Therapeutic effects of cinnamon bark oil on sciatic nerve injury in rats.

OBJECTIVE: The aim of this study was to investigate the effects of cinnamon bark essential oil (CBO) on analgesia, motor activity, balance, and coordination in rats with sciatic nerve damage. MATERIALS AND METHODS: Rats were divided into three groups as simply randomized. The right sciatic nerve (RSN) of the Sham group was explored. Only vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury (SNI) group was explored. Damage was created by unilateral clamping, and vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury+cinnamon bark essential oil (SNI+CBO) group was explored. SNI was created by unilateral clamping and CBO was applied for 28 days. In the experiment study, motor activity, balance, and coordination measurements were made with rotarod and accelerod tests. A hot plate test was performed for analgesia measurements. Histopathology studies were carried out with the sciatic nerve tissues. RESULTS: In the rotarod test, there was a statistically significant difference between the SNI group and the SNI+CBO group (p<0.05). According to the accelerod test findings, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups. In the hot plate test, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups (p<0.05). In comparison to the Sham group and the SNI group, the SNI+CBO group was shown to have the greatest expression level of vimentin. CONCLUSIONS: We have concluded that CBO can be used as an adjuvant treatment in cases of SNI, increased pain, nociception, impaired balance, motor activity, and coordination. Our results will be supported by further studies.

Effects of agomelatine on rat liver regeneration following partial hepatectomy.

Primary or metastatic hepatic malignancies are common. Partial hepatectomy (PH) is the primary treatment for both benign and malignant hepatic neoplasms; it also is used for living donor liver transplantation. The regenerative potential of the liver after PH is 70-80% in humans. We investigated the protective and therapeutic effects of agomelatine (AGM) on rat liver regeneration following PH. We used 32 rats distributed equally into four groups: group 1, sham control; group 2, PH group; group 3, administered 20 mg/kg AGM orally once/day for 7 days following PH; group 4, administered 20 mg/kg AGM orally once/day 3 days before and 7 days following PH for 10 days. Liver samples were analyzed for antioxidants and free radicals. Tissue samples were processed and stained with hematoxylin and eosin to assess histopathological status and stained immunohistochemically for Ki-67. We found that PH reduced antioxidant enzymes and increased tissue reactive oxygen species, whereas AGM treatment had the opposite effect on these parameters. Our biochemical and histopathological findings were consistent. PH caused sinusoid congestion and dilation. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas these were reduced in group 4. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas it was reduced in the group 4 compared to group 1. We found that AGM was hepatoprotective following PH due to its antioxidant and free radical scavenger properties.

Protective effect of short-term thymoquinone administration on the central nervous system in cisplatin-induced neurotoxicity.

OBJECTIVE: This study was performed to investigate the potential beneficial effects of thymoquinone (TQ) on brain tissue based on biochemical and histopathological analyses in cisplatin (CIS) treated rats with central nervous system (CNS) neurotoxicity. MATERIALS AND METHODS: The rats were randomly divided into 4 groups with 8 rats in each group (n:8). Group 1: (Control), saline was administered for 3 days at a volume of 0.5 ml per day intraperitoneal (i.p.). Group 2: (CIS Group), one dose of CIS was administered (7 mg/kg i.p.). Group 3: (TQ Group), TQ was given at a dose of 5 mg/kg per day for 3 days (i.p.). Group 4: (CIS+TQ Group), one dose of 7 mg/kg was initiated half an hour before administration of CIS and one dose of 5 mg/kg per day was administered TQ i.p. for 3 days. RESULTS: Malondialdehyde levels were found to be statistically significantly higher in the CIS group compared to the control group. Degenerative changes observed in the CIS+TQ group were found to be milder than in the CIS group. In the CIS+TQ group, a statistically significant decrease in the severity of caspase-3 immunoreactivity was found when compared to the CIS group. It was found that the severity of neurofilament immunoreactivity monitored in neuronal extensions was similar in all groups. In the CIS+TQ group, the severity of tau protein's immunoreactivity was similar to that of the CIS-group. CONCLUSIONS: According to the results obtained in our study, beneficial effects were obtained in reducing neurotoxicity with short-term TQ application in rats treated with CIS treatment.

Melatonin: A review of its potential functions and effects on neurological diseases.

