Does Boric Acid Inhibit Cell Proliferation on MCF-7 and MDA-MB-231 Cells in Monolayer and Spheroid Cultures by Using Apoptosis Pathways?

Most breast cancers originate in the lobules or ducts of the breast. Breast cancer as the second main cause of death among women in the world is the most common kind of cancer in women. Studies have been conducted to find the optimal treatment for breast cancer. Moreover, the therapeutic effects of different drugs and substances on this disease have been intensively researched. Boric acid accounts for 96% of the boron content in body fluids, and its derivatives are absorbed by the human body. It is assumed to be represented as (B(OH)2). Experimental studies have shown a reduction of cell proliferation and stimulation of apoptosis in some melanoma, prostate, and colon cancer cell lines through boric acid. The aim of this study was to investigate if boric acid could be used for treating breast cancer. The impacts of boric acid on the human breast carcinoma cell lines MCF-7 and MDA-MB-231 were studied with TUNEL, BrdU, caspase-3, and endo-G immunohistochemical studies in 3D and 2D culture systems. Furthermore, we conducted a qRT-PCR study to show changes in the expression of some genes involved in apoptosis. Suppression of cell proliferation through boric acid-inducing apoptosis was observed both in 3D and 2D culture conditions. These results are compatible with the gene expression results. The ENDOG, CASP3, CASP8, and CASP9 gene expression significantly changed at all time intervals in MCF-7 and MD-MB-231 cell lines boric acid can potentially treat breast cancer as an anti-cancer agent candidate.

Back to school readiness scale for children with oncological problems: 7-18 years of age.

INTRODUCTION: Childhood cancers are one of the important health problems in both developed and underdeveloped countries. The cancer treatment process is a difficult period that can last for months or years, interrupt school activities for a while, or even cause them to leave completely, and require long-term hospitalization. PURPOSE: This study was carried out to develop the Back to School Readiness Scale for Children with Oncological Problems: 7-18 years of age, and to establish its validity and reliability. METHOD: The research is a methodological study and the validity and reliability study of a developed scale was conducted. RESULTS: Kaiser-Meyer-Olkin (KMO) value was determined as 0.951. As a result of Bartlett's test analysis, Chi-Square value is 6261.566, degree of freedom is 703 and the value found is significant (p = 0.00, p < 0.05). While the loadings of the items on the first factor vary between 0.79 and 0.46, the loads on the second factor vary between 0.76 and.47. The item-total-test correlation value is 0.63. Total Croncabh alpha (α) value of the scale is 0.97. CONCLUSION: Back to School Readiness Scale for Children with Oncological Problems: 7-18 years of age is a valid and reliable measurement tool. PRACTICE IMPLICATIONS: Returning to school is a difficult process for children living with cancer due to long-term hospitalization. This scale can be used by both pediatric nurses and school nurses to evaluate children's return to school. Additionally, children and families can get an idea about preparing for returning to school by applying this scale.

Apoptotic effects of Phlomis armeniaca mediated biosynthesized silver nanoparticles in monolayer (2D) and spheroid (3D) cultures of human breast cancer cell lines.

The purpose of current research was to assess the apoptotic effects of biofabrication silver nanoparticles (AgNPs) mediated by the aqueous extract of Phlomis armeniaca on human breast cancer cells (MCF-7 and MDA-MB-231) in monolayer (2D) and spheroid (3D) cultures. The biosynthesized AgNPs were characterized by UV-Vis spectrophotometer (the peaks of resonances at 432 nm), scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). 1-20 µM/mL AgNPs were applied to MCF-7 and MDA-MB-231 cell lines to determine IC50 values at 24, 48 and 72nd h and were found to be 10 µM/mL for both cell lines. Immunohistochemical staining results of BrdU, TUNEL, caspase-3 and Endo G in both 2D and 3D cultures and gene expression levels of caspases (caspase-3, -8 and -9) and Endo G were evaluated. Moreover, the total oxidant/antioxidant status (TOS-TAS) due to AgNPs application in both cell culture mediums was evaluated. AgNPs treatment results in both cell lines in both 2D and 3D cultures showed a significant decrease in the BrdU labeling index, while large amounts of cells were labelled with TUNEL and Endo G. In 2D culture, Endo G expression increased in MCF-7 cells at 48 and 72nd hours, while it increased significantly in MDA-MB-231 cells at all hours. OSI results show that ROS production is increased in cell medium treated with AgNPs. In conclusion, AgNPs mediated by Phlomis armeniaca, synthesized by a green method, successfully induced damage to mitochondria, resulting in cell cycle arrest and consequent cell proliferation blockade and death in both MCF-7 and MDA-MB-231 cells.

