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Objective: 5-Fluorouracil (5-FU), a widely administered anti-cancer drug, causes gastrointestinal damage through various mechanisms. This study aimed to investigate the ameliorative effect of silk fibroin (SF), which has anti-inflammatory and antioxidant properties, against 5 FU-induced gastrointestinal damage. Materials and methods: Wistar albino rats were divided into 3 groups; Control group, 5-FU group (30mg/kg/day on days 0, 2, 4), and 5-FU+SF (30 mg/kg/day 5-FU on days 0, 2, 4 + 600 mg/kg/day SF for 14 days). At the end of the experiment, stomach and intestinal tissue samples were collected and immunohistochemically iNOS, caspase-3, CD4+ and CD8+ were measured. Besides, structural damage was assessed with hematoxylin-eosin and caspase-3 and 9 activities were evaluated using western blot analysis. Results and Discussion: It was determined that iNOS, caspase-3, caspase-9 activities, CD4+ and CD8+ levels and structural damage significantly increased in both stomach and intestinal tissues. Furthermore, elevated markers were regressed almost to control levels in SF administrated group. Conclusion: SF may have an ameliorative effect, thus reducing the gastrointestinal damage caused by 5 FU. More clinical and scientific research should be conducted as the silk fibroin may be a suitable candidate against the adverse effects of chemotherapeuic agents. [ABSTRACT FROM AUTHOR]

Introduction: We examined the effects of chitosan (CTS) for reducing cisplatin (CIS)-induced hepatorenal toxicity in a rat model. Methods: A hepatorenal toxicity model was established by administering a single dose of 7 mg/kg CIS intraperitoneally (i.p) to Wistar albino rats. After seven days of once-daily normal saline or CTS (200 mg/kg; po) treatment, liver and kidney tissue samples were obtained from rats and Bcl-2/Bax ratio and caspase-3 expression levels were evaluated by Western blotting method. Histologically, structural damage was measured under a light microscope, and the degree of damage to organs was evaluated by a scoring system. Results: CIS-induced hepatorenal damage was reversed with CTS treatment in the renal and hepatic tissues (p<0.05). Overall, CISinduced increases in apoptotic parameters, Bcl-2/Bax ratio and caspase-3 expression, were reversed by CTS treatment (p<0.05). Conclusion: It was determined that CTS, a biopolymer, may have a protective effect by preventing hepatorenal damage caused by CIS. [ABSTRACT FROM AUTHOR]

d -cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72 h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex. [ABSTRACT FROM AUTHOR]

Objective: The B-cell lymphoma/leukemia-2 (Bcl-2) family of proteins governs mitochondrial membrane permeability where the programmed apoptotic process is controlled by the balance between proapoptotic (Bax) and antiapoptotic (Bcl-2) proteins. We aimed to investigate the [Bcl-2]/[Bax] in different brain regions in a post-traumatic stress disorder rat model. Methods: Female Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter) in reversed 12 h light/dark cycle. The rats received intraperitoneal saline, fluoxetine (2.5 mg/kg/day) or propranolol (10 mg/kg/day) for 7 days between exposure sessions. Following exposure to the trauma reminder, elevated plus maze experiments were done. Immunoblotting was used to quantify [Bcl-2] and [Bax] proteins in the homogenates of the dorsal hippocampus, the frontal cortex and the amygdaloid complex. Results: Fluoxetine reversed the increases in the anxiety indices and the freezing times. In the amygdaloid complex and the frontal cortex, the [Bcl-2]/[Bax] decreased in the traumatized control rats significantly (p<0.0001), but not in the dorsal hippocampus. Although the fluoxetine treatment reversed the apoptotic changes but propranolol failed and caused proapoptotic proteins to increase. Conclusion: These results may suggest a neuroprotective role for fluoxetine but not for propranolol. [ABSTRACT FROM AUTHOR]

Abstract: This study shows the possible contribution of muscarinic receptors in the pathophysiology of post-traumatic stress disorder. Sprague-Dawley rats of both sexes were exposed to dirty cat litter (trauma) for 10min and the protocol was repeated 1 week later with a trauma reminder (clean litter). The rats also received intraperitoneal fluoxetine (2.5, 5 or 10mg/kg/day), propranolol (10mg/kg/day) or saline for 7 days between two exposure sessions. Functional behavioral experiments were performed using elevated plus maze, following exposure to trauma reminder. Western blot analyses for M1, M2, M3, M4 and M5 receptor proteins were employed in the homogenates of the hippocampus, the frontal cortex and the amygdaloid complex. The anxiety indices increased from 0.63±0.02 to 0.89±0.04 in rats exposed to the trauma reminder. The freezing times were also recorded as 47±6 and 133±12s, in control and test animals respectively. Fluoxetine or propranolol treatments restored the increases in the anxiety indices and the freezing times. Female rats had higher anxiety indices compared to males. Western blot data showed increases in M2 and M5 expression in the frontal cortex. Expression of M1 receptors increased and M4 subtype decreased in the hippocampus. In the amygdaloid complex of rats, we also detected a down-regulation of M4 receptors. Fluoxetine and propranolol only corrected the changes occurred in the frontal cortex. These results may imply that muscarinic receptors are involved in this experimental model of post-traumatic stress disorder. [Copyright &y& Elsevier]