Nihat Ekinci

Beneficial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study.

The effects of montelukast against methotrexate-induced liver damage were investigated. 35 Wistar albino female rats were divided into 5 groups as follows: group I: control; group II: montelukast (ML); group III: methotrexate (Mtx); group IV: montelukast treatment after methotrexate application (Mtx + ML); group V: montelukast treatment before methotrexate application (ML + Mtx). At the end of the experiment, the liver tissues of rats were removed. Malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione levels were determined from liver tissues. In addition, the liver tissues were examined histologically. MDA and MPO levels of Mtx group were significantly increased when compared to control group. In Mtx + ML group, these parameters were decreased as compared to Mtx group. Mtx injection exhibited major histological alterations such as eosinophilic staining and swelling of hepatocytes. The glycogen storage in hepatocytes was observed as decreased by periodic acid schiff staining in Mtx group as compared to controls. ML treatment did not completely ameliorate the lesions and milder degenerative alterations as loss of the glycogen content was still present. It was showed that montelukast treatment after methotrexate application could reduce methotrexate-induced experimental liver damage.

Beneficial Effects of Montelukast against Cisplatin-Induced Acute Renal Damage in Rats

Objective: In this study, the therapeutic and protective effects of montelukast against cisplatin (CP)-induced acute renal damage were investigated. Materials and Methods: Thirty-five female rats were divided into five groups as follows: (1) control, (2) montelukast (10 mg/kg daily for 10 days per-oral (p.o.), (3) CP (single dose 7 mg/kg intraperitoneally (i.p.)), (4) CP + montelukast (10 mg/kg daily for 10 days p.o., after 3 days of the injection of CP), (5) montelukast (10 mg/kg daily for 10 days p.o.) + CP (single dose 7 mg/kg i.p., after the last dose of montelukast). At the end of the experiment, malondialdehyde (MDA), a lipid peroxidation product, myeloperoxidase (MPO), and reduced glutathione (GSH) levels were determined in the renal tissue. Also, blood urea nitrogen (BUN) and creatinine (Cr) levels were assayed from the trunk blood samples. Results: CP treatment caused a significant elevation of MDA, MPO, BUN, and Cr levels when compared with the control group. Also, GSH levels were found to be reduced due to the CP treatment. Montelukast administration after CP injection ameliorated all of these parameters. Our histopathological findings (marked swelling of epithelial cells, tubular dilatation, tubular desquamation, and loss of brush border in the kidney) were consistent with the biochemical results. Conclusion: Montelukast treatment after CP injection exerted therapeutic effects against CP-induced acute kidney damage.

Effects of intraperitoneal administration of the phenytoin on the skeletal system of rat fetus

This study was conducted on determining the effects of phenytoin on the skeletal system of the fetuses of 13 Wistar Albino rats. The female rats were divided into two groups after the vaginal smear test: the group 1 (control group) included 6 individuals, whereas the group 2 (phenytoin group) comprised 7 animals. A dose of 25mg/kg/day phenytoin was administered intraperitoneally to pregnant rats on the 8th-10th days of pregnancy and fetuses were obtained by C-section on the 20th day. A number of 82 fetuses were observed by double staining technique. Their lengths and weights were measured, revealing the statistically significant differences between the two groups (p<0.001). The lengths of the fetuses in the group 2 were determined as to be 14% shorter and the weights 13% lower compared to those in the group 1. Similarly, number of the fetuses obtained in one gestation decreased 9% in the group 2. Ossification of the skull bones in the fetuses of the group 2 was observed eminently to be deteriorated through using dissection microscope and inspection. Costal separation anomaly was observed in the 10 fetuses of the group 2. The separated-laterally located costal components were not attached to the costal arch. Shape malformations in the last two ribs and wide angularity, particularly in the last six ribs, were also determined. This study has documented that intraperitoneal usage of the pheytoin during pregnancy may cause to different skeletal malformations, even with lower doses, in rat fetuses.

Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice

Antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. Human plasminogen-derived angiostatin K1-3 is one of the most potent antiangiogenic agents known currently. However, it is unclear whether angiostatin has got protective effects on colon cancer. So we investigated the protective effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in mice. Thirty Balb/C male mice, weighing 25–30 g and 8 weeks of age, were used. Twenty of the mice were treated with DMH subcutaneously (20 mg/kg) once a week for 12 weeks. Six mice died during the DMH injection and surviving mice were divided into two groups (7 mice in DMH and 7 mice in DMH + angiostatin groups). In the angiostatin group, 6 weeks after the last DMH injection the animals were first treated with angiostatin (20 μg/mouse) intraperitoneally and then subcutaneously every 48 h (5 μg/mouse) throughout a period of 12 weeks. The animals were killed after 30 weeks for histopathological examination. When we look at the distribution of lesions in the colon, they mainly occurred in the distal colon. The incidence of mean colonic lesions in a tumor-bearing mouse was 9.85 ± 4.91 in those treated with DMH and 8.71 ± 3.49 in those treated with angiostatin. The incidence of colon tumors was not significantly affected by low dose of angiostatin, and we noticed that the number of lesions decreased by 12% in DMH + angiostatin group compared to the number of the lesions in DMH group, but this decrease was not statistically significant (p > 0.05). The administration period of angiostatin corresponds to the precancerous period and the reduction in the number of lesions could be important for the protective function of angiostatin in DMH + angiostain group. We assume that therapeutic effects of angiostatin are related to its doses, route of administration, frequency and administration period. In addition, we believe that combination of high doses of angiostatin with radiation, gene therapy or chemotherapy might be successful in proper tumor model.