Boric acid suppresses cell proliferation by TNF signaling pathway mediated apoptosis in SW-480 human colon cancer line.

BACKGROUND/AIM: Colon cancer is one of the most common cancers. Treatment success and survival rates are not high enough with current approaches. Therefore, there is a need to develop new agents and treatment methods. Boric acid is the most frequently observed form of boron. Some epidemiological data suggest that environmental exposure to boric acid reduces the incidence of prostate cancer in men, cervical and lung cancers in women. Experimental studies show, boric acid reduces cell proliferation and stimulates apoptosis in some prostate, melanoma, breast cancer cell lines. In this study, it was investigated whether boric acid could be a new candidate molecule that could be used in the treatment of colon cancer. MATERIALS AND METHODS: The effects of boric acid on human colon adenocarcinoma cell line SW-480 were investigated with BrdU, TUNEL, Caspase-3, and AIF immunohistochemical studies in both 2D and 3D culture systems. In addition, a qRT-PCR study was carried out to determine the expression changes in key genes that take part in apoptosis. RESULTS: We observed that boric acid suppresses cell proliferation and induces apoptosis both in 2D and 3D culture conditions. In addition, as a result of qRt-PCR studies, it was revealed that the observed apoptotic process was related to the TNF signaling pathway. CONCLUSION: Boric acid can be considered as a potential anti-cancer agent candidate for colon cancer treatment. DATA AVAILABILITY: All data generated or analyzed during this study are included in this published article.

Is Quercetin Beneficial for Colon Cancer? A Cell Culture Study, Using the Apoptosis Pathways.

BACKGROUND: Quercetin (QCT) is a dietary flavonoid with many beneficial effects (e.g., antioxidant, antiaging, antidiabetic, antifungal effects, and regulation of gastrointestinal motor activity in human); furthermore, it induces apoptosis, cell cycle arrest, and differentiation. OBJECTIVE: The apoptotic effects of OCT were investigated on SW480 human colon cancer cell lines in monolayer and spheroid cultures. METHODS: Quercetin (40-200 µM) was applied, and Inhibitory Concentration (IC50) doses were determined for three time intervals (24, 48, and 72 h). The effective dose was determined and applied for analyses, including staining with BrdU to investigate cell proliferation, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) to investigate apoptosis, and caspase-3 and Apoptosis Inducing Factor (AIF) to investigate caspase-dependent or independent apoptotic pathways. RESULTS: The effective dose of QCT was determined to be 200 µM and was found to induce apoptosis and inhibit cell proliferation at 24, 48, and 72 h,both in 2D and 3D cultures. Significant increases were observed in both caspase-3 and AIF staining, but cells showed greater caspase-3 staining compared with AIF staining at all time intervals (p<0.05). CONCLUSION: The QCT treatment groups showed more cell death and less cell growth compared with the untreated control groups in both 2D and 3D cultures of SW480 cell lines. The results suggest that quercetin induces apoptosis, inhibits cell proliferation, and has a protective role against colon cancer. However, further studies are needed to clarify its mechanism of action.

Curcumin induces apoptosis through caspase dependent pathway in human colon carcinoma cells.

