Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats

Background and Aim:

Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury.

Materials and Methods:

Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure.

Results:

The I/R group''s TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes.

Conclusion:

Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.     

Protective effect of astaxanthin against cisplatin-induced gastrointestinal toxicity in rats

European Surgery - The aim of the present study was to demonstrate astaxanthin’s attenuating effects against cisplatin (CIS)-induced gastrointestinal toxicity in a rat model....     

Whortleberry protects kidney against the cisplatin-induced nephrotoxicity: an experimental study

Purpose: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats.

Material and methods: This study included 48 female Sprague–Dawley rats weighing 263.68?±?8.29?g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16?mg/kg cisplatin +100?mg/kg whortleberry, and 16?mg/kg cisplatin +200?mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (μm²), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p?Results: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p?p?Conclusions: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.     

Relationship between airway colonization, inflammation and exacerbation frequency in COPD

RATIONALE: To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). RESULTS: BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). CONCLUSION: The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.     

Situation awareness in obsessive-compulsive disorder

Past studies have suggested that OCD patients suffer memory impairment on tasks using complex stimuli that require memory for combined elements to be maintained, but not for more simplistic memory tests. We tested this with 42 OCD patients and 42 healthy controls performed a computerized situation awareness task. In addition, participants completed the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and Maudsley Obsessive-Compulsive Inventory (MOCI). The OCD patients had poorer accuracy in integration/comprehension and perception levels than controls. There were significant correlations between situational awareness scores (i.e., visuo-spatial monitoring and processing) and Y-BOCS obsession–compulsion and slowness and doubt scores of MOCI in OCD patients. In addition, there were also significant correlations between situational awareness and controlling, cleaning, slowness, rumination and total scores of MOCI in control group. Results indicated that (I) OCD patients have problems of perception, integration, and comprehension of complex visual perceptions; (II) situation awareness deficits associated with severity and prevalence of obsessions and compulsions.     

The effect of gadolinium‐based contrast agents on rat testis

Previous studies have reported that repeated administrations of linear gadolinium‐based contrast agents lead to their accumulation in the brain and other tissues in individuals with normal renal functions. The purpose of this prospective animal study was to investigate the effect of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium‐based contrast agents (GBCAs) on rat testis tissue and to compare these molecules in terms of tissue damage. Thirty‐two male Sprague‐Dawley rats were kept without drugs for 5 weeks after administration of 0.1 mmol mg^?1 kg^?1 (0.2 ml/kg) gadodiamide and gadoteric acid for 4 days over 5 weeks. Biochemical, histopathological and immunohistochemical changes in testis tissue were evaluated at the end of 10 weeks. When used in repeated clinical doses, gadolinium was observed to increase apoptosis in the Leydig cells of the rat testis, and to increase serum Ca⁺² levels and reduce testosterone levels (p < .05). Although the difference was not statistically significant, a greater loss of spermatozoa and immature germinal cell accumulation were observed in the seminiferous tubule lumen in the GBCA groups compared with the control and saline groups (p > .05). Both linear and macrocyclic contrast agents have toxic effects on testis tissue, irrespective of the type of drug.     

Neurological soft signs in schizophrenia and obsessive compulsive disorder spectrum

Obsessive compulsive symptoms are more frequent in patients with schizophrenia compared to normal population. Patients with obsessive compulsive disorder may also exhibit psychosis-like symptoms. Based on these findings, it has been suggested that there is a spectrum of disorders between OCD and schizophrenia. We compared two OCD groups (with good and poor insight) and two schizophrenia groups (with and without OCD) in this recommended spectrum especially in terms of neurological soft signs (NSSs) associated with sensory integration. The schizophrenia with OCD (schizo-obsessive) group exhibited worse performance than the schizophrenia group (p = 0.002) in only graphesthesia tasks. Moreover, schizo-obsessive patients exhibited worse performance compared to OCD patients in terms of graphesthesia (p = 0.001) and audiovisual integration (p = 0.001). Interestingly, OCD patients with poor insight tended to exhibit graphesthesia deficit in a similar manner to schizo-obsessive patients rather than OCD patients. According to our results, graphesthesia disorder is strongly associated both with OCD and schizophrenia. This suggests that neurodevelopmental disorders that lead to graphesthesia disorder overlap in comorbid OCD and schizophrenia patients.     

