Gözde Erkanlı

Melatonin Protects Against Oxidative Organ Injury in a Rat Model of Sepsis

PurposeBased on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against sepsis-induced oxidative organ damage in rats.MethodsSepsis was induced by cecal ligation and puncture (CLP) in Wistar albino rats. Animals subjected to CLP and sham-operated control rats were given saline or melatonin 10 mg/kg intraperitoneally 30 min before and 6 h after the operation. The rats were killed 16 h after the operation and the biochemical changes were investigated in the liver, kidney, heart, lung, diaphragm, and brain tissues by examining malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. We also examined the tissues microscopically.ResultsSepsis resulted in a significant decrease in GSH levels and a significant increase in MDA levels and MPO activity (P < 0.05–P < 0.001) showing oxidative damage, which was confirmed by histological examination. Melatonin clearly reversed these oxidant responses and the microscopic damage, demonstrating its protective effects against sepsis-induced oxidative organ injury.ConclusionThe increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage. Melatonin, by its free radical scavenging and antioxidant properties, ameliorated oxidative organ injury. Thus, supplementing antiseptic shock treatment with melatonin may be beneficial in the clinical setting.

Melatonin protects against ischemia/reperfusion injury in skeletal muscle.

Abstract:  Melatonin has been shown to diminish ischemia‐reperfusion (I/R) injury in many tissues. The main aim of this study was to evaluate the protective antioxidant effect of melatonin in skeletal muscle during I/R injury. Wistar albino rats were randomly divided into three groups. Hindlimb ischemia was achieved by clamping the common femoral artery in two groups but not in control group. Limbs were rendered ischemic for 1.5 hr; at the end of the reperfusion period of 1.5 hr muscle tissue samples were taken for the histological evaluation and biochemical analysis. Melatonin (10 mg/kg) was injected i.p. in the I/R + Mel group at the onset of ischemia whereas the vehicle solution was injected in the I/R group. In I/R + Mel group histological damage was significantly less than in the I/R group (P < 0.001). In the I/R + Mel group, the mean malonedialdehyde level was lower than in the I/R group (P < 0.01) and was quite near to the levels in the control group (P > 0.05). Glutathione levels were found to be reduced in the I/R group compared with the control (P < 0.01) and I/R + Mel group (P < 0.01). Melatonin has a protective effect against I/R injury in skeletal muscle and may reduce the incidence of compartment syndrome, especially after acute or chronic peripheral arterial occlusions.

Exposure to continuous darkness ameliorates gastric and colonic inflammation in the rat: both receptor and non-receptor-mediated processes.

Background and Aim:  Melatonin is a hormone involved in the transduction of photoperiodic information, and appears to modulate a variety of neural and endocrine functions. The present study was designed to determine the impact of continuous darkness (CD) on acute gastric and colonic inflammation and the involvement of melatonin receptors in the darkness‐related alterations in oxidant gut injury.

Octreotide ameliorates sepsis-induced pelvic inflammation in female rats by a neutrophil-dependent mechanism.

Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, accompanied by the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. The aim of this study was to investigate the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against sepsis-induced oxidative damage in the uterine and ovarian tissues of rats. Sepsis was induced by caecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or OCT (50 microg/kg, i.p.; Novartis) immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and serum TNF-alpha levels and tissue malondialdehyde (MDA) content, glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the uterus and ovaries. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, while the extent of tissue injuries was analyzed microscopically. Sepsis increased serum TNF-alpha levels and resulted in decreased GSH levels and increased MDA levels, MPO activity and collagen contents in both the uterus and the ovaries (p<0.05-0.001) indicating the presence of the oxidative damage, as also confirmed by histological analysis. On the other hand, OCT administration reversed these oxidant responses and reduced the severity of microscopic damage (p<0.001). In conclusion, OCT protects against sepsis-induced oxidative injury of the uterine and ovarian tissues by diminishing neutrophil infiltration, an important source of oxygen free radicals. Our results suggest that OCT may be of therapeutic value in ameliorating sepsis-associated pelvic inflammation.