BACKGROUND: We investigated the apoptotic effects of curcumin in the colon carcinoma cell line SW480. METHODS AND RESULTS: Cells were treated with 40-200 µM curcumin for 24, 48, and 72 h, and the IC50 values were determined for each time interval. BrdU, caspase-3, and TUNEL staining results and the gene expression of FADD, CASP8, and CASP3 were evaluated. Curcumin treatments significantly inhibited cell proliferation and significantly induced apoptosis for 24, 48, and 72 h. The proportion of BrdU-stained cells in the control groups were 58%, 57% and 61% and 28%, 27%, and 30% in the curcumin treatment groups at 24, 48, and 72 h, respectively. The proportion of apoptotic cells was 28%, 29%, and 28% in the control groups and 59%, 61%, and 60% in the curcumin treatment groups at 24, 48, and 72 h, respectively. As expected, caspase-3 staining also revealed a higher number of apoptotic cells in curcumin treatment groups at 24, 48, and 72 h compared to controls. The proportion of Caspase-3-stained cells in the control groups were 23%, 25%, and 24% and 59%, 60%, and 62% in the curcumin treatment groups at 24, 48, and 72 h, respectively. To prove caspase-3 staining results, FADD, CASP8, and CASP3 gene expressions were evaluated by real-time qPCR. Unlike the immunohistochemical results, no statistically significant upregulation was found at 24 and 48 h, while relative gene expressions of FADD, CASP8, and CASP3 was significantly upregulated at 72 h. The expression level increase was 0.88-, 1.19-, and 2.11-fold for FADD, 1.25-, 1.29-, and 1.59-fold for CASP8, and 1.33-, 1.46-, and 3.00-fold for CASP3 at 24, 48, and 72 h, respectively. CONCLUSIONS: These results suggest that curcumin may be a potential protective or treatment agent against colon cancer; however, further studies on curcumin-rich diets and curcumin bioavailability are required.

Secoisolariciresinol diglucoside induces caspase-3-mediated apoptosis in monolayer and spheroid cultures of human colon carcinoma cells.

Apoptotic effects of secoisolariciresinol diglucoside (SDG) in 2D and 3D cultures of SW480 cells were investigated. 40-200 µM SDG was used and IC50 values were determined for three different time intervals as 24, 48, or 72 hr for further experiments. BrdU, TUNEL, AIF, and caspase-3 stainings were used. SDG inhibited cell proliferation almost half and half for all time intervals in 2D and 3D cultures and also, induced apoptosis. Apoptotic cell percentages in the control group for 24, 48, and 72 hr were 27.00%, 29.00%, and 28.00%, respectively, while in the SDG treatment group were 59.00%, 61.00%, and 62.00%, respectively. In the spheroid cell culture, apoptotic cell percentages in the control group for 24, 48, and 72 hr were 6.90%, 7.20%, and 7.10%, respectively, while in the SDG treatment group were 19.50%, 19.50%, and 20.70%, respectively. Caspase-3 and AIF antibodies were used to indicate caspase-dependent and -independent apoptotic pathways. Significant increases were seen in both AIF and caspase-3 stainings when compared to the control group but caspase-3 staining results were significantly greater when compared to the AIF staining at all time intervals (p < .05). To prove this, CASP3 gene expression was evaluated by RT-qPCR. Unlike staining results, there was no statistically significant change at 24 hr in 2D and 3D cultures. But, significant upregulation at 48 (2.32-fold in 2D and 2.46-fold in 3D) and 72 hr (5.04-fold in 2D and 6.45-fold in 3D) were seen. PRACTICAL APPLICATIONS: Colon cancer is one of the most prevalent cancer in the developed countries and its etiology is complex. Although the underlying mechanisms are mostly unknown, the link between diet and colon cancer is known and dietary habits can promote cancer or protect against it. In recent years, flaxseed is accepted as a significant functional food ingredient and feeding with it could help in to prevent cancer. Secoisolariciresinol diglucoside is a flaxseed lignan and is metabolized to mammalian lignans by the gut. In the present study, SDG was evaluated for its apoptotic effects in colon carcinoma cell line via monolayer and spheroid cultures using immunohistochemical and gene expression techniques. Findings of this study suggest that SDG may protect against cancers and in particularly against colon cancer and further investigations has to be carried out for detailed underlying mechanisms.

The efficiency of vein viewing on pain and anxiety of children during peripheral cannula intervention: A randomized controlled study.

