Mustafa Sarsilmaz

The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

This study was designed to investigate the protective effects of caffeic acid phenethyl ester on carbon tetrachloride-induced liver damage in rats. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected with carbon tetrachloride every other day for 1 month, whereas rats in group III were injected with carbon tetrachloride and caffeic acid phenethyl ester every other day for 1 month. At the end of the experiment, all animals were killed by decapitation and their livers were removed. Liver tissues were processed for electron microscopy. Histopathologically, hepatocytes of rats treated with carbon tetrachloride had damage in the cytoplasmic organelles and nuclei membranes as well as an excessive lipid accumulation in the hepatocytes. However, those histopathological changes were reduced with the coadministration of carbon tetrachloride and caffeic acid phenethyl ester. We conclude that caffeic acid phenethyl ester treatment has the capability to prevent carbon tetrachloride-induced liver damage in rats.

To investigate the effects of melatonin and octreotide in the prevention of peridural fibrosis in an experimental rat model. A total of 36 rats were divided into three groups: Group I was laminectomized and not given any treatment. Group II received an intraperitoneal 30 microg/kg/day dose of octreotide for six weeks after the laminectomy. Group III rats were injected with melatonin 7.5 mg/kg/day for six weeks after the laminectomy. At the end of six weeks, plasma transforming growth factor beta-1 levels and peridural fibrous tissue hydroxyproline concentrations were determined and histopathological examinations was performed. Serum TGF-Beta1 levels of the octreotide and melatonin groups were found to be lower than the control group. The lower levels of TGF-Beta1 was statistically significant in both of the groups. Hydroxyproline levels of the octreotide and melatonin groups were found to be lower than that of the control group. The decrease was statistically significant only in the melatonin group. Peridural fibrosis scores of the octreotide and melatonin groups were lower than the control group. This histopathological improvement was statistically significant only in the melatonin group. Melatonin and octreotide prevented TGF-Beta1 increase in peridural fibrosis, but only melatonin significantly improved hyroxyproline levels and fibrosis scores as demonstrated.

AJA publishes new findings in basic and clinical (including modern, traditional and epidemiological) research on Andrology.

This study was undertaken to investigate the protective effects of melatonin against formaldehyde‐induced neurotoxicity in prefrontal cortex of rats. For this purpose, 21 male Wistar rats were divided into three groups. The rats in Group I were used as a control, while the rats in Group II were injected every other day with formaldehyde. The rats in Group III received melatonin daily while exposed to formaldehyde. At the end of 14‐day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for immunohistochemical evaluation. The levels of SOD and GSH‐Px were significantly decreased, and MDA levels, were significantly increased in rats treated with formaldehyde compared with those of the controls. In the immunohistochemical evaluation of this group, apoptotic cells were observed. However, increased SOD and GSH‐Px enzyme activities, and decreased MDA levels, were detected in the rats administered melatonin while exposed to formaldehyde. Furthermore, apoptotic changes caused by formaldehyde were decreased in these rats. The results of our study suggest that melatonin treatment prevents formaldehyde‐induced neuronal damage in prefrontal cortex. Copyright © 2006 John Wiley & Sons, Ltd.

The aim of this study was to examine the neurotoxicity of formaldehyde on prefrontal cortex and the protective effects of ω‐3 essential fatty acids against these toxic effects. For this purpose, 21 male Wistar rats were divided into three groups. The rats in group I comprised the controls, while the rats in group II were injected every other day with formaldehyde (FA). The rats in group III received ω‐3 fatty acids daily while exposed to formaldehyde. At the end of the 14‐day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for light microscopic and immunohistochemical evaluation. The levels of SOD and GSH‐Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Furthermore, in the microscopic examination of this group, formation of apoptotic bodies, pycnotic cells, and apoptotic cells including nuclear fragmentation and membrane budding were observed. However, increased SOD and GSH‐Px enzyme activities, and decreased MDA levels were detected in the rats administered ω‐3 fatty acids while exposed to formaldehyde. Additionally, cellular damage caused by formaldehyde was decreased, and structural appearance was similar to that of the control rats in this group. The biochemical and histological findings observed in all groups were also confirmed by immunohistochemical evaluation. It was determined that formaldehyde‐induced neuronal damage in prefrontal cortex was prevented by administration of ω‐3 essential fatty acids. Copyright © 2005 John Wiley & Sons, Ltd.