BACKGROUND: The aging process is not univocal, both body and brain age. Neurological disorders are a major cause of disability and death worldwide. According to the Global Burden of Disease Study 2015, neurological diseases are the second most common cause of death and 16.8% of total deaths are caused by neurological diseases worldwide. Neurological disease deaths have risen 36% worldwide in 25 years. Melatonin is a neuroregulator hormone that has free radical scavenger, strong antioxidant, anti-inflammatory, and immunosuppressive actions. These major properties of melatonin can play an important role in the pathophysiological mechanisms of neurological diseases. In addition, melatonin is necessary for circadian rhythm. Studies have shown that melatonin levels are low in people with neurological diseases. Both preventive and therapeutic effects of melatonin are known for many diseases, including neurological diseases (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headache, etc.). Based on all these reasons, clinical trials of melatonin were performed and successful results were declared. CONCLUSIONS: In this review, biological and chemical knowledge of melatonin, its experimental effects, and the clinical impact on patients with neurological disorders were described. According to all of the beneficial results obtained from experimental and clinical trials, melatonin may have a prophylactic and therapeutic effect on neurological diseases. Strong collaboration between neurologists and health service policy makers is needed to encourage use of melatonin in the patients suffering from neurological diseases. Melatonin may be the solution we have been looking for.

Dexpanthenol reduces diabetic nephropathy and renal oxidative stress in rats.

Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress contributes to the development of diabetic complications. Dexpanthenol (Dxp) is the biological active form of pantothenic acid. We investigated whether Dxp administration could decrease oxidative stress as a way to treat renal complications of diabetes mellitus (DM). Thirty-two male Wistar albino rats were divided into four groups: control, Dxp, DM and DM + Dxp. Experimental diabetes was induced by a single dose of streptozotocin (STZ). After administration of STZ, the DM + Dxp group was administered 500 mg/kg Dxp intraperitoneally every day for 6 weeks. At the end of the study, blood glucose levels were measured and rats were sacrificed. Kidneys were embedded in paraffin, sectioned and stained with hematoxylin and eosin, and periodic acid-Schiff. The mean malondialdehyde levels, glutathione peroxidase, superoxide dismutase and catalase activities, and total antioxidant and total oxidant status also were measured. The control group was normal in histological appearance. We observed congestion, inflammation, glomerulosclerosis, tubular desquamation, loss of villi and hydropic degeneration in tubule cells in the DM group. Indicators of oxidative stress were elevated and antioxidant activity was reduced in the DM group compared to controls. In the DM + Dxp group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DM group. We found that Dxp exhibited ameliorative effects on STZ induced diabetic nephropathy by increasing antioxidant activity.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Liver Injury.

OBJECTIVE: We aimed to investigate the protective and therapeutic effects of dexpanthenol (DXP) on liver injuries induced by ischemia-reperfusion (IR) in an in vivo rat model. METHODS: Thirty-two rats were randomly divided into 4 experimental groups (n = 8 in each group: Sham, IR, DXP, and DXP+IR. DXP (500 mg/kg) was intraperitoneally administered for 30 min before 60 min of ischemia, followed by 60 min of reperfusion to rats in the DXP and DXP+IR groups. All rats were euthanized on day 10 to evaluate immunohistopathological changes as well as tissue levels of oxidants and antioxidants. RESULTS: IR decreased total glutathione (tGSH) levels in IR group when compared to the Sham group. DXP supplementation to IR group significantly ameliorated tGSH levels (P < .05). IR also elevated myeloperoxidase production compared to the Sham group, whereas DXP treatment prevented these hazardous effects. However, plasma superoxidedismutase, catalase, and malondialdehyde levels did not differ between the DXP+IR than the IR rats. Histologic tissue damage was reduced in the DXP and DXP+IR group. CONCLUSION: Liver IR is an inevitable problem during liver surgery. Our results suggested that DXP pretreatment suppressed oxidative stress and increased antioxidant levels in a rat model of liver IR.

Effects of melatonin on acetylsalicylic acid induced gastroduodenal and jejunal mucosal injury.

We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury.

Effects of molsidomine on retinal ischemia/reperfusion injury in rabbits.