AIM: The purpose of this research is to estimate the efficiency of vein viewing device on 9-12 year-old children's pain and anxiety. METHODS: The research has been designed as an experimental study including pre-and post-test and control groups. Data were collected with personal information form, facial expressions rating scale, state anxiety scale, vein viewing device and a peripheral cannula. Both groups were applied to the state anxiety scale before and after the procedure while the facial expressions rating scale was applied during the procedure. RESULTS: Statistically significant difference was found between experimental and control groups regarding processing time, number of transaction attempts and facial expressions rating scale score averages. While there was no difference regarding the state anxiety scales average points of children in experimental and control groups before the procedure, a statistically significant difference was found in an advanced level regarding post-processing state anxiety levels. CONCLUSIONS: Usage of vein viewing device during peripheral cannula intervention reduces children's pain and anxiety levels and shortens the durations of the initiative.

Investigation of apoptotic effect of juglone on CCL-228-SW 480 colon cancer cell line.

BACKGROUND: Colon cancer is a major cause of morbidity and mortality in the world. Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim, and it has various pharmacological effects such as antiviral, antibacterial, and anticancer. In our study, we aimed to investigate the effect of juglone on CCL-228-SW 480 colon carcinoma cell line in monolayer and spheroid culture medium. MATERIALS AND METHODS: The CCL-228-SW 480 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. ID50 inhibition was determined on the dose for juglone and after it was found 20 µM was applied to the cells to examine the effect of juglone on CCL-228-SW 480 colon carcinoma cell line. After Juglone was applied the BrdU marking index, Transferase dUTP Nick ends Labeling (TUNEL) assay, active caspase-3 assay, apoptosis-inducing factor (AIF) assay were determined by immunohistochemistry in both the monolayer and spheroid cultures. RESULTS: The control group had a healthy pattern of S-phase fraction, and many of the CCL-228-SW 480 cells nuclei were observed to be positive for BrdU. Terminal Deoxynucleotidyl TUNEL-positive cells, active Caspase-3, and AIF were detected after treatment with juglone in both the monolayer and spheroid cultures. CONCLUSIONS: The dead cell count was higher in the CCL-228-SW 480 cell lines with juglone applied than in the controls. Juglone significantly inhibits the proliferation and induces the apoptosis of CCL-228-SW 480 cells in vitro.

Determination of Apoptotic Effect of Juglone on Human Bladder Cancer TCC-SUP and RT-4 Cells: An In Vitro Study.

This study aimed to investigate the effects of juglone on the human bladder carcinoma cell lines TCC-SUB and RT-4 in monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. The activity of caspase-3 was detected in vitro using a caspase-3 colorimetric assay kit according to the manufacturer's instructions. The bromodeoxyuridine (BrdU) labeling index was used to determine the cells of the synthesis phase. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay was used to determine the death of cells in both the monolayer and spheroid cultures. The control group had a large S-phase fraction and many of the TCC-SUB and RT-4 cells nuclei were observed to be positive for BrdU. The dead cell count was higher in the TCC-SUB and RT-4 cell lines with juglone applied than in the controls. We conclude that juglone significantly inhibits the proliferation and induces the apoptosis of TCC-SUB and RT-4 cells in vitro.

Effect of alpha lipoic acid on smoking-induced skin damage.

OBJECTIVE: Exposed to cigarette leads to the formation of reactive oxygen species and the generation of bioactive molecules that can damage skin cells. This investigation was carried out to study possible effects of Alpha Lipoic Acid (ALA) on smoking-induced rat skin injury. MATERIALS AND METHODS: 28 Spraque-Dawley female rats were allocated into three groups: control group (n = 8), smoking group (n = 10; 12 cigarettes/day, 8 weeks) and smoking + ALA group (n = 10; 12 cigarettes/day + 100 mg/kg, 8 weeks). Experiment group animals were sacrificed under anaesthesia with 10%ketamine + 2%xylasine at the end of second mounts and then skin examples were taken from the epigastric area. Histochemical (Haematoxylin-Eosin and Masson's trichrome, immunohistochemical (TNF-α) and biochemical analysis (CAT, MDA and protein carbonylation) were performed on these skin tissues. RESULTS: Histologically, skin was distinguished normal structure in the control group. In the smoking group, collagen bundles and hair follicle degradation/reduction, sweat gland degeneration, mononuclear cell infiltration in dermis were encountered. In ALA-treated group, all of these changes were improved (p < 0.05). Collagen bundles structures were appearance more regular than the smoking group . Immunohistologically, intense staining was observed in the smoking group, while very weak staining was observed in control group, weak staining was observed in the ALA-treated group. Biochemically; The CAT activity compared to cigarette group with control was raised high and in ALA group was higher compared to both groups, but not significant (p > 0.05). MDA; which is indicator of lipid peroxidation was significantly higher in cigarette group than in control group (p < 0.05) and was significantly lower in ALA group than cigarette (p < 0.05). Protein carbonylation was higher in cigarette group than the control group but not in the non-significant (p > 0.05). In the ALA it was significantly lower compared to the control group and cigarette (p < 0.05). CONCLUSIONS: Based on biochemical and histopathological determinations, the study showed that cigarette smoke can cause degenerative effects on skin tissues in rats. However, ALA has a curative effect on cigarette-induced injuries on the skin tissues by anti-oxidative and anti-inflammatory effects.

