Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage.

Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant­antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague­Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.

The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes.

In this present study, the duration of melatonin (Mel) administered to diabetic rats was prolonged so as to examine its effects on the biochemical liver parameters of diabetic rats. In the experiment, Male Sprague Dawley rats were divided randomly into five groups; the control, diabetic + Mel, diabetic, diabetic + insulin, and diabetic + Mel + insulin. Diabetes mellitus was induced by administration of a single dose of streptozotocin (60 mg/kg) intraperitoneally and rats were given vehicle as a solvent for Mel every day for 12 weeks. In the diabetic + Mel group, diabetic rats were administered Mel (10 mg/kg/day) for 12 weeks to treat diabetes. The diabetic + insulin group were diabetic rats given insulin (6 U/kg) subcutaneously for 12 weeks. The diabetic + Mel + insulin rats received insulin and Mel at the same dose and time. At the end of the experiment, the animals were decapitated and liver tissues were taken. The protective effect of Mel on liver tissue of diabetic rats was investigated, total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, adenosine deaminase, xanthine oxidase, paraoxonase 1, sodium/potassium ATPase, myeloperoxidase, γ-glutamyl transferase, sorbitol dehydrogenase, tumor necrosis factor-alpha, homocysteine, nitric oxide, glucose-6-phosphate dehydrogenase, and glycoprotein levels were determined in liver tissues. Treatment with Mel and/or insulin has been found to have a protective effect on biochemical parameters. The results showed that administration of Mel to diabetic rats prevented the distortion of the studied biochemical parameters of liver tissues.

Petroselinum crispum Extract Prevents Scopolamine-Induced Lens Damage in Rats.

Alzheimer's disease (AD) is a neurodegenerative disease that occurs especially in advanced ages. It reduces the quality of life of both the patient and their relatives. In addition to its primary effects, AD causes metabolic defects and tissues are damaged due to these effects. Oxidative stress damages cells by disrupting antioxidant/oxidant balance in many tissues, especially due to AD. In individuals with AD and the elderly, lens tissue is damaged due to oxidative stress and may cause vision loss. Therefore, it is very important to investigate herbal products that both prevent/cure AD and reduce AD-related oxidative stress, as they may have fewer side effects. In this study, the protective effects of parsley (Petroselinum crispum) extract on lens tissues of an experimental AD model induced by scopolamine were examined and evaluated through biochemical parameters. The result of biochemical experiments and principal component analysis, was observed that parsley extract had a therapeutic effect by reducing oxidative stress in lens tissues of experimentally induced AD rats. It can be suggested that the phenolic and flavonoid-rich content of parsley extract may have caused the reduction of oxidative damage in lens tissues and can be used to protect lens tissue against oxidative stress due to AD disease.

A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.), also called Turkish oregano, is a perennial and herbaceous plant species grown for centuries for medicinal, cosmetic and culinary purposes. This is the first study to investigate the putative neuroprotective and pro-cognitive activities of O. onites essential oil (OOEO) against scopolamine-induced amnesia of AD-type in Wistar albino rats. The results of behavioral tests revealed that OOEO administration was able to significantly alleviate learning and memory impairments induced by scopolamine in vivo. The observed effects could be attributed to inhibition of acetylcholinesterase activity, attenuation of oxidative stress and prevention of neuronal apoptosis in the hippocampus and frontal cortex of AD rats. Modulation of pro-inflammatory enzymes, including cyclooxygenase-2, inducible nitric oxide synthase and myeloperoxidase, might further contribute to the neuroprotective properties of OEOO, as predicted by our in silico models. These findings offer novel insights into the therapeutic potential of OEOO in patients with AD.

Exercise improves testicular morphology and oxidative stress parameters in rats with testicular damage induced by a high-fat diet.

Obesity and male infertility are problems that affect population. Exercise is a nonpharmacological way to reduce the negative health effects of obesity. The purpose of this study was to examine the effects of exercise on hormone levels, blood-testis barrier, and inflammatory and oxidative biomarkers in rats that became obese due to a high-fat diet (HFD). Male rats received a standard diet (STD group) or a HFD (HFD group) for 18 weeks. During the final 6 weeks of the experiment, swimming exercises (1 h/5 days/week) were given to half of these animals (STD + EXC and HFD + EXC groups). Finally, blood and testicular tissues were analysed by biochemical and histological methods. Body weight, leptin, malondialdehyde, interleukin-6, TNF-alpha and myeloperoxidase levels, apoptotic cells and DNA fragmentation were increased, and testis weight, insulin, FSH, LH, testosterone, glutathione and superoxide dysmutase levels, proliferative cells, ZO-1, occludin, and gap junction protein Cx43 immunoreactivity were decreased in the HFD group. All these hormonal, morphological, oxidative and inflammatory biomarkers were enhanced in the HFD + EXC group. It is thought that exercise protected testicular cytotoxicity by regulating hormonal and oxidant/antioxidant balances and testicular function, inhibiting inflammation and apoptosis, as well as preserving blood-testis barrier.