We investigated the effect of molsidomine (MOL) on ischemia/reperfusion (I/R) injury. Rabbits were assigned to four groups: group 1, sham; group 2, I/R; group 3, MOL treatment for 4 days after I/R; group 4, MOL treatment for 1 day before I/R and 3 days after I/R. Retinal I/R was produced by elevating the intraocular pressure to 150 mm Hg for 60 min. Seven days after I/R, the eyes were enucleated. Retinal changes were examined using histochemistry. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) also were measured. We found a significant increase in the thickness of the outer nuclear layer of group 3 compared to the other groups. In groups 3 and 4, caspase-3 stained cells in the ganglion cell layer were decreased compared to group 2. We found a significant increase in caspase-3 stained cells in the inner nuclear layer (INL) of group 2 compared to the other groups. We found a significant increase in caspase-3 stained cells in group 3 compared to group 4 in the INL. The MDA level in group 2 was significantly higher than group 1 and MOL significantly decreased MDA levels in groups 3 and 4. We found that MOL protected the retina from I/R injury by enhancing antioxidative effects and inhibiting apoptosis of retinal cells.

Protective and therapeutic effects of molsidomine on radiation induced neural injury in rats.

We investigated the protective and therapeutic effects of molsidomine (MOL) in a rat model of whole brain radiotherapy (RT). Forty female rats were divided into five groups of eight: group 1, control; group 2, 15 Gy single dose RT (RT); group 3, 4 mg/kg MOL treated for 5 days (MOL); group 4, 4 mg/kg MOL for 5 days, 10 days after RT treatment (RT + MOL); group 5, 4 mg/kg MOL treatment for 5 days before RT treatment and for 5 days after RT treatment (MOL + RT). All rats were sacrificed on day 16. Neurodegenerative changes in the brain and tissue levels of oxidants and antioxidants were evaluated. The oxidative parameters were increased and antioxidant status was decreased in group RT compared to groups MOL + RT and RT + MOL. Histopathological examination showed that treatment with MOL after RT application and treatment with MOL before RT treatment decreased neuronal degeneration. No difference in neuronal appearance was found between groups RT + MOL and MOL + RT. MOL treatment protected the nervous system of rats and may be a treatment option for preventing RT induced neural injury.

Beneficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury.

This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine (AG), on radiotherapy (RT)-induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+RT and (v) RT+AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total oxidant status (TOS), total antioxidant capacity, oxidative stress index (OSI), blood urea nitrogen (BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT-treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT-treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT-treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT-induced kidney and testis injury.

The protective effects of apocynin on ionizing radiation-induced intestinal damage in rats.

BACKGROUND AND AIMS: Radiation colitis typically emerges during radiotherapy of intra-abdominal malignancies. While the underlying mechanism remains unclear, it is considered that free oxygen radicals act like cellular mediators to cause colonic damage. Apocynin (APO) prevents oxidative stress and apoptotic cell death by inhibiting NADPH oxidase, and preventing the formation of free oxygen radicals. The aim of the present study was to investigate the protective effect of APO, a strong antioxidant and antiinflammatory agent, on radiation induced colonic oxidative damage in rats. MATERIALS AND METHODS: Rats were randomly divided into four groups (n = 8/group). Group I (control group); Group II (Group RAD) received a single dose of 800 cGy ionizing radiation to the whole abdomen with a linear accelerator (LINAC); Group III (Group APO) received a single dose of 20 mg/kg of APO intraperitoneally for five days; Group IV (Group APO+RAD) received APO for five days before radiation exposure (similar to Group III), (similar to Group II). RESULTS: APO treatment prior to radiation led to protection in the biochemical and histopathological parameters. CONCLUSIONS: Our study shows that APO treatment before radiation improves radiation induced colonic injury in rats, by decreasing oxidative stress and apoptosis.

The analgesic effect of apelin-13 and its mechanism of action within the nitric oxide and serotonin pathways.