Determination of Spatial Distribution of Children Treated in Children Oncology Clinic with the Aid of Geographic Information Systems.

The main objective of this research is to examine child cancer cases in Zonguldak/Turkey descriptively in epidemiological aspect with the help of GIS. Universe of the study is composed of 60 children between 1 and 19 years old who were treated in Children Oncology Clinic with a diagnosis of cancer. Whole universe was reached without selecting a sample in the study. Data were collected by using a form prepared by obtaining expert advice and they were applied to children and their parents at study dates. Results were expressed as percentages. Chi-Square test was used in intergroup comparisons, results were assessed within 95 % confidence interval and p < 0.05 was considered as statistically significant. Variables that were used in the study were assessed, recorded in prepared data collection form and distribution maps were produced. When disease diagnosis of the children participated in the study were evaluated, the most observed three types are ALL with 33.3 % (n = 20), Medullablastoma with 13.3 % (n = 8) and Hodgkin-nonHodgkin Lymphoma with 11.7 % (n = 7). Kdz. Eregli with 31.7 % (n = 19), Center with 31.7 % (n = 19), and Caycuma with 18.3 % (n = 11) are the first-three counties where the cases were mostly observed. Statistically significant difference was found (p = 0.016) comparing disease diagnosis with living place, and distribution maps of the number of cancer cases were produced.

Effect of Curcumin on Systemic T Helper 17 Cell Response; Gingival Expressions of Interleukin-17 and Retinoic Acid Receptor-Related Orphan Receptor γt; and Alveolar Bone Loss in Experimental Periodontitis.

BACKGROUND: Curcumin has anti-inflammatory and antioxidant effects and is reported to have many biologic activities. The current study examines effect of curcumin on: 1) systemic T helper 17 (Th17) cell response; 2) gingival expressions of interleukin (IL)-17 and retinoic acid receptor-related orphan receptor (ROR) γt; and 3) alveolar bone loss (ABL) in experimental periodontitis. METHODS: Thirty-eight male albino Wistar rats were divided into four groups: 1) group 1 = periodontitis; 2) group 2 = periodontitis with curcumin treatment; 3) group 3 = periodontally healthy with curcumin treatment; and 4) group 4 = periodontally healthy. Curcumin was administered via oral gavage (30 mg/kg/d) for 15 days. After sacrifice via exsanguination, the following serum levels were determined using enzyme-linked immunosorbent assay: 1) IL-1ß; 2) IL-6; 3) IL-17A; 4) IL-23; and 5) transforming growth factor- ß. Morphometric evaluation of ABL was conducted and expression levels of IL-17 and RORγt in gingival tissues were evaluated immunohistochemically. RESULTS: Group 2 had significantly lower ABL than group 1 (P <0.0125). Highest expression levels of IL-17 and RORγt were observed in group 1 and were significantly higher than those in all other groups (P <0.0125). The only serum biochemical parameter significantly different among groups was level of IL-23 (P <0.05). Serum IL-23 levels were higher in groups 1 and 2 than groups 3 and 4 (P <0.0125); however, they were not significantly different for groups 1 and 2 (P >0.0125). CONCLUSION: Curcumin seems to be a promising host modulatory agent in periodontal disease pathogenesis regarding IL-17/IL-23 axis, with a decreasing effect on ABL and gingival expressions of IL-17 and RORγt.

Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity.