Hyperbaric oxygen therapy prevents subarachnoid hemorrhage-induced apoptosis and impaired contractility of the rabbit bladder.

AIM: To explore the effects of experimental subarachnoid hemorrhage (SAH) on rabbit urinary bladder and to assess the potential protective effects of hyperbaric oxygen therapy (HBOT). METHODS: A total of 15 male New Zealand white rabbits were divided randomly to one of three groups: group I was spared as the control group (n = 5), group II was exposed to SAH, received no treatment, and acted as the SAH group (n = 5) and group III was exposed to SAH and received five sessions of HBOT (started 12 hours after SAH induction and was given twice daily for the first 2 days and once on the third day) and acted as the treatment group (n = 5). At 72 hours after the SAH induction, bladders from all animals were removed for in vitro organ bath experiments and biochemical analyses. RESULTS: Isometric tension studies revealed that compared to group I, the contractile responses of the strips to carbachol in group II were significantly decreased whereas HBOT restored the contractile responses (P < .05). Caspase-3 and nitric oxide synthase (NOS) activities of bladder tissues were significantly increased in group II when compared with group I, whereas caspase-3 and NOS activities were significantly decreased in the tissues of group III (P < .01). CONCLUSIONS: Subarachnoid hemorrhage stimulates apoptosis of the rabbit bladder and impairs the contractile response of the rabbit bladder to carbachol. HBOT creates a protective effect in rabbit bladder tissues and restores SAH-induced changes.

Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression.

A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg-1  day-1 ) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury.

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 °C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.

Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats.

The aim of this study was to investigate possible protective effects of apocynin (APO), an NADPH oxidase (NOX2) inhibitor, on cisplatin (CIS)-induced testicular damage. Four groups of Sprague Dawley rats were used: control, APO, CIS and CIS+APO. Following a single intraperitoneal dose of CIS (7 mg/kg), either dimethyl sulfoxide or APO (25 mg/kg) was administered orally for 5 days. Testis samples were evaluated microscopically for general histopathology and ultrastructure, proliferating and apoptotic cells, and NOX2 localization. Sperm parameters were evaluated. Malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD), myeloperoxidase (MPO) and 8-hydroxy-2-deoxyguanosine (8-OHdG) activities were analysed biochemically. The CIS group had a greater number of abnormal spermatozoa, atrophic seminiferous tubules, apoptotic and NOX2-immunoreactive cells; numerous large vacuole formations in the cytoplasm of germinal epithelial cells; degenerated intercellular tight junctions; higher MDA, 8-OHdG and MPO levels; decreased numbers of spermatozoa; and lower proliferative index and GSH and SOD levels. All these histologic and biochemical results were better in the CIS+APO group. CIS causes testicular damage by decreasing spermatogenic cell lines and increasing NOX2 activity and apoptosis through oxidative stress. APO prevents testicular damage, possibly by its antioxidant effects.

The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats.

OBJECTIVE: Oxygen free radicals are important components involved in the histopathologic tissue alterations observed during abdominal aortic aneurysms (AAAs). This study examined whether melatonin has protective or therapeutic effects against AAAs. METHODS: Sprague-Dawley rats were divided into four groups. A CaCl2 model was used to induce AAA. Starting on the operation day (Mel+AAA+Mel group) or 4 weeks after the operation (AAA+Mel group), the rats received intraperitoneal melatonin (10 mg/kg/day) for 6 and 2 weeks, respectively. The control and AAA groups received vehicle for 2 weeks after the sham operation and AAA induction, respectively. Angiographic measurements were recorded at the beginning, week 4, and week 6 of the study. After decapitation, aorta tissues were taken for the measurement of malondialdehyde, 8-hydroxy-2'-deoxyguanosine, glutathione levels, and myeloperoxidase and caspase-3 activity. Matrix metalloproteinase (MMP)-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were analyzed by Western blot technique. Aortic tissues were also examined by light microscopy. RESULTS: CaCl2 caused an inflammatory response and oxidative damage indicated by rises in malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. Myeloperoxidase and caspase-3 activities were increased, but glutathione levels were reduced. On the one hand, MMP-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated AAA group. On the other hand, melatonin treatment reversed all of these biochemical indices and histopathologic alterations. CONCLUSIONS: According to the data, although melatonin tended to reverse the biochemical parameters given on week 4, the preventive effect is more pronounced when given concomitantly with AAA induction because values were closer to the control levels.