BACKGROUND: Apelin has various effects on a lot of systems such as central nervous system and cardiovascular system. This study investigated the possible analgesic effects of apelin-13 using the hot-plate and the tail-flick thermal analgesia tests in rats. We also evaluated the mechanism underlying the analgesic effects of apelin-13 by pretreating with Nw-nitro-L-arginine methyl ester (L-NAME) or ondansetron. MATERIAL & METHODS: Forty male rats were used. The rats were randomly assigned to five groups according to the treatment received: Group I: Control; Group II: Morphine; Group III: Apelin-13; Group IV: Apelin-13+L-NAME; Group V: Apelin-13+Ondansetron. Acute thermal pain was modeled using the hot-plate and the tail-flick tests. RESULTS: During the hot-plate test, i.p. Morphine and apelin-13 administered at zero- and 30 min produced significantly greater analgesic effects compared to the control. When the nitric oxide pathway was inhibited by administration of L-NAME with apelin-13, the analgesic effect continued. When apelin-13 and ondansetron were co-administered, the analgesic effect of apelin-13 disappeared at zero- and 30 min. During the tail-flick test, at 30 min, significantly higher levels of analgesia were observed in both the morphine and apelin group (which did not differ from each other) compared to the control group. L-NAME co-administered with apelin-13 did not affect the degree of analgesia, but apelin-13 co-administered with ondansetron was associated with a greater reduction in analgesia compared to the other groups. CONCLUSION: Our results demonstrate that apelin-13 exerts an analgesic effect; co-administration of apelin-13 and ondansetron inhibits antinociception, an effect apparently mediated by five-hydroxytryptamine-three (5-HT3) receptors. Hippokratia 2015; 19 (4): 319-323.

Combined usage of estrogen and melatonin restores bladder contractility and reduces kidney and bladder damage in ovariectomized and pinealectomized rat.

OBJECTIVE: The incidence of urinary bladder disturbances and renal structural changes and functional decline are found to increase with age. METHODS: We investigated the effect of melatonin treatment in addition to estrogen replacement therapy in pinealectomized (Px) and ovariectomized (Ovx) rats. 56 female Wistar rats were divided into seven groups, each containing eight animals: Sham, (Ovx), (Px), Px+Ovx, Px+Ovx receiving estrogen (Px+Ovx+E), Px+Ovx receiving melatonin (Px+Ovx+M) and Px+Ovx estrogen and melatonin supplemented (Px+Ovx+EM) group (EM group). We evaluated reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. The mean collagen fiber (CF)/smooth muscle (SM) ratio in the bladder wall and structure of the kidney were examined histolologically. We also recorded response of the bladder contractility to acetylcholine (Ach). RESULTS: Px and Ovx groups showed statistically significant reductions of antioxidant defenses, impaired Ach-evoked contraction, histological changes compared with the control group. Also, these changes were prominent in Px+Ovx group compared with all other groups. Both estrogen and melatonin reversed these changes however best restoration was observed in the EM group. CONCLUSIONS: Px performed in addition to Ovx led to a distinct increase in oxidative damage in bladder and renal tissue and deteriorate of the detrussor function. Either estradiol or melatonin replacement alone or in combination prevents significant alterations of tissue histology and bladder contractility following Ovx and Px. Thus, combination treatment appears to be the best method to restore both contractility and histomorphology of bladder and kidney tissues after Ovx and Px (Tab. 3, Fig. 4, Ref. 44).

The effect of melatonin on acetylsalicylic acid-induced kidney and testis damage.

The aim of this study was to evaluate the acute effect of high-dose acetylsalicylic acid (ASA) on kidney and testis, and the potential protective and therapeutic effects of melatonin on ASA-related pathology. A total of 40 rats were randomly divided into the following 5 groups (n = 8): group 1: control, not given any drug; group 2: only 200 mg/kg ASA was given; group 3: 5 mg/kg melatonin was given 45 min before administering 200 mg/kg ASA; group 4: 5 mg/kg melatonin was given 45 min after administering 200 mg/kg ASA; and group 5: only 5 mg/kg melatonin was given. The histopathological changes and the biochemical findings; such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), and blood urea nitrogen (BUN) as well as serum creatinine (Cr) levels were evaluated. ASA significantly increased MDA levels in both kidney and testis, whereas it significantly decreased the values of SOD, CAT, GPX, and GSH in kidney and CAT levels in testis. Melatonin significantly decreased MDA levels in kidney and ameliorated it in testis, whereas it caused elevation in the levels of antioxidants. BUN and Cr levels were higher after ASA, whereas these levels were diminished after melatonin administration. The improvement obtained by melatonin on ASA-induced histological alterations was more prominent when it was used after ASA in kidney and before ASA in testis. In this study, we demonstrated the beneficial effect of melatonin on high-dose ASA-related pathology of kidney and testis for the first time.

