Montelukast Influence on Lung in Experimental Diabetes.

Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.

Montelukast influence on kidney in experimental induced diabetes mellitus.

Leukotrienes are important icosanoids group involved in a lot of normal and pathological states. Montelukast (MK) is a selective cysteinyl leukotriene receptor (Cys LT1) antagonist. Purpose. The purpose of the study is to observe the influence of MK on renal damage caused by experimental diabetes in rats. The experiment was carried out on four groups of adult male Wistar rats. Lot I was a witness and received 1.5ml of physiological saline ip. in unique dose on the first day of the experiment. Lots II and III have been caused experimental diabetes by streptozotocin (STZ) administration of 60mg/kg ip. in the unique dose. Lot III also received MK daily 10mg/kg/day daily 8weeks.Lot IV received only MK 10mg/kg/day daily 8 weeks. After eight weeks all animals were anesthetized and were sacrificed. The following pathological modifications were observed: tubular injury, glomerular hypertrophy and lesions, leukocytes infiltration. Obtained data showed that MK has significantly reduced the intensity of glomerular lesions (score 3.50+/-0.21 in STZ lot vs. 2.50+/-0.17 in STZ+MK lot p<0.01) and tubular damages. Renal interstitial leukocyte infiltration in animals with diabetes has been also reduced by MK. MK has a partially protective action against the lesions produced by experimental diabetes.

Changes in Some Divalent Cations Concentrations In An Experimental Rat Model of Gentamicin-Induced Acute Renal Failure.

Aim: The changes in divalent cations concentration were assessed in and experimentally gentamicin-induced renal failure in white Wistar rats. Material and Methods: The white male Wistar rats were distributed into 4 groups of 7 animals each and were treated intraperitoneally as follows: Group I (Control): distilled water in a volume of 0.5ml/100g rat/day for10 days; Group II (Ge): gentamicin 80 mg/kbw/day for 7 days; Group III (Ge+Zn): gentamicin 80 mg/kbw/day for 7 days and ZnCl2 5 mg/kbw/day for 10 days prior to administration of Ge and then another 7 days simultaneously with Ge administration; Group IV (Zn): ZnCl2 5 mg/kbw/day for 17 days. Before starting the experiment (I0) and at 3, 7 and 10 days after the first Ge administration, magnesium, copper and zinc plasma concentrations and urinary magnesium levels were determined. Results: Zn administration significantly decreased (p<0.001) plasma Mg concentrations in Ge+Zn group compared to Ge group after 7 days in the experiment, and induced a lower urinary elimination of Mg in Ge+Zn group (p<0.05) than in Ge group (p<0.01). Also, Zn induced a slight augmentation of Cu concentration in Ge+Zn group (p<0.05) compared to Ge group after 7 and 10 days. Conclusions: The variation in divalent cation concentrations in the context of renal diseases may be helpful for an early diagnosis and effective alternative therapeutic measures.

Protective effect of magnesium and metformin on endometrium and ovary in experimental diabetes mellitus.

We evaluated the effect of magnesium and metformin on streptozotocin (STZ)-induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised four groups, each consisting of eight, non-pregnant, adult Wistar female rats with a weight range of 170-250 g, maintained under the usual laboratory conditions. One group of female rats was the control group that received no treatment. To induce DM, the other three groups of animals received streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group received no additional treatment. The second group received MgCl2 1 mmol/kg/day i.p. daily, for eight weeks. The third group received daily metformin, 100 mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total plasma magnesium concentrations, and oxidative status were determined prior to, 24 hours and eight weeks after administration of the STZ. After eight weeks of treatment, the animals were anesthetized and sacrificed. The uterus and ovaries were removed and examined under optical microscopy. The data obtained were analyzed statistically using the ANOVA test. The results showed that the number of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group compared to the control group (p<0.01). The number of atretic follicles found in the group receiving daily MgCl2 was 32% higher compared to the untreated control group (p<0.05). The number of atretic follicles was increased by only 27% in the metformin-treated group, as compared with the untreated control group.. The STZ-induced diabetes group presented an endometrial epithelial atrophy not seen in the control group. MgCl2 administration attenuated the degree of endometrial atrophy, there being an endometrial epithelial thickness of 19.43 ± 0.51 µm in the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 ± 0.27 µm in the STZ only-treated diabetic group.