OBJECTIVES: Chronic consumption of high-fructose corn syrup (HFCS) causes several problems such as insulin resistance. The goal of the study was to investigate pancreatic damage induced by chronic HFCS consumption and the protective effects of alpha lipoic acid (ALA) on pancreatic cells. METHODS: Wistar Albino, 4-month-old, female rats weighing 250-300 g were randomly distributed into three groups, each containing eight rats. The study included an HFCS group, an HFCS + ALA-administered group and a control group (CON). The prepared 30% solution of HFCS (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks. ALA treatment was begun 4 weeks after the first HFCS administration (100 mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical dislocation 24 h after the last ALA administration. Blood samples for biochemical tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue samples for histopathological and immunohistochemical examinations (caspase-3, insulin and glucagon) were collected. RESULTS: Comparing the control and HFCS groups, serum glucose (150.92 ± 39.77 and 236.50 ± 18.28, respectively, p < 0.05), amylase (2165.00 ± 150.76 and 3027.66 ± 729.19, respectively, p < 0.01), lipase (5.58 ± 2.22 and 11.51 ± 2.74, respectively, p < 0.01) and pancreatic tissue MDA (0.0167 ± 0.004 and 0.0193 ± 0.006, respectively, p < 0.05) levels were increased, whereas tissue CAT (0.0924 ± 0.029 and 0.0359 ± 0.023, respectively, p < 0.05) activity decreased in the HFCS group significantly. Histopathological examination revealed degenerative and necrotic changes in Langerhans islet cells and slight inflammatory cell infiltration in pancreatic tissue in the HFCS group. Immunohistochemically there was a significant decrease in insulin (2.85 ± 0.37 and 0.87 ± 0.64, respectively, p < 0.001) and glucagon (2.71 ± 0.48 and 1.00 ± 0.75, respectively, p < 0.001) secreting cell scores, whereas a greater increase in caspase-3 (0.14 ± 0.37 and 1.00 ± 0.75, respectively, p < 0.05) expression was seen in this group compared with the controls. In the ALA-treated group, all of these pathologic conditions were improved. CONCLUSIONS: This study indicated HFCS induced pancreatic lesions, but ALA had ameliorative effects.

The effect of thermochemotherapy with mitomycin C on normal bladder urothelium, an experimental study.

PURPOSE: To investigate the effects of thermochemotherapy with mitomycin C (MMC) on normal rabbit bladder urothelium and to compare it with standard intravesical MMC and hyperthermia with normal saline. METHODS: Twenty-four male New Zealand rabbits, with a mean weight of 2.7 kg (in weight of 2.1­4.3 kg), were divided into three groups, each containing eight rabbits. Thermotherapy with only normal saline was performed in the first group, standard intravesical MMC was performed in the second group, and thermotherapy with MMC was performed in the last group. A week after the primary procedure, total cystectomy was performed and tissue samples were evaluated. RESULTS: The presence of epithelial vacuolar degeneration (p = 0.001), epithelial hyperplasia (p = 0.000), subepithelial fibrosis (p = 0.001) and hemorrhagic areas in the connective tissue (p = 0.002) was observed statistically significantly higher in the standard MMC group than in thermotherapy with normal saline group. There was almost a significant difference among standard MMC and normal saline group in terms of vascular congestion in the connective tissue (p = 0.08). Presence of epithelial vacuolar degeneration (p = 0.002), epithelial hyperplasia (p = 0.002), subepithelial fibrosis (p = 0.030), hemorrhagic areas (p = 0.011) and vascular congestion (p = 0.36) in the connective tissue was observed statistically significantly higher in the thermochemotherapy with MMC group than in standard intravesical MMC group. Polymorphonuclear cell infiltration was not considerable in any of the groups, and there was no significant difference between each groups (p = 0.140). CONCLUSION: Administration of intravesical MMC causes a toxic effect on the normal urothelium of the bladder rather than an inflammatory reaction. Heating MMC significantly increased this effect.

Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats.