Melatonin improves hyperglycemia induced damages in rat brain.

BACKGROUND: Diabetes mellitus is an endocrine disorder which is characterized by the development of resistance to the cellular activity of insulin or inadequate insulin production. It leads to hyperglycemia, prolonged inflammation, and oxidative stress. Oxidative stress is assumed to play an important role in the development of diabetic complications. Melatonin is the hormone that interacts with insulin in diabetes. Therefore, in this study, the effects of melatonin treatment with or without insulin were examined in diabetic rat brain. METHODS: Rats were divided into five groups as control, diabetes, diabetes + insulin, diabetes + melatonin, and diabetes + melatonin + insulin. Experimental diabetes was induced by streptozotocin (60 mg/kg, i.p.). Twelve weeks after diabetes induction, rats were decapitated. Malondialdehyde, glutathione, sialic acid and nitric oxide levels, superoxide dismutase, catalase, glutathione-S-transferase, myeloperoxidase, and tissue factor activities were determined in brain tissue. RESULTS: Melatonin alone showed its antioxidant effect by increasing brain glutathione level, superoxide dismutase, catalase, and glutathione-S-transferase activities and decreasing malondialdehyde level in experimental diabetes. Although insulin did not have a significant effect on glutathione and glutathione-S-transferase, its effects on lipid peroxidation, superoxide dismutase, and catalase were similar to melatonin; insulin also decreased myolopeoxidase activity and increased tissue factor activity. Combined melatonin and insulin treatment mimicked the effects of insulin. CONCLUSION: Addition of melatonin to the insulin treatment did not change the effects of insulin, but the detailed role of melatonin alone in the treatment of diabetes merits further experimental and clinical investigation.

Protective effect of platelet-rich plasma on urethral injury model of male rats.

AIMS: Urethral stricture (US) formation is caused by fibrosis after excessive collagen formation following an injury or trauma to the urethra. In this study, we aimed to evaluate the effects of platelet-rich plasma (PRP) on a urethral injury (UI) model of male rats. METHODS: A UI model was used by applying a coagulation current to the urethras of male rats. There were four groups with six rats in each: control group, PRP applied to naive urethra, UI group, and UI with PRP application. PRP was applied to the urethra after a coagulation current-induced injury as soon as possible. On the 14th day, all rats were sacrificed and urethral tissues were investigated for collagen type I, collagen type III, platelet-derived growth factor-α, platelet-derived growth factor-ß, and transforming growth factor-ß using quantitative real-time polymerase chain reaction and Western blot analysis. The effect of urethral damage and healing was evaluated for collagen type I-to-collagen type III ratio. RESULTS: The collagen type I-to-collagen type III ratio was significantly higher in UI group (P < 0.05) than in the others, while UI with PRP application group had comparable results with the control group (P > 0.05). CONCLUSIONS: The results of this study show that PRP has a preventive effect on stricture formation in a UI model of rats, as shown by its effect on collagen synthesis. Further studies that eventually show the effects of PRP on human tissues are necessary and promising.

Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats.

Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-ß1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

Functional and structural changes of the urinary bladder following spinal cord injury; treatment with alpha lipoic acid.

BACKGROUND & AIM: Alpha lipoic acid (LA) was shown to exert neuroprotection in trauma-induced spinal cord injury (SCI), which is frequently associated with urinary bladder complaints in patients with SCI. Accordingly, the protective effects of LA on biochemical and histological changes in bladder as well as functional studies were assessed. METHODS: Wistar albino rats were divided as control, SCI, and LA (50 mg/kg/day, ip) treated SCI groups (SCI+LA). The standard weight-drop (100 g/cm force at T10) method was used to induce a moderately severe SCI. One week after the injury, neurological examination was performed and the rats were decapitated. Bladder samples were taken for histological examination, functional (isolated tissue bath) studies, and for the measurement of biochemical parameters (malondialdehyde, MDA; gluthathione, GSH; nerve growth factor, NGF; caspase-3, luminol and lucigenin chemiluminescences). RESULTS: SCI caused a significant (P < 0.001) increase in the detrusor muscle thickness. It increased the contractility responses to carbachol and relaxation responses to papaverine (P < 0.05-0.001). There were also significant alterations in MDA, caspase-3, luminol, and lucigenin chemiluminescences with concomitant decreases in NGF and GSH (P < 0.05). LA treatment reversed histological and functional (contraction and relaxation responses) changes induced by SCI (P < 0.05-0.001), but no significant recovery was observed in the impaired neurological functions. CONCLUSION: These results indicate that LA have a beneficial effect in improving the bladder tonus via its antioxidant and anti-inflammatory actions following SCI.

