of superoxide dismutase (SOD) in the fixed dose of heroin (FDH) given group was lower; however, in the variable doses of heroin (VDH) given group SOD level was higher. Furthermore, in withdrawal syndrome, Fe, Mg, Mn, and Ti levels were diminished and Al, Ca, and Cu levels were increased in the FDH+NX group. Moreover, Mg, Mn, and Se levels were also diminished and Al level was increased in the VDH+NX group. In conclusion, our results obviously indicated that heroin effected both bio-element status and antioxidant enzyme activities and, exogenous melatonin or vE+Se therapy might relieve on the element and antioxidant enzyme the destructive activity caused by heroin.

Protective potential of Royal Jelly against carbon tetrachloride induced-toxicity and changes in the serum sialic acid levels.

Royal Jelly (RJ) is used in the Turkish folk medicine for the treatment of number of disorders. The present study describes the hepatoprotective and antioxidant activities of the RJ against carbon tetrachloride (CCl(4))-induced acute liver damage. Sprague-Dawley rats were used for the experiment. CCl(4) (0.8 ml/kg; s.c.) and RJ (50, 100, 200mg/kg; orally) were given every other day, for 20 days. Malondialdehyde, reduced glutathione in whole blood and tissues; ceruloplasmin, sialic acid, ascorbic acid, retinol, ß-carotene and liver enzymes levels in serum were measured. Additionally, histopathological alterations in the liver were examined. RJ exerted the significant protective effect on liver damage as well as on oxidative stress induced by CCl(4), resulting in reduced lipid peroxidation and improved endogenous antioxidant defence systems. It also reduced the elevated levels of liver enzymes. Histopathological study further confirmed the hepatoprotective effect of RJ, when compared with the CCl(4) treated control groups. In conclusion, present study reveals biological evidence that supports the use of RJ in the treatment of chemical-induced hepatotoxicity.

Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

Dantrolene can reduce secondary damage after spinal cord injury.

The aim of this experimental study was to investigate the possible protective effects of dantrolene on traumatic spinal cord injury (SCI). Twenty-four New Zealand rabbits were divided into three groups: Sham (no drug or operation, n = 8), Control (SCI + 1 mL saline intraperitoneally (i.p.), n = 8), and DNT (SCI + 10 mg/kg dantrolene in 1 mL, i.p., n = 8). Laminectomy was performed at T10 and balloon catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. After 4 h SCI, all animals in control or DNT-treated groups became paraparesic. Significant improvement was observed in DNT-treated group, 24 h after SCI, with respect to control. Traumatic SCI led to an increase in the lipid peroxidation and a decrease in enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. DNT treatment prevented lipid peroxidation and augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, DNT treatment significantly decreased the apoptotic cell number induced by SCI. In conclusion, experimental results observed in this study suggest that treatment with dantrolene possess potential benefits for traumatic SCI.

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study.

The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twenty-two New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI + single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI + 1 microg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI.

Antioxidative role of melatonin in organophosphate toxicity in rats.

Previous studies revealed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compound toxicity. The aim of the present study was to investigate both prophylactic and therapeutic effects of melatonin against fenthion-induced oxidative stress in rats. Therefore, we determined the changes in the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the whole blood, brain, pectoral muscle, liver, lung, heart, kidney, pancreas, and jejunum. Also, the changes in the levels of serum nitrite and nitrate, ascorbic acid, retinal, b-carotene, and ceruloplasmin were measured. In addition, activities of enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in erythrocyte of normal and experimental animals were measured. It was found that fenthion administration increased the levels of MDA in all tissues and decreased or increased the levels of GSH in some tissues. In comparison to nitrate, nitrite and ascorbic acid levels in the serum of experimental groups, there was no significant difference between groups. However, fenthion toxicity led to decrease in retinol and beta-carotene levels; melatonin administration significantly prevented this decrease. Serum ceruloplasmin level was increased due to fenthion administration, but prophylactic and therapeutic melatonin administration inhibited the increase in ceruloplasmin level of serum. There was no significant change in SOD levels in melatonin-administered groups. Melatonin modulates the fenthion-induced changes in the activities of GPx and CAT. In conclusion, the results of the current study revealed that OP toxicity, induced by fenthion, activated oxidant systems in all antioxidant systems in some tissues. Melatonin administration led to a marked increase in antioxidant activity and inhibited lipid peroxidation in most of tissues.

Beneficial effect of N-acetylcysteine against organophosphate toxicity in mice.

Recent studies showed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compounds toxicity. The aim of present study was to investigate either prophylactic and therapeutic effects of N-acetylcysteine (NAC) against fenthion-induced oxidative stress in mice. Additionally, the effects on survival rates were investigated. Therefore, we determined the changes of the blood levels of glutathione (GSH), malondialdehyde (MDA), nitrite, and nitrate in blood or serum. Additionally, all animals were observed for 6 h and the survival rates were recorded. It was found that fenthion administration increased the levels of MDA, and decreased the levels of GSH, nitrite and nitrate. On the other hand, both prophylactic and therapeutic NAC treatment decreased the levels of MDA, and increased the levels of GSH, nitrite, and nitrate. The results showed that NAC is able to attenuate the fenthion-induced oxidative stress whereby NAC has not only prophylactic but also therapeutic activity in fenthion poisoning. On the other hand, we found that NAC can clearly improve survival rates in mice administered with an acute high dose of fenthion poisoning. In conclusion, NAC can decrease OP-induced oxidative stress and mortality rate, but the exact mechanism of its NAC protective effect needs to be explored further.

