Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats.

Epilepsy is a chronic neurological disease that affects more than 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstay of treatment for most patients with epilepsy. However, AEDs have been reported to be associated with adverse cardiac effects. In this study, it was aimed to investigate the possible cardiac effects of low-dose (LD) and high-dose (HD) treatment of valproic acid (VPA) and lamotrigine (LTG), which are commonly used AEDs, in rats without epilepsy. Rats were randomly grouped as control, LD-VPA, HD-VPA, LD-LTG, and HD-LTG. The cardiac effects of AEDs were evaluated using immunohistological, biochemical, and hemodynamic parameters. A dose-dependent increase in the intensity of caspase-3 staining was detected in the VPA and LTG groups. The intensity of connexin-43 and troponin-T staining in the VPA groups and desmin staining in the LTG groups was significantly reduced. Biochemically, HD-VPA and HD-LTG administrations caused a significant increase in MDA level in myocardial tissue. In addition, as a result of hemodynamic evaluations, cardiac functions were found to be affected and blood pressure increased in HD-LTG group. The results of present study support that VPA and LTG treatment can increase cardiac risk markers.

Intracerebroventricular salusin-ß infusion to rats increases hypothalamus-pituitary-testicular axis hormones.

Salusin-ß (Sal-ß), which originates from preprosalusin, is a multifunctional hormone with a peptide structure. Sal-ß exists in the hypothalamus and can stimulate the pituitary gland. The present study was conducted to determine the effects of Sal-ß on hormones that play roles in the male reproductive system. Forty male Wistar Albino rats were used in the study. No infusions were performed on the control group, and infusions were applied to the infusion groups (artificial cerebrospinal fluid to the sham group, 2 and 20 nM Sal-ß to the experimental group) through intracerebroventricular infusion for 7 days at 10 µl/hour rate. The animals were decapitated after 7 days of infusion; and the hypothalamus, testicles, and blood tissue samples were collected. The gonadotropin-releasing hormone (GnRH) mRNA levels were determined from the hypothalamus tissues by using the Real Time-PCR Method, and the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were determined using the ELISA method. Also, Hematoxylin-Eosin Staining Method was used for histopathological evaluations in the testicle tissues. As a result, Sal-ß infusion increased GnRH mRNA levels in hypothalamus tissues (p < 0.05) besides, serum LH, FSH, and testosterone levels of the rats were higher at significant levels following Sal-ß infusion compared to the control and sham group (p < 0.05). In the histological examination of the testicle tissues, Sal-ß application was found to decrease the seminiferous tubule diameter and germinal epithelial thickness (p < 0.05). This evidence is the first, indicating that Sal-ß, which is administered to male rats with central infusion, stimulates hypothalamus and pituitary tissues, and causes increased secretion of male reproductive hormones.

Acute and Subacute Effects of Low Versus High Doses of Standardized Panax ginseng Extract on the Heart: An Experimental Study.

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Effects of ciprofloxacin and quercetin on fetal brain development: a biochemical and histopathological study.

PURPOSE: Teratogens cause birth defects and malformations while human development is being completed. In pregnancy, urinary tract infection (UTI) is a common health problem caused by bacteria. The fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin can treat various types of bacterial infections successfully. The aim of this study is to determine whether the use of ciprofloxacin during pregnancy causes oxidative stress on brain tissues of the fetus, and whether quercetin contributes to prevent this damage if stress has already occurred. MATERIALS AND METHODS: In our study, 22 young female Wistar albino rats weighing 250 g were used. Rats were mated overnight in separate plastic cages. Female rats were regarded as pregnant when a vaginal plug was observed, and these were divided into four groups of control, ciprofloxacin, quercetin, and cipro + quercetin. Two daily i.p. 20 mg/kg doses of ciprofloxacin were administered to ciprofloxacin group between 7 and 17 d of pregnancy. Throughout the study, daily (20 d) 20 mg/kg quercetin was dissolved in corn oil and administered to the quercetin group by oral gavage. Rats were fed ad libitum throughout the study. Fetuses were taken by C-section on the 20th day of pregnancy. Thereafter, the brain tissues were subjected to histological assessments and biochemical analyzes. RESULTS: The experimental groups were compared with the control group; ciprofloxacin affected fetal development, especially caused damage to neurons in brain tissue and cause hemorrhagic defects. And also, it was determined that many parameters were affected such as antioxidant parameters, enzyme levels and levels of malondialdehyde (MDA) (a marker of lipid peroxidation). Quercetin is a member of flavonoid with strong antioxidant properties, and our results indicate that the use of ciprofloxacin in pregnancy can result damage to fetal brain tissue. CONCLUSIONS: Unlike these results when some parameters are evaluated it is understood that this harmful effects suppressed by quercetin.