Time-dependent changes in distribution of basic fibroblast growth factor immunoreactive cells in rat hippocampus after status epilepticus

Abstract Objective: In this study, we aimed to examine time-dependent morphologic changes and quantitative alterations in the density of basic fibroblast growth factor (bFGF)-immunoreactive (ir) astrocytes and CA2 pyramidal neurons in dorsal hippocampus of rats after status epilepticus (SE) induced by kainic acid (KA) injection. Methods: Wistar albino rats were injected with saline or KA i.p. to investigate time-dependent alterations in morphology and the number of bFGF-ir astrocytes and neurons in the dorsal hippocampus 15, 30 and 90 days after KA injection. Results: Fifteen days after KA injection, gliosis was present throughout the hippocampus and neuronal loss was evident in CA1 and CA3 regions, which was more severe after 30 and 90 days. KA-injected rats demonstrated significantly increased number of both bFGF-ir astrocytes throughout the hippocampus and pyramidal neurons in CA2 after 15 days and decreased number after 30 and 90 days. Conclusion: The decrease in the number of bFGF-ir astroglia and neurons in long term after KA injection may indicate a decrease in the production of bFGF and/or number of bFGF-ir cells, suggesting that protective effects of bFGF might be altered during epileptogenesis in the hippocampus.

Time-dependent changes in distribution of basic fibroblast growth factor immunoreactive cells in hippocampus after kainic acid injection in rat pups

Five‐day‐old Wistar albino rats were injected with kainic acid (KA) or saline i.p. to investigate time‐dependent alterations in morphology and number of basic fibroblast growth factor (bFGF) immunoreactive (‐ir) astrocytes and neurons in hippocampus at 15, 30, and 90 days after the injections. Sections were stained with cresyl violet for morphological evaluation and bFGF immunohistochemistry was used for quantitative evaluation of bFGF‐ir cell density. Fifteen days after KA injection, there was gliosis but no neuronal loss although disorganization in CA1, CA3, CA4 pyramidal layers and neuronal loss were evident 30 and 90 days after the injection. KA injected rats demonstrated significantly increased number of bFGF‐ir astrocytes throughout the hippocampus and pyramidal neurons in CA2 after 15 days and decreased number of bFGF‐ir cells after 30 and 90 days. The decrease in the number of bFGF‐ir astroglia and neurons in long term after KA injection may indicate a decrease in the production of bFGF and/or number of bFGF‐ir cells suggesting that protective effects of bFGF may be altered during epileptogenesis in hippocampus.

A New Cause of Male Infertility After Cisplatin Exposure: The Effect of Cisplatin on Y Chromosomes

OBJECTIVES To investigate the impact of cisplatin (CP) on the testes-specific protein, Y-linked (TSPY) gene situated on the Y chromosome. METHODS The control group consisted of 10 rats. Group IIA consisted of 15 rats that underwent orchiectomy and received three cycles of 1 mg/kg, 2.5 mg/kg, or 5 mg/kg CP. Group IIB was exposed to the same doses of three cycles of chemotherapy but was examined after 3 months of chemotherapy. Group III was exposed to the same doses of chemotherapy without initial orchiectomy. Reverse transcriptase polymerase chain reaction for TSPY messenger ribonucleic acid (mRNA) and immunohistochemical staining for histone 2B were performed on the testes. Results were evaluated by one-way analysis of variance. RESULTS Compared with the controls, the expression of TSPY mRNA in Group IIA after exposure to 1 mg/kg CP did not change; however, mRNA levels after exposure to 2.5 mg/kg and 5 mg/kg CP were decreased by 40% and 78%, respectively. In Group III after exposure to the same doses of CP, mRNA levels decreased by 30%, 87.5%, and 88%, respectively. The expression of TSPY was at normal levels except in rats that received 5 mg/kg CP in Group IIB. Immunohistochemical study revealed that histone 2B expression was decreased in a dose-dependent manner. None of the rats from any of the groups died during the study period. CONCLUSIONS Decreased TSPY expression after CP exposure might be another mechanism for male infertility.