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats.

AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs 13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Melatonin protects rat liver against irradiation-induced oxidative injury.

The aim of this study was to investigate the antioxidant roles of different doses of melatonin (5 and 10 mg x kg (-1) ) against gamma-irradiation-caused oxidative damage in liver tissue after total body irradiation (TBI) with a single dose of 6.0 Gy. Fifty adult rats were divided into 5 equal groups, 10 rats each. Groups I and II were injected with 5 and 10 mg x kg (-1) of melatonin, and group III was injected with an isotonic NaCl solution. Group IV was injected with only 5 mg x kg (-1) of melatonin. Group V was reserved as a sham control. Following a 30-min-period, 6.0 Gy TBI was given to groups 1, 2 and 3 in a single fraction. The liver malondialdehyde (MDA) levels, super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured in all groups. TBI resulted in a significant increase in the liver tissue MDA levels and a decrease of SOD and GSH-Px activities. The results demonstrated that the liver tissue MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg x kg (-1) ) were significantly decreased, while the SOD and GSH-Px activities were significantly increased. Decreasing the MDA levels by melatonin was dose dependent, but the liver tissue SOD and GSH activities were not. The data obtained in this study suggest that melatonin administration prior to irradiation may prevent liver damage by irradiation.

Melatonin reduces lipid peroxidation and nitric oxide during irradiation-induced oxidative injury in the rat liver.

Radiation therapy is a popular and useful tool in the treatment of cancer. Melatonin participates in the regulation of a number of important physiological and pathological processes. Melatonin, a powerful endogenous antioxidant, plays a role in the reduction of oxidative damage. Thirty adult rats were divided into five equal groups. On the day of the experiment, groups I and II were injected with 5 or 10 mg/kg melatonin, respectively, while group III received isotonic NaCl solution. Thirty minutes later, groups I, II and III were exposed to 6.0 Gy whole body ionizing radiation in a single fraction. Group IV was injected with 5 mg/kg melatonin but was not irradiated. The final group was reserved as sham treated. Liver malondialdehyde (MDA) and nitric oxide (NO*) levels were measured in all groups. Whole body irradiation caused a significant increase in liver MDA and NO* levels. Hepatic MDA and NO* levels in irradiated rats that were pretreated with melatonin (5 or 10 mg/kg) were significantly decreased. Malondialdehyde and NO* levels were reduced in a dose-related manner by melatonin. The data show that melatonin reduces liver damage inflicted by irradiation when given prior to the exposure to ionizing radiation. The radioprotective effect of melatonin is likely achieved by its ability to function as a scavenger for free radicals generated by ionizing radiation.

Anti-inflammatory and antinociceptive properties of dantrolene sodium in rats and mice.

Our study aimed at examining the possible anti-inflammatory and antinociceptive effects of dantrolene sodium in rats and mice. The anti-inflammatory effect of dantrolene sodium (2.5, 5 and 10 mg kg (-1)) was investigated and compared with diclofenac sodium (5 mg kg (-1)) using the formalin-, histamine-, and carrageenan-induced paw oedema and cotton pellet granuloma tests. Analgesic effects of dantrolene sodium were evaluated and compared with metamizol (200 mg kg (-1)) in acetic acid-induced writhing and formalin-induced paw licking tests. It was found that dantrolene sodium significantly diminished the nociceptive response in mice, showing at the same time considerable anti-inflammatory properties in rats.

The effect of melatonin on peripheral blood cells during total body irradiation in rats.

Melatonin, has been reported to participate in the regulation of a number of important physiological and pathological process. It has also the ability to protect the genetic material of hematopoietic cells of mice from damaging effects of acute total body irradiation. The objective of this study was to the potential radioprotective effects of pharmacological doses of melatonin in total body irradiated rat's peripheral blood cells. Forty adult rats were divided into 4 equal groups. Group 1 received no melatonin or irradiation (control group), while group 2 received only melatonin (5 mg/kg, i.p.). Group 3 received only total body irradiation (RT) by 5 Gy of gamma irradiation only and group 4 received RT plus melatonin (5 mg/kg, i.p., 30 min before RT). An hour and a half following RT, blood samples were taken. Leukocytes and thrombocytes number and hemoglobin levels were measured in all groups. Five mg/kg dose of melatonin significantly protected leukocytes and as well as thrombocytes number against y irradiation. There were no significant differences between Hb levels. Our results suggest that melatonin administration prior to irradiation prevented radiation damage on peripheral blood cells. Melatonin radioprotection is achieved by its ability as a scavenger for free radicals generated by ionizing radiation and acts probably as a growth factor, especially for granulocytes in bone marrow.