Carbon tetrachloride (CCl₄) is a volatile organic chemical, which causes tissue damage, especially to the liver and kidney. In experimental animals it has been shown to be carcinogenic. This study was designed to evaluate the effects of exogenous melatonin administration on the CCl₄-induced changes of some biochemical parameters in rat blood. Twenty-four male Wistar rats were randomly divided into three equal groups: Control, CCl₄ and CCl₄ plus melatonin (CCl₄+MEL). Rats in CCl₄ group were injected subcutaneously with CCl₄ 0.5 ml/kg in olive oil while rats in CCl₄+MEL group were injected with CCl₄ (0.5 ml/kg) plus melatonin (25 mg/kg in 10% ethanol) every other day for one month. Control rats were treated with olive oil. Serum urea, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (γ-GT), total iron, and magnesium levels were determined. Serum AST, ALT, total and conjugated bilirubin, ALP, γ-GT, and total iron levels were significantly higher in CCl₄-treated rats than in the controls, while urea, total protein, and albumin levels were significantly lower. Melatonin treatment did not cause a significantly change in serum urea, total protein, and albumin levels. However, the elevations in AST, ALT, total and conjugated bilirubin, ALP, γ-GT, and total iron levels induced by CCl₄ injections were significantly reduced by melatonin. On the other hand, melatonin administration significantly decreased serum magnesium levels. These results indicate that melatonin could be a protective agent against the CCl₄ toxicity in rats, most likely through its antioxidant and free radical scavenger effects. El tetracloruro de carbono (CCl₄) es un agente cancerígeno que causa daños orgánicos, especialmente en hígado y riñón. En este trabajo se evalúan los efectos de la administración de melatonina sobre los cambios inducidos por CCl₄ de algunos parámetros bioquímicos en suero de rata. Para ello, 24 ratas Wistar macho se dividieron en tres grupos (n=8): Control, CCl₄ y CCl₄ más melatonina (CCl₄+MEL). A las ratas del grupo CCl₄ se les inyectó diariamente CCl₄ (0,5 ml/kg, sc en aceite de oliva) durante un mes y a las ratas CCl₄+MEL se les inyectó además melatonina (25 mg/kg, sc en etanol al 10%) en días alterno. Las ratas control recibieron sólo aceite de oliva por vía subcutánea. Al final del tratamiento, se determinaron los niveles séricos de urea, creatinina, proteína total, albúmina, aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), bilirrubina total y conjugada, fosfatasa alcalina (ALP), gamma-glutamil transpeptidasa (γ-GT), hierro total y magnesio. Los valores de AST, ALT, bilirrubina total y conjugada, ALP, γ-GT, y de hierro total fueron significativamente mayores en suero de ratas tratadas con CCl₄ que en los controles, mientras que los niveles de urea, proteína total, albúmina fueron significativamente menores. El tratamiento de melatonina no modificó significativamente los cambios en la urea, proteína total y albúmina sérica. Sin embargo, los increamentos en los niveles de AST, ALT, bilirrubina total y conjugada, ALP, γ-GT y hierro total en suero inducidos por CCl₄ se redujeron significativamente por la hormona. Además, la administración de melatonina provocó disminución de los niveles de magnesio. Los resultados indican que la melatonina puede ser un protector contra la intoxicación por CCl₄ en ratas, probablemente por sus efectos antioxidantes.

The aim of this study was to examine the protective effects of melatonin against CCl₄‐induced hepatotoxicity in the rat. Twenty‐four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl₄ for 1 month, whereas rats in group III were injected every other day with CCl₄ and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl₄ than in the controls. When rats injected with CCl₄ were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl₄‐injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl₄ were lost from rats treated with CCl₄ and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl₄‐induced liver damage in rats. Copyright © 2004 John Wiley & Sons, Ltd.