Maternal viral mimetic administration at the beginning of fetal hypothalamic nuclei development accelerates puberty in female rat offspring.

This study aimed to investigate the effects of maternal viral infection during a critical time window of fetal hypothalamic development on timing of puberty in the female offspring. For that purpose, a viral mimetic (i.e., synthetic double-strand RNA, namely, polyinosinic-polycytidylic acid, poly (I:C)) or saline was injected (i.p.) to the pregnant rats during the beginning (day 12 of pregnancy, n = 5 for each group) or at the end of this time window (day 14 of pregnancy, n = 5 for each group). Four study groups were formed from the female pups (n = 9-10 pups/group). Following weaning of pups, vaginal opening and vaginal smearing was studied daily until 2 sequential estrous cycles were observed. During the second diestrus phase, blood samples were taken for progesterone, leptin, corticosterone, follicle-stimulating hormone, and luteinizing hormone. Maternal poly (I:C) injection on day 12 of pregnancy increased body mass and reduced the time to puberty in the female offspring. Neither poly (I:C) nor timing of injection affected other parameters studied (p > 0.05). It has been shown for the first time that maternal viral infection during the beginning of fetal hypothalamic development might hasten puberty by increasing body mass in rat offspring.

Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats.

Preventive and/or therapeutic interventions for ischemic heart disease have gained considerable attention worldwide. We investigated the mechanism(s) underlying cardioprotection of apocynin (APO) and whether it attenuates isoproterenol (ISO)-induced myocardial damage in vivo. Thirty-two male Wistar Albino rats were randomised into four groups (n = 8 for each group): Group I (Control); Group II (ISO), ISO was given intraperitoneally (ip) (150 mg/kg/d) daily for 2 consecutive days; Group III (APO + ISO), APO was applied ip 20 mg/kg 30 min before the first ISO administration and continued for the next 2 d after the second ISO administration; Group IV (ISO + APO), after the ISO treatment on days 1 and 2, 20 mg/kg APO was given ip on days 3 and 4. Cardioprotective effects of APO were evaluated by biochemical values, histopathological observations and the antiapoptotic relative proteins. Mean blood pressure, heart rate, and electrocardiography (ECG) were also monitored. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), caspase-3 and connexin 43 levels were determined. Major ECG changes were observed in the ISO-treated rats. MDA, TOS, OSI and creatine kinase levels decreased and SOD, CAT, GSH and TAC levels increased, indicating that APO reduced cardiac injury and oxidative stress compared with controls. APO also decreased the number of cardiomyocytes with pyknotic nuclei, inflammatory cell infiltration, intracytoplasmic vacuolisation and myofibrils. APO provides preventive and therapeutic effects on ISO-induced myocardial injury in rats by inhibiting reactive oxygen species production, blocking inflammation and enhancing antioxidant status.

Effects of Molsidomine on Retinopathy and Oxidative Stress Induced by Radiotheraphy in Rat Eyes.

PURPOSE: To determine the role of Molsidomine in preventing radiation-induced retinopathy after head and neck region irradiation of rats with a single radiation dose of 15 Gy. MATERIALS AND METHODS: Male Wistar albino rats were randomly grouped into five as follows: (1) control group rats, which were applied through an intraperitoneal (i.p.) vehicle without radiotherapy (RT); (2) RT group rats received a single dose of 15 Gy irradiation and after daily 0.1 ml vehicle i.p. for 5 consecutive days; (3) molsidomine (MOL) group rats were treated for 5 consecutive days by i.p. with 4 mg/kg/day MOL; (4) irradiation plus MOL group (RT+MOL) rats received irradiation and after 10 days single daily i.p. dose of MOL for 5 consecutive days; and (5) MOL+RT group rats were treated for 5 consecutive days by i.p. with MOL before RT. At the end of the work the rats were sacrificed under high-dose anesthesia on the 16th day and then eye tissues were taken for histopathological, immunohistochemical (caspase-3), and biochemical analyses (superoxide dismutase [SOD], glutathione peroxidase [GSH], and malondialdehyde [MDA]). RESULTS: RT significantly decreased both the content of GSH and the activity of SOD, and significantly increased the production of MDA level in the rat eyes. MOL treatment significantly increased the SOD and GSH levels and significantly decreased the MDA production (p < 0.0001). In addition, RT significantly increased the number of ganglion cells (GCs; p = 0.001), whereas especially pretreatment with MOL improved (p = 0.013). RT led to significant retinopathy formation, and MOL therapy protected the retina from radiation-induced retinopathy (p < 0.0001). CONCLUSIONS: We suggest that MOL is a powerful antioxidant and free radical scavenger that prevents the rat eyes from radiation-induced retinopathy and oxidative stress.

Comparison of the Effects of Low-Level Laser Therapy and Ozone Therapy on Bone Healing.