Effects of molsidomine against doxorubicin-induced cardiotoxicity in rats.

PURPOSE: To explore the protective and curative effects of molsidomine (MOL) on doxorubicin (DOX)-induced cardiac damage in the in vivo rat heart. METHODS: Forty rats were randomized into five groups (n = 8): (1) the control group; (2) the MOL group (10 mg/kg for 21 days); (3) the DOX group (a single dose of 20 mg/kg); (4) the DOX + MOL group (3 days after the single dose of DOX, 10 mg/kg MOL continued for 21 days), and (5) the MOL + DOX group (24 h after a 21-day regimen of 10 mg/kg MOL, a single dose of DOX). The rats were monitored for mean arterial blood pressure, heart rate, O2 saturation, and electrocardiography. Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) were determined. RESULTS: Blood pressure and O2 saturation values indicated a significant decrease in the DOX group compared with the control group. T negativity was observed in 4 of 8 rats in the DOX group, in 1 of 8 rats in the DOX + MOL group, and in 4 of 8 rats in the MOL + DOX group. MDA levels were significantly higher in the DOX group. SOD, GSH, and NO levels were significantly lower in the DOX group compared with the other groups. There was no statistically significant difference in the CAT levels in any of the study groups compared with controls. DOX treatment induced morphological alterations, such as disorganization of cardiomyocytes, loss of myofibrils, and cytoplasmic vacuolization in the heart. On the other hand, histological damage was significantly reduced in the DOX + MOL and MOL + DOX groups. CONCLUSION: This study implies that there are cardioprotective effects of MOL on DOX-induced cardiotoxicity.

Aminoguanidine prevents testicular damage-induced-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male rats.

In this study, it was aimed to determinate protective effects of aminoguanidine (AG) against reproductive toxicity caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant. Thirty-two rats were equally divided into four groups; the first group was kept as control and given corn oil as carrier. In second and third groups, TCDD and AG were orally administered at the dose of 2 µg kg(-1) per week and 100 mg kg(-1) per day for 45 days, respectively. In fourth group, TCDD and AG were given together at the same doses. Although TCDD significantly increased the formation of TBARS, it caused a significant decline in the levels of GSH, CAT, GPx and SOD in rats. On the other hand, AG, given together TCDD, reversed TCDD effects on TBARS SOD, GSH, GPx and CAT. In addition, sperm characteristics negatively affected and histopathological deformation occurred with TCDD exposure. However, AG treatment partly prevented these toxic effects of TCDD on spermatological parameters and histopathological changes. In conclusion, TCDD exposure induces testicular damage (oxidative stress, histopathological damage and sperm parameters), and AG treatment reversed TCDD-induced testicular damage in rats. Thus, AG may be useful for the prevention and treatment of TCDD-induced male infertility problems.

Chronic melatonin treatment reverses disruption of prepulse inhibition in pinealectomized and pinealectomized-plus-ovariectomized rats.

Although melatonin has been implicated in several neurophysiological systems, data on the relationship of melatonin with psychosis such as schizophrenia are limited and contradictory. Chronic effects of melatonin on sensorimotor gating deficits have also not been investigated yet. We investigated the neurobehavioral effects of chronic administration of melatonin in pinealectomized (Px) and ovariectomized (Ovx) rats. Px or Ovx or both operations were carried out together to the rats. The control group of rats was sham operated. A sham ovariectomy was carried out to Px rats, and vice versa. Fifth month later, melatonin (5mg/kg) or vehicle was injected to rats for 28 days. Then, prepulse inhibition (PPI) of acoustic startle reflex, startle amplitude and startle reflex latency was measured. Locomotor activity, accelerod performance measurements, novel object recognition and passive avoidance tests were also evaluated. Px and Px+Ovx rats had impaired PPI compared to control rats. Melatonin reversed the impairments of PPI induced by Px or Px+Ovx. While melatonin treatment had no effect on locomotor activity of control rats, it significantly increased the locomotor activity of Px and Px+Ovx rats. Melatonin treatment (5mg/kg/day, 28 days) reversed the locomotor hyperactivity caused by Ovx. Accelerod performance, passive avoidance, and object recognition responses of Px, Ovx or Px+Ovx rats were not different from the control group. Our results indicate that chronic melatonin deficiency by reason of Px results in impairment of PPI reflex and replacement of melatonin exerts beneficial effects on the impaired PPI reflex in Px and Ovx rats. Thus, melatonin may be useful in the treatment of some disorders characterized by sensorimotor gating deficits such as schizophrenia.