The effect of pioglitazone on non-pregnant female genital tract in experimental diabetes mellitus.

UNLABELLED: The effects of pioglitazone, a very used drug in the treatment of non-insulin dependent diabetes mellitus, were tested at the level of ovary of non-pregnant female rats. MATERIAL AND METHODS: The experiment was performed on three groups of adult non-pregnant female rats. group 1 was a control group (and did not receive any substance), group 2 received streptozotocin 60 mg/kg i.p. (single administration), and group 3 received streptozotocin 60 mg/kg i.p. (single administration) and pioglitazone 5 mg/kg/day p.o., daily for 8 weeks. The plasma glucose, cholesterol and triglyceride levels were determined before drugs administration and during the experiment. After 8 weeks the animals were anesthetized and sacrificed. The ovaries were examined by optical microscopy. A morphometric evaluation was performed. The obtained data were statistically interpreted by ANOVA test. RESULTS: After 8 weeks of treatment the plasma glucose and triglyceride levels were significantly lower in the pioglitazone treated group compared to the streptozotocin only group. In the pioglitazone group the number of primordial and primary ovarian follicles was significantly higher than in streptozotocin only group. CONCLUSIONS: The results showed a partial protective action of pioglitazone on ovary in nonpregnant diabetic female rats.

The influence of oral steroidal contraceptives on magnesium concentration in breast milk.

This study determined the total magnesium concentration in the breast milk of mothers that were using oral, steroidal contraceptives during lactation. The study involved two groups of breast-feeding mothers that were receiving oral contraception, and a control group of 15 breast-feeding mothers that did not receive oral contraception. The first group received a daily combination pill (levonorgestrel 0.15 mg + ethinylestradiol 0.03 mg); the second group received a daily mini-pill (progestin-only pill, containing norethindrone 0.35 mg). The total magnesium concentrations of plasma and breast milk were determined before the start of contraception and after 30 days of contraception. The results showed that after 30 days of contraception, the contraceptive drugs had not significantly modified the total breast milk magnesium concentration (1.16 ± 0.11 mmol/L before treatment versus 1.01 ± 0.12 mmol/L, in first group; 0.97 ± 0.16 mmol/L before contraception versus 1.08 ± 0.11 mmol/L, in the second group). There were no significant changes in the total magnesium concentration in the breast milk of the control group after the 30 days. In addition, the oral, steroidal contraceptives (pill and mini-pill) did not affect the total magnesium concentration in the plasma of lactating mothers.

Influence of therapy with metformin on the concentration of certain divalent cations in patients with non-insulin-dependent diabetes mellitus.

Research was performed on a group of 30 patients with non-insulin-dependent diabetes mellitus (NIDDM), who never received antidiabetic medication before, and on a group of 17 healthy adults. The patients were administered treatment with metformin, 1,000 mg/day. Plasmatic and urinary concentration of magnesium have been measured, copper and zinc along with the concentrations of glucose, HDL, LDL, cholesterol, tryglicerides, HbA1c, and total erythrocyte magnesium, in advance and after 3 months of treatment. Data showed significant differences in the NIDDM group vs the control group: for plasma magnesium-1.95 ± 0.19 vs 2.20 ± 0.18 mg/dl, p < 0.001; urine magnesium-237.28 ± 34.51 vs 126.25 ± 38.22 mg/24 h, p < 0.001; erythrocyte magnesium-5.09 ± 0.63 vs 6.38 ± 0.75 mg/dl, p < 0.001; plasma zinc-67.56 ± 6.21 vs 98.41 ± 20.47 µg/dl, p < 0.001; urine zinc-1,347.54 ± 158.24 vs 851.65 ± 209.75 µg/24 h, p < 0.001; plasma copper-111.91 ± 20.98 vs 96.33 ± 8.56 µg/dl, p < 0.001; and urine copper-51.70 ± 23.79 vs 36.00 ± 11.70 µg/24 h, p < 0.05. Treatment with metformin for 3 months modified significant erythrocyte magnesium-5.75 ± 0.61 vs 5.09 ± 0.63 mg/dl, p < 0.001 and urine magnesium-198.27 ± 27.07 vs 237.28 ± 34.51 mg/24 h, p < 0.001, whereas it did not modify significant the plasmatic and urinary concentration of the other cations. The erythrocyte magnesium concentration was inversely correlated with HbA1c (r = -0.438, p = 0.015). The plasma level of copper was positively correlated with HbA1c (r = 0.517, p < 0.003), tryglicerides (r = 0.534, p < 0.003), and cholesterol (r = 0.440, p < 0.05), and the plasma level of zinc was inversely correlated with glycemia (r = -0.399, p = 0.029). Our data show a significant action of metformin therapy, by increasing the total intraerythrocyte magnesium concentration and decreasing the urinary magnesium elimination, positively correlated with the decrease of glycemia and HbA1c in NIDDM patients.