This study aims to compare the effect of low-level laser therapy (LLLT) and ozone therapy on the bone healing. Thirty-six adult male Wistar albino rats were used for this study. Monocortical defects were shaped in right femur of all rats. Defects were filled with nano-hydroxyapatite graft. The animals were divided into 3 groups and each group was than divided into 2 subgroups. Then, LLLT with a diode laser was applied to the first group (G1), ozone therapy was applied to the second group (G2), and no treatment was applied to the third group as a control group (G3). Animals were sacrificed after 4th and 8th weeks and the sections were examined to evaluate the density of the inflammation, the formation of connective tissue, the osteogenic potential, and osteocalcin activity. As a result, there were no significant differences among the groups of 4 weeks in terms of new bone formation. In the immunohistochemical assessment, the number of osteocalcin-positive cells was higher in the laser group compared to the other group of 4 weeks; this difference was statistically significant in the LLLT and ozone groups (P < 0.05). Histomorphometric assessment showed that the new bone areas were higher in the LLLT and ozone groups; furthermore, there was a statistically significant difference in the LLLT in comparison with the control group at 8th week (P < 0.05). At the same time immunohistochemical assessment showed that osteocalcin-positive cells were considerably higher in G2 than G1 at 8th week (P < 0.05). The findings of this study may be the result of differences in the number of treatment sessions. Further studies are therefore needed to determine the optimal treatment modality.

The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney

This study was conducted to evaluate a possible protective role of apricot in apoptotic cell death induced by methotrexate (MTX) and renal damage by different histological and biochemical parameters. Twenty-eight rats were divided into four groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate induced renal failure, as shown by significant serum creatinine and urea elevation. Additionally, the results indicated that methotrexate significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, apricot significantly prevented toxic effects of methotrexate via increased catalase, superoxide dismutase, and glutathione levels but decreased formation of malondialdehyde. Also, it was determined that exposure to methotrexate leads to significant histological damage in kidney tissue such as glomerulosclerosis and apoptosis. On the other hand, these effects can be eliminated with apricot diet. These data indicate that apricot may be useful in preventing undesirable effects of MTX such as nephrotoxicity (AU)

Effects of ozone therapy on cyclophosphamide-induced urinary bladder toxicity in rats.

PURPOSE: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC). METHODS: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples. RESULTS: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05). CONCLUSION: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.

The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (IR) injury of the liver may cause various types of damage to hepatic tissues. It can affect the prognosis of patients and the success of an operation. Dexmedetomidine is a selective α2 receptor agonist. We investigated whether dexmedetomidine provides protection against IR-induced liver injury in rats. METHODS: Forty rats were divided equally into four groups. In group 1, the liver was manipulated after the laparotomy, and no occlusion of the vessels of the liver was performed. In group 2, once the abdomen was opened, 60 min of ischemia and 60 min of reperfusion were applied according to the segmental hepatic ischemia model. In group 3, 10 µg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. In group 4, 100 µg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. Further procedures in groups 3 and 4 were the same as those of group 2. After the experiment was completed, the rats were killed. Liver tissues were removed and stored until biochemical and histologic assessments were performed. RESULTS: The malondialdehyde level in group 2 was higher than that of groups 1, 3, and 4 (P = 0.001, P = 0.000, and P = 0.000, respectively). Superoxide dismutase, catalase, and glutathione levels in group 2 were lower than those in group 1 (P = 0.001, P = 0.027, and P = 0.014, respectively). Superoxide dismutase and catalase levels in group 4 were higher than those in group 2 (P = 0.002 and P = 0.000, respectively). GSH levels in groups 3 and 4 were higher than those in group 2 (P = 0.049 and P = 0.006, respectively). A lower glutathione peroxidase level was detected in groups 2 and 3 than that in group 1 (P = 000). Group 4 demonstrated an increase in glutathione peroxidase levels compared with group 3 (P = 0.014). The histologic injury scores in groups 2-4 were higher than those in group 1 (P = 0.003, P = 0.002, and P = 0.001, respectively). However, the histologic injury scores were lower in groups 3 and 4 than those in group 2 (P = 0.003 and P = 0.002, respectively). CONCLUSIONS: This study showed that dexmedetomidine may protect the liver against IR injury in rats.

Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for urinary tract infection: assessment of protective effects in a rat model.

OBJECTIVE: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. METHODS: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. RESULTS: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 × 10(3) cfu/mL) and chondroitin sulfate (1 × 10(4) cfu/mL) groups relative to the control group (5 × 10(4) cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 × 10(2) cfu/mL; P < 0.05). In the bladder tissues, statistically significant decreases in median bacterial growth rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium damage decreased in the treatment groups. However, this effect was prominent in hyaluronic acid + chondroitin sulfate group. CONCLUSION: Our experimental findings show that the hyaluronic acid + chondroitin sulfate combination has a potential benefit in reducing the bacterial load in urine and the thickness of the transitional epithelium.