Effects of pinealectomy and exogenous melatonin on the brains, testes, duodena and stomachs of rats.

BACKGROUND: It is generally agreed that physiological levels of melatonin, a hormone secreted by the pineal gland, are important in protecting against oxidative stress-induced tissue damage. AIM: We investigated the effects that pinealectomy and the administration of exogenous melatonin have on the brains, testes, duodena and stomachs of rats. MATERIALS AND METHODS: Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, and catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD) and malondialdehyde (MDA) levels. The rats were divided into the following five groups (eight rats in each group): sham (non-Px), Px+ vehicle, Px+ melatonin (10 mg/kg given daily intraperitoneally for a week), melatonin and ethyl alcohol. RESULTS: The antioxidant levels in the tissue of Px rats were significantly lower than in those of the sham group. Administering melatonin significantly increased antioxidant levels (p < 0.05). The Px rats also showed a significant increase in MDA levels when compared to the sham group, and administering melatonin to the Px rats significantly reduced their MDA levels (p < 0.05). The severity of caspase-3 staining was lower in the Px+ melatonin group than in the Px+vehicle group. CONCLUSIONS: These findings suggest that significantly more oxidative and structural changes occur in rats' brains, spinal cords and testes after pinealectomy, but that this can be diminished by melatonin treatment. However, Px does not have important effects on the duodenum and stomach.

Therapeutic effects of ivabradine on hemodynamic parameters and cardiotoxicity induced by doxorubicin treatment in rat.

The aim of this study was to investigate the possible effects of ivabradine against doxorubicin (DOX)-induced cardiotoxicity in rats using hemodynamic parameters (electrocardiogram, heart rate (HR), and blood pressure), biochemical markers of oxidative stress, lactate dehydrogenase, aspartate transaminase, creatine kinase-MB, and histopathological analyses both in serum and tissue specimens. A total of 28 female rats were randomly assigned to 4 groups: (a) control (n = 6 rats), (b) DOX group (n = 7 rats), (c) DOX + ivabradine-treated group (n = 8 rats), and (d) ivabradine group (n = 7 rats). When the means of the four groups were compared, there was only a significant difference in the level of HR (p < 0.05). DOX treatment caused more HR elevation when compared to the control group, whereas ivabradine application after DOX treatment significantly reduced HR levels. Cardiomyocytes were revealed as normal histology in the light of both hematoxylin and eosin staining and immunostaining methods (caspase-3 and bcl-2) in all groups. The present study reported the therapeutic effects of ivabradine against DOX-induced cardiotoxicity accompanied by the hemodynamic and biochemical parameters.

Melatonin ameliorates cerebral vasospasm after experimental subarachnoidal haemorrhage correcting imbalance of nitric oxide levels in rats.

In the present study, we investigated the in vivo effects of melatonin on SAH-induced cerebral vasospasm and oxidative stress, resulting from SAH in an experimental rat model. Twenty-eight rats (225-250 g) were divided into four groups equally: group 1; control, group 2; SAH, group 3; SAH plus placebo, and group 4; SAH plus melatonin. We used double haemorrhage method for SAH groups. Beginning 6 h after SAH, 20 mg/kg melatonin or equal volume of 0.9% saline was administered intraperitoneally twice daily for 5 days to groups 3 and 4, respectively. Melatonin or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed at the end of this period. Brain sections at the level of the pons were examined by light microscopy. The lumen diameter and the vessel wall thickness of basilar artery were measured using a micrometer. The serum levels of cerebral vasodilator nitric oxide (NO), the brain levels of an intrinsic antioxidant superoxide dismutase (SOD) and a NO regulator arginase activities were measured. The brain levels of inducible nitric oxide (iNOS) and nitrotyrosine, a nitrosative stress parameter immunohistochemiacally determined. In conclusion, melatonin administration ameliorated cerebral vasospasm by increasing serum NO level and decreasing the brain the levels of arginase and oxidative stress. It is therefore possible that increased brain arginase activity after SAH may also have a significant role in the pathogenesis of vasospasm by limiting the availability of arginine for NO production.