Pharmacological agents that affect sperm motility.

UNLABELLED: Male fertility is determined by several factors one of which is essential sperm motility. A large number of drugs have a toxic influence on sperm motility MATERIAL AND METHODS: We tested the influence of some antibacterial antibiotics on rat sperm motility. Following antibiotics were tested antibacterial influences: amoxicillin + clavulanic acid dose of 30 mg/kg body/day, daily and that 150 mg/kgbody/day, daily, respectively ceftazidime dose of 50 mg/kgbody/day, daily and that 250 mg/kgbody/day, daily. For each antibiotic and dose was used by a group of rats that received treatment for 12 days for amoxicillin+clavulanic acid and 11 days, respectively 10 days for ceftazidime. A control group of rats was not received and no substance Sperm motility was determined and histopathological examination of tissues was performed harvested. RESULTS: Our data showed that the combination of amoxicillin-clavulanic acid in doses of 30 mg/kgbody/day (dose is reached in clinical practice) of sperm motility reduced with 49.33% (p<0.01) and dose of 150 mg/kgbody/day, sperm motility was reduced with 68.96% (p<0.01) ceftazidime doses tested significantly reduced motility of sperm (p<0.01), dose of 50 mg/kgbody/day, sperm motility was reduced with 83.79% and dose of 250 mg/kgbody/day, sperm motility was reduced with 85.36% (p<0.01). CONCLUSIONS: Ceftazidim has a strong effect on sperm cells motility at therapeutic doses. This effect is higher compared to amoxicillin+clavulanic acid association.

Research on serum and saliva concentration of some bivalent cations in patient with suppurations of the oro-maxillo-facial area.

UNLABELLED: Bivalent cations, such as calcium, magnesium, zinc, copper and manganese play important roles in some physiological and pathological processes on the human body. AIM: To determine possible modifications in serum and saliva concentration of total-Ca2+, total-Mg2+, Zn2+ and Cu2+ in patients with suppurative infections of the oro-maxillo-facial area and eventually their significance for the mentioned pathology. MATERIAL AND METHOD: Study included 47 patients with suppurative infections of the oro-maxillo-facial area, hospitalised during 2006-2008 in the oro-maxillo-facial clinic of "Sfântul Spiridon" Hospital Iasi and 43 healthy control volunteers. RESULTS: Results revealed decreased serum Zn2+ (0.94 +/- 0.21 vs. 1.39 +/- 0.14 mg/L, p < 0.01), decreased serum Zn2+/Cu2+ ratio and increased serum and saliva total-Mg2+ concentration (27.34 +/- 2.61 mg/mL in patients vs. 23.83 +/- 1.61 mg/L in healthy controls- serum, p < 0.05 and 3.79 +/- 0.41 mg/mL in patients vs. 3.21 +/- 0.40 mg/mL in healthy controls - saliva, p < 0.05) in patients with suppurative infections of the oro-maxillo-facial area vs. healthy controls. There were no statistically significant differences in total-Ca2+ concentrations in saliva and serum. Our data are in agreement with medical literature revealing zinc deficiency as a predisposition factor to infection. CONCLUSION: We consider that a significant increase in total-Mg2+ saliva concentration, as well as a decrease in Zn2+/Cu2+ serum ratio could be considered a marker for predisposition to oro-maxillar suppurations.