The aim of the current study was to investigate the probable protective effects of Pentoxifylline (PTX) and Alpha Lipoic Acid (ALA), which display anti-oxidative efficacy against hepatotoxicity and nephrotoxicity, those being the major side effects of Methotrexate (MTX). Rats were divided into four groups: a control group; MTX (20mg/kg/day) group; MTX+PTX (20mg/kg/day+50mg/kg/day) group; and an MTX+ALA (20mg/kg/day+100mg/kg/day) group. At the end of the experiment, biochemical, histochemical and immunohistochemical analyses were performed on liver and kidney tissues of rats. We determined Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA), Nitric Oxide (NO) and Xanthine Oxidase (XO) levels in the liver and kidney. Moreover, Gamma Glutamyl Transferase (GGT), Direct Bilirubin (DBil), Blood Urea Nitrogen (BUN), and urea levels were measured in the serum. The histochemical evaluation revealed a significant decrease in MTX caused damage in the PTX- and ALA-treated groups (especially in ALA group). On the other hand, the immune staining of iNOS and TNF-α were observed most densely in the MTX group, while the density decreased in the PTX- and ALA-administered groups. We determined increased GGT, BUN, urea and levels of CAT, MDA, NO, and XO values in both groups, while GSH-Px (an increase in liver tissue) and DBil levels were decreased in the group that received MTX. However, we determined decreased SOD levels in liver tissue. In the PTX and ALA groups, the levels of GGT, BUN and urea as well as the levels of CAT, MDA, NO and XO decreased (SOD increased in the liver tissue), and the levels of GSH-Px and DBil increased. In conclusion, it can be stated that, although ALA is more effective in preventing the toxic effects of MTX on the liver and kidney, PTX also has a preventive effect. As a result, we can readily suggest that ALA and PTX can have protective effects by decreasing MDA, NO, BUN and urea values as antioxidants against MTX-induced damage in liver and kidney of rats.

The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity.

Amikacin (AK) is an antibacterial drug, but it has remarkable nephrotoxic and ototoxic side effects due to increase in reactive oxygen radicals. This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on AK-induced nephrotoxicity. Three different groups of rats (n = 6) were administered saline (control), AK (1.2 g/kg, intraperitoneally), ALA (100 mg/kg, p.o.) and AK combination (ALA one day before the AK for five days). Renal function, oxidative stress markers and histological changes were evaluated at the end of the experiment. Malondialdehyde was increased as an indicator of free radical formation in AK-induced group and decreased with ALA treatment. While catalase activity was increased significantly, superoxide dismutase and glutathione peroxidase activities were not statistically significant increased with ALA treatment. The result showed that AK enhanced levels of urea, creatinine and blood urea nitrogen in serum significantly. Administration of ALA reduced these levels of biochemical markers. Histopathological observations were confirmed by biochemical findings. In conclusion, ALA is suggested to be a potential candidate to ameliorate AK-induced nephrotoxicity.

Caffeic acid phenethyl ester protects against amphotericin B induced nephrotoxicity in rat model.

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 µmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 µmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models.

N-acetylcysteine modulates doxorubicin-induced oxidative stress and antioxidant vitamin concentrations in liver of rats.

Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress-induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N-acetylcysteine (NAC) relieves oxidative stress in DOX- induced liver injury in rat. Twenty-four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX+NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX+NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX+NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and ß-carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N-acetylcysteine induced modulator effects on the doxorubicin-induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels.

Effects of aspirin and nimesulide on tissue damage in diabetic rats.

This study was designed to compare the effect of Aspirin (AS) and Nimesulide (NM) on renal failure and vascular disorder in streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups; control, diabetic rats, diabetic rats plus AS and diabetic rats plus NM, which are COX inhibitors. The renal and aorta tissues morphology were investigated by light microscopy. Trunk blood was also obtained to determine plasma lipid peroxidation product malondialdehyde (MDA) and plasma activity of antioxidant enzymes. MDA levels were increased in the diabetic rats when compared to the control group. AS and NM administration caused a significant decrease in MDA production. Morphological damage in diabetic rats was severe in the kidney and in the aorta tissue. Treatment of AS reduced these damages, but NM did not exert positive effect on these damages in diabetic rats. As a result, although both AS and NM corrected lipid peroxidation parameters such as MDA via their antioxidant properties, only AS ameliorated pathological alteration in tissues. These findings indicate that there may be another mechanism in beneficial effect of AS in diabetic rats.