Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study.

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.

Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro voltammetric study.

The purpose of this study was to clarify the relationship between neuron cells and astrocyte cells in regulating glutamate toxicity on the 10th and 20th day in vitro. A mixed primary culture system from newborn rats that contain cerebral cortex neurons cells was employed to investigate the glutamate toxicity. All cultures were incubated with various glutamate concentrations, then viability tests and histological analyses were performed. The activities of glutamate transporters were determined by using in vitro voltammetry technique. Viable cell number was decreased significantly on the 10th day at 10(-7) M and at 10(-6) M glutamate applications, however, viable cell number was not decreased at 20th day. Astrocyte number was increased nearly six times on the 20th day as compared to the 10th day. The peak point of glutamate reuptake capacity was about 2 × 10(-4) M on the 10th day and 10(-3) M on the 20th day. According to our results, we suggested that astrocyte age was important to maintain neuronal survival against glutamate toxicity. Thus, we revealed activation or a trigger point of glutamate transporters on astrocytes due to time since more glutamate was taken up by astrocytes when glutamate transporters on the astrocyte were triggered with high exogenous glutamate concentrations. In conclusion, the present investigation is the first voltammetric study on the reuptake parameters of glutamate in vitro.

Protective effect of L-carnitine in a rat model of retinopathy of prematurity.

AIM: To investigate the effects of L-carnitine (LC) on rats with oxygen-induced retinopathy. MATERIALS AND METHODS: The study was conducted on 40 Sprague Dawley rat pups. The rat pups were randomly divided into 4 groups: group 1 (n = 10) the healthy control group with intraperitoneal 0.1 mL/day physiological saline injection; group 2 (n = 10), exposed to hyperoxygen, did not receive LC but received 0.1 mL/day physiological saline intraperitoneally; group 3 (n = 10), exposed to hyperoxygen and received 100 mg/kg/day LC intraperitoneally; group 4 (n = 10), exposed to hyperoxygen and received 200 mg/kg/ day LC intraperitoneally. After postnatal day 20, the rat pups were killed and an histological examination was performed on the eyes, in addition to the detection of plasma malondialdehyde (MDA) levels. RESULTS: The retinal and choroidal histopathological changes due to hyperoxygen were less in group 3 and minimal in group 4 compared with group 2. Compared with the healthy control group, the increase in the MDA levels in group 2 was significant (P <0.05). Compared with group 2 there was a significant (P < 0.05) decrease in the MDA levels in groups 3 and 4. CONCLUSION: LC has beneficial effects on oxygen-induced retinopathy in rats in terms of histopathological changes and MDA levels.

In vitro evaluation of long-term cytotoxic response of injection-molded polyamide and polymethyle metacrylate denture base materials on primary fibroblast cell culture.

OBJECTIVE: This study investigated the long-term cytotoxic response of thermoplastic polyamide and conventional polymethyle metacrylate (PMMA) denture base materials. MATERIALS AND METHODS: Twenty discs were prepared for each polyamide, heat and cold cured PMMA denture base resins (totally 60) and divided into four sub-groups (n = 5). Cytotoxicity was assessed with the direct cell contact method using cell viability and neutral red (NR) uptake assay. Each sub-group was tested at initial and after being aged for 24 h, 1 week and 8 weeks with artificial saliva according to ISO 10993 standards. RESULTS: There were no significantly difference among the materials and control groups after initial, 24 h and 1 week testing. In 24 h testing, only Deflex was more toxic according to the Control group (p < 0.05). After 8 weeks of aging with artificial saliva, all materials were significantly cytotoxic when compared to the control group. QC20 was more toxic than Deflex and SC Cold Cure (p < 0.05). There were significant differences between the 8 week aging group and the initial, 24 h and 1 week testing for all materials (p < 0.05). CONCLUSIONS: Cytotoxicity of all tested denture base materials increased significantly after the long-term aging. Therefore, long-term aging may be useful to determine a dental material's toxicity. Polyamide denture base material had a similar toxicity profile with conventional heat- and cold-cured PMMA.

Neuroprotective effect of acute interferon-beta 1B treatment after spinal cord injury.

AIM: The purpose of this trial was to investigate the effect of a well known immunomodulator -interferon beta- on traumatized spinal cord in terms of biochemical and histopathological features. MATERIAL AND METHODS: Twenty-four rats were used in this trial. The rats were divided into 3 groups. In the first group of rats, spinal cord injury was created by the weight drop method and interferon beta was administered. In the second group, physiological saline was administered. Third group was used as control. Rats were sacrificed 24 hours following trauma. Heat shock protein 70 levels were measured in the spinal cord samples and the samples were examined histopathologically. RESULTS: When the rats in the physiological saline and control groups were compared to rats treated with interferon beta 1b, those treated with interferon beta 1b revealed significant increases in the heat shock protein 70 levels in tissues, and histopathological examination revealed decreases in polymorphonuclear leucocyte infiltration, haemorrhage, oedema and necrosis. CONCLUSION: Although, the results of the study indicated that interferon beta might have some healing effects via increasing the cellular heat shock protein 70 on spinal cord injuries, more studies are needed.

Neuroprotective effect of ACE inhibitors in glutamate - induced neurotoxicity: rat neuron culture study.

AIM: Glutamate is known to be neurotoxic at concentrations of 10-6M and 10-7M. Angiotensin converting enzyme (ACE) inhibitors can be assumed to be neuroprotective as they open the mitochondrial adenosine triphosphate-sensitive potassium channels by inhibiting the degradation of bradykinin. In this study, we investigated whether the ACE inhibitors captopril, ramipril and perindopril have protective effects in glutamate-induced neurotoxicity in newborn rat cerebral cortex cell cultures. MATERIAL AND METHODS: Viability tests were performed among ACE inhibitors by constituting groups of control and 10-7M and 10-6M glutamate doses in newborn rat cortex cultures. RESULTS: While the mean viable cell number was 0.47±0.06 in the control group, it was 0.37±0.03 in the group exposed to 10-7M glutamate (p < 0.05) and 0.37±0.01 in the group exposed to 10-6M glutamate (p < 0.05). Captopril was used at a dose of 10 µM, perindopril was used at a dose of 1 µM, and ramipril was used at a dose of 30 µM against 10-7M and 10-6M glutamate. Ramipril and perindopril reversed the toxicity against 10-6M glutamate (p < 0.05). The neuroprotective properties of captopril, perindopril and ramipril were not found to be statistically significant against 10-7M glutamate at the doses mentioned above. CONCLUSION: Data obtained from this study indicate that ramipril and perindopril can prevent 10-6M glutamate-induced neurotoxicity.