Protective effects of molsidomine against doxorubicin-induced renal damage in rats.

PURPOSE: The purpose of this study was to investigate the therapeutic and protective effects of molsidomine (MLS) against doxorubicin (DOX)-induced renal damage in rats. METHODS: Forty rats were randomly divided into five groups (control, MLS, DOX, DOX+MLS and MLS+DOX groups). Thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO) and glutathione peroxidase (GPx) levels were determined from kidney tissues and blood urea nitrogen (BUN), creatinine (Cr) and albumin (Alb) levels also determined. RESULTS: DOX treatment caused a significant increase in TBARS levels and a significant decrease in the GSH and CAT levels compared with the control group. In comparison, MLS administration before DOX injection caused a significant decrease in TBARS levels and also increases in GSH and CAT levels, whereas treatment of MLS after DOX injection did not show any beneficial effect on these parameters. All groups showed a significant increase in NO levels compared to the control group. There were no significant differences among the all groups for BUN and Cr levels. Serum level of Alb decreased in the DOX-treated groups when compared with control and MLS groups. The histopathological findings were in accordance with the biochemical results. MLS treatment reversed the DOX-induced kidney damage in group 4. MLS treatment before DOX injection exerted a protective effect against DOX-induced kidney damage. CONCLUSIONS: MLS shows promise as a possible therapeutic intervention for the prevention of kidney injury associated with DOX treatment. Additional studies are warranted.

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.

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.

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.

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.

Volumetric evaluation of the relations among the cerebrum, cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging.

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm3 in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm3 in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm3 in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm3 in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.

Relation between intracranial volume and the surface area of the foramen magnum.

Several investigators have estimated the intracranial volume (ICV) in the past which indirectly reflects the brain volume. Most of these studies have been made on the dry skulls using linear dimensions, packing methods or occasionally radiological methods. It is also reported that the etiology of cerebellar tonsillar herniation is closely related to the size of the foramen magnum (FM). In the present study the ICVs have been estimated in 28 dry skulls using filling water method and the surface area of FMs were measured planimetry method. The estimated mean ICV was 1,311 +/- 133 cm. Surface area of FM was 760 +/- 144 mm. Antero-posterior and lateral direct roentgenograms of the skulls were also taken and the width, height and length (WHL) of the skull were measured by means of the cephalometry on radiograms. The relationship between the ICV, WHL and surface area of FM were analyzed statistically. The ICV, WHL and surface area of FM was correlated well (r = 0.271, P < 0.005; r = 0.265, P < 0.005, respectively) and a regression formula was proposed. Our results showed that skulls with larger ICV and WHL have larger FM surface area. We also suggested a regression formula that could be used to predict the surface area of FM regarding to the ICV and WHL values. In the next step, we took roentgenograms of skulls and obtain ICV measuring the width, length and height of skulls by means of cephalometry and investigate the relation between the findings of cephalometry and surface area of FM. The cephalometry could apply on living subjects and, thereby, our findings could provide some data to evaluate the etiology of Arnold Chiari malformation and achondroplasia for living subjects.