Effects of Myrtus communis extract treatment in bile duct ligated rats.

BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Estrogen receptor agonists alleviate cardiac and renal oxidative injury in rats with renovascular hypertension.

Although endogenous estrogen is known to offer cardiac and vascular protection, the involvement of estrogen receptors in mediating the protective effect of estrogen on hypertension-induced cardiovascular and renal injury is not fully explained. We aimed to investigate the effects of estrogen receptor (ER) agonists on oxidative injury, cardiovascular and renal functions of rats with renovascular hypertension (RVH). Female Sprague-Dawley rats were randomly divided as control and RVH groups, and RVH groups had either ovariectomy (OVX) or sham-OVX. Sham-OVX-RVH and OVX-RVH groups received either ERß agonist diarylpropiolnitrile (1 mg/kg/day) or ERα agonist propyl pyrazole triol (1 mg/kg/day) for 6 weeks starting at the third week following the surgery. At the end of the 9(th) week, systolic blood pressures were recorded, cardiac functions were determined, and the contraction/relaxation responses of aortic rings were obtained. Serum creatinine levels, tissue malondialdehyde, glutathione, superoxide dismutase, catalase levels, and myeloperoxidase activity in heart and kidney samples were analyzed, and Na(+), K(+)-ATPase activity was measured in kidney samples. In both sham-OVX and OVX rats, both agonists reduced blood pressure and reversed the impaired contractile performance of the heart, while ERß agonist improved renal functions in both the OVX and non-OVX rats. Both agonists reduced neutrophil infiltration, lipid peroxidation, and elevated antioxidant levels in the heart, but a more ERß-mediated protective effect was observed in the kidney. Our data suggest that activation of ERß might play a role in preserving the function of the stenotic kidney and delaying the progression of renal injury, while both receptors mediate similar cardioprotective effects.

Intravesical hyaluronic acid treatment improves bacterial cystitis and reduces cystitis-induced hypercontractility in rats.

OBJECTIVE: To investigate the effect of intravesical hyaluronic acid on Escherichia coli-induced cystitis and cystitis-induced hypercontractility in rats. METHODS: Bacterial cystitis was induced in Wistar female rats by intravesical inoculation of E. coli. Isotonic saline was instilled in the control group (n = 6). The rats were either non-treated, treated with gentamycin (4 mg/kg, 5 days) or treated intravesically with hyaluronic acid (0.5 mL, 0.5%). On the eighth day, the bladder tissues were excised for histological examination, and the measurements of myeloperoxidase, superoxide dismutase and catalase activities. Contraction/relaxation responses to carbachol, isoprotrenol and papaverine were studied. RESULTS: Tissue myeloperoxidase activity was increased, but superoxide dismutase and catalase activities were decreased in bacterial cystitis, while hyaluronic acid treatment reversed these changes. In the hyaluronic acid-treated group, healing of the uroepithelium was observed, while decreased inflammatory cell infiltration was obvious in gentamycin-treated group. E. coli-induced cystitis in all rats resulted in increased contraction responses to carbachol compared with controls (P < 0.01). Treatment with hyaluronic acid, but not gentamycin, significantly (P < 0.05) depressed hypercontractility at maximum carbachol concentrations. In all rats with cystitis, papaverine-induced relaxation was increased, whereas isoproterenol-induced relaxation curves were not different between the studied groups. CONCLUSION: Gentamycin treatment, despite its ameliorative effect on inflammation, had no impact on the contractile dysfunction of the injured bladder. Intravesical hyaluronic acid, in addition to its supportive role in the healing of the epithelium, seems to lower the increased threshold for contraction and to reduce oxidative stress. These findings support a potential role for hyaluronic acid in the treatment of bacterial cystitis.

Chard (Beta vulgaris var. cicla) extract improved hyperglycemia-induced oxidative stress and surfactant-associated protein alterations in rat lungs.

CONTEXT: Chard is used as an antidiabetic agent by the diabetic patients in Turkey. OBJECTIVE: The effect of chard extract [Beta vulgaris L. var. cicla (Chenopodiaceae)] on the antioxidant system and the expression of surfactant-associated proteins (SP) in the lungs of hyperglycemic rats were examined. MATERIALS AND METHODS: Hyperglycemia was induced by a single dose of streptozotocin (60 mg/kg) provided intraperitoneally. Fourteen days after the rats were rendered hyperglycemic, the chard (2 g/kg/d), insulin (6 U/kg/d), and chard plus insulin (as mentioned above) were administered to rats for 45 d. On day 60, rats' lungs were removed