The role of chrysin against harmful effects of formaldehyde exposure on the morphology of rat fetus liver and kidney development

This study was aimed to investigate possible harmful effects of formaldehyde (FA) exposure on the morphology of fetus liver and kidney development during pregnancy and also to determinate possible protective role of chrysin (CH) against these harmful effects. For this aim, after pregnancy was induced, 58 female rats were divided into 6 groups. Serum physiologic (SF) was injected to the Group I rats intraperitoneally (i.p.). 20 mg/kg CH was given to the Group II via gavage. 0.1 mg/kg FA was applied to the Group III (i.p.), 1 mg/kg FA was injected to Group IV (i.p.) 0.1 mg/kg FA was given to Group V i.p., and 20 mg/kg CH was given to the same group via gavage. 1 mg/kg FA was applied to Group VI i.p., and 20 mg/kg CH was given to the same group via gavage. Fetuses were taken from each pregnant rat with cesarean section on the 20th day of the pregnancy. The morphological analyses of the fetuses, liver and kidney; biochemical and histological analyses of the liver and kidney were performed. The fetal body, liver and kidney weight of the FA groups demonstrated a statistically significant decrease the compared to control group. Also the FA-1 group were observed histopathological changes on the fetus liver and kidneys. FA exposure causes harmful effects on fetus the liver and kidneys. CH reduces the negative effect on morphological variables statistically. Although CH is insufficient to fix the histopathological changes that occur in the liver, damaging effects that occur in the kidney decreased statistically.

Lamotrigin kullanan epileptik ratların yeni doğan yavrularının karaciğerlerinde oksidatif hasarın incelenmesi

Bu calismada amacimiz epilepsi tedavisinde sikca kullanilan antiepileptik ilaclardan lamotirijinin yalniz veya folik asit ile birlikte gebelikte kullaniminin yeni dogan yavrularin karacigerlerinde oksidatif stres parametreleri uzerine etkilerini arastirmaktir. Calismamiz 170-250 gr agirliginda 10 adet eriskin disi Wistaralbino turu rat ve bunlardan dogan 20 yavru rat ile yapildi. Ratlar; Gebe ratlar kontrol grubu, deneysel epilepsi grubu, lamotrijin grubu, lamotrijin+deneysel epilepsi grubu ve lamotrijin epilepsi+folik asit olarak bes gruba ayrildi. Gebeligin 13. Gununde gebe ratlara deneysel penisilin akut epilepsi modeli olusturuldu. Lamotrijin grubuna gebeligin ilk gununden itibaren her gun intraperitoneal enjeksiyon ile 25mg/gun dozunda lamotrijin verildi. Lamotrijin+folik asit grubuna her gun intraperitoneal enjeksiyon ile 25mg/gun dozunda lamotrijin ve 400µg/kg folik asit verildi. Daha sonra gebe ratlarin dogum yapmalari beklendi. Dogumdan hemen sonra yeni dogan ratlarin karacigerlerinde glutatyon, malondialdehit, glutatyon peroksidaz ve superoksid dismutaz seviyeleri spektrofotometrik olarak olculdu. Lamotrijin ve lamotrijin+epilepsi gruplarina ait biyokimyasal degerler incelendiginde, karaciger malondialdehit anlamli bir sekilde yukseldigi, glutatyon peroksidaz enzim aktivasyonlarinin kontrol grubuna gore istatistiksel olarak anlamli azalmis oldugu goruldu. Folik asit ile birlikte lamotrijin verilen grupta, karaciger doku orneklerine ait malondialdehit duzeylerinin anlamli azaldigi, glutatyon ve glutatyon peroksidaz duzeyinin arttigi tespit edildi. Gebe ratlar uzerinde gerceklestirmis oldugumuz bu calismada, lamotrijin kullaniminin yeni dogan yavrularin karacigerlerinde erken donemde bir oksidatif hasar meydana getirebilecegi ancak meydana gelen oksidatif doku hasarinin folik asit kullanildiginda engellendigi biyokimyasal olarak ortaya kondu