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.

Protective effect of apricot (Prunus armeniaca L.) on hepatic steatosis and damage induced by carbon tetrachloride in Wistar rats.

The present study was planned to investigate the protective effect of 10 % and 20 % apricot-containing feed on carbon tetrachloride (CCl4)-induced hepatic steatosis and damage. Adult male Wistar rats (n 42) were divided into six groups of seven each, as follows: control group; CCl4 group; CCl4+10 % apricot group; CCl4+20 % apricot group; 10 % apricot group; 20 % apricot group. All apricot groups were fed with 10 % or 20 % apricot-containing feed for 5 months. CCl4 injections were applied to the CCl4 groups at the dose of 1 mg/kg for 3 d at the end of 5 months. In the CCl4 group, vacuolated hepatocytes and hepatic necrosis were seen, especially in the centrilobular area. Hepatocytes showed an oedematous cytoplasmic matrix, large lipid globules and degenerated organelles. The area of liver injury was found significantly decreased with apricot feeding. Malondialdehyde and total glutathione levels and catalase, superoxide dismutase and glutathione peroxidase activities were significantly changed in the CCl4 group and indicated increased oxidative stress. Apricot feeding decreased this oxidative stress and ameliorated histological damage. We concluded that apricot feeding had beneficial effects on CCl4-induced liver steatosis and damage probably due to its antioxidant nutrient (beta-carotene and vitamin) contents and high radical-scavenging capacity. Dietary intake of apricot can reduce the risk of liver steatosis and damage caused by free radicals.

Potent protective effect of apricot and beta-carotene on methotrexate-induced intestinal oxidative damage in rats.

Several studies have well confirmed the contribution of oxidative stress in the pathogenesis of methotrexate (MTX)-induced damage in the small intestine. Many agents have been tried experimentally to reduce or inhibit the oxidative stress. To our knowledge, there is no study about apricot consumption on the MTX-induced damage in the small intestine. The aim of this study was to determine the possible protective effects of apricot and beta-carotene on MTX-induced intestinal damage in rats. The rats were randomly divided into seven groups as follows; I-control group; II-apricot group; III-beta-carotene group; IV-MTX group; V-apricot+MTX group; VI-beta-carotene+MTX group and VII-apricot+beta-carotene+MTX group. In the MTX group; fusion and shortening in the villus, epithelial desquamation, crypt loss, inflammatory cell infiltration in the lamina propria, goblet cell depletion and microvillar damage were observed in the small intestine. Parallel to histological results, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were found to be increased, whereas superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP-x) activities and glutathione (GSH) content were decreased in the MTX group. However, single or combined application of apricot and beta-carotene ameliorated all of these hazardous effects in antioxidant system in MTX-treated groups. In conclusion, our results demonstrate that apricot and/or beta-carotene treatment may protect the impairment of oxidative stress and ameliorate MTX-induced intestine damage at biochemical and histological levels.

The effect of melatonin on 7,12-dimethyl-benz[a]anthracene injury in comparison with vitamin E + selenium in mouse kidneys.

The aims of this study were to observe the changes in antioxidative defense enzymes and renal morphology after 7,12-dimethyl-benz[a]anthracene (7,12-DMBA) administration in mice and to investigate the possible protective effects of melatonin against 7,12-DMBA-induced renal damage in comparison with vitamin E + selenium (vit E + Se). Forty female mice were divided into four groups: control, DMBA, DMBA + vit E + Se and DMBA + melatonin. In the DMBA group, mice were given injections of 7,12-DMBA (20 mg/kg). DMBA + vit E + Se group mice received injections of 7,12-DMBA + vit E + Se (20 mg/kg + 90 mg/kg + 1.8 microg/kg). In the melatonin group, mice were given injections of 7,12-DMBA + melatonin (20 mg/kg + 4.2 mg/kg). The experiment lasted for 21 days. Mice were killed and the kidneys were taken for enzyme analyses and histologic examination. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities were found significantly decreased in the DMBA group and in the DMBA + vit E + Se group when compared with the control group (P < 0.05), whereas CAT and GSH-Px activities were found significantly elevated in the DMBA + melatonin group when compared with the control (P < 0.05) and the DMBA group (P < 0.01). Exposure to DMBA resulted in tubular alterations in renal cortex. Morphometric analysis revealed proximal and distal tubular damage (P < 0.05). These alterations were found to be prevented by melatonin but not with vit E + Se administration. These results reveal that melatonin stimulates CAT and GSH-Px activities and prevents renal injury better than vit E + Se combination in mice kidneys.