Radioprotective effect of endogenous melatonin secretion associated with the circadian rhythm in irradiated rats

Abstract

Purpose: We investigated the radioprotective effect of endogenous melatonin release at different times associated with the circadian rhythm on head and neck radiotherapy.

Materials and methods: Two groups of animals were subjected daily to 8?Gy single fraction radiotherapy in the head and neck region from 5:00 to 6:00 (the morning group) or from 19:00 to 20:00 (the evening group). Corresponding untreated groups served as controls. Submandibular glands from rats sacrificed on the seventh day after irradiation were assessed biochemically and histopathologically. Melatonin, malondialdehyde and superoxide dismutase levels in blood collected immediately prior to irradiation were measured with rat-specific ELISA kits.

Results: In irradiated rats, melatonin, malondialdehyde and superoxide dismutase levels were significantly higher in the evening group than in the morning group. In nonirradiated rats, melatonin and superoxide dismutase levels were significantly higher in the evening group than in the morning group. The areas of seromucous acinar cells were similar between the irradiated and nonirradiated evening groups, but the area was higher in the evening irradiated group than in the morning irradiated group.

Conclusion: Consideration of endogenous melatonin secretion associated with the circadian rhythm may offer new therapeutic solutions for the complications of head and neck radiotherapy.     

Effect of infliximab against cisplatin-induced nephrotoxicity

Objectives:

To investigate whether infliximab (Ib), an inhibitor of tumor necrosis factor alpha (TNF-α), prevents cisplatin (Cis)-induced nephrotoxicity.

Methods:

The study was performed in the Department of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey, between November 2012 and May 2013. Thirty male Wistar albino rats were divided into 3 groups, a control group, a Cis group, and a Cis+Ib group. The animals of the Cis group were injected with a single dose (7 mg/kg) of Cis intraperitoneally. The animals of the Cis+Ib group were injected with a single dose (7 mg/kg) of Ib 72 hours prior to Cis injection.

Results:

The TNF-α, interleukin-1 beta (IL-1β), nitric oxide (NO) and adenosine deaminase (ADA) levels of the Cis group were higher than both the control group TNF-α (p<0.001), IL-1a (p<0.001), NO (p<0.001) and ADA (p<0.001), and the Cis+Ib group TNF-α (p<0.001), IL-1β (p<0.001), NO (p<0.001), and ADA (p=0.003). Histopathological examination revealed extensive damage in the Cis group, while the damage in the Cis+Ib group was lower. While the carbonic anhydrase II (CA-II) level of the Cis group was lower than both groups, it was similar in the Cis+Ib and the control groups.

Conclusion:

Infliximab acts against Cis-induced nephrotoxicity by a strong inhibition of TNF-α. Additionally, the combination of these 2 drugs does not obviously change the level of CA-II.Cisplatin (Cis) is an antineoplastic drug used to treat solid tumors. Although it is used in most chemotherapy regimens, its nephrotoxic effect is a common problem. The mechanisms for Cis-induced nephrotoxicity have been attributed to renal cell apoptosis, oxidative stress, and inflammation.1,2 Cisplatin leads to the formation of reactive oxygen species (ROS) by increasing the release of pro-inflammatory cytokines such as tumor necrosis alpha (TNF-α), stimulating apoptosis through the direct effect of the cytokines, and increasing inflammation.3 Moreover, it causes nephrotoxicity by increasing the turnover of purine metabolism to its metabolites.4 Cisplatin induced nephrotoxicity is one of the important side effects that limit the use of Cis. Therefore, effective treatment is still sought to prevent it. Infliximab (Ib) is a potent TNF-α inhibitor that can safely be used to treat many chronic diseases with inflammation.5 Previous studies have shown that Ib prevents organ damage,6,7 and decreases nitric oxide (NO) and ROS formation.8 It has no nephrotoxic effect and can be used in patients with renal impairment.9 Carbonic anhydrase II (CA-II), which is a zinc metalloenzyme, catalyzes the reversible hydration reaction of carbon dioxide form carbonic acid. It is found in many tissues, mainly the kidneys.10 Over-expression of CA-II is observed in many cancers, including renal cell cancer.11 This condition leads to cancer cell growth and invasion. On the contrary, the suppression of CA-II or its deficiency leads to metabolic acidosis.12 In this study, we aimed to investigate whether Ib could prevent cis-induced nephrotoxicity, and whether this combination would affect the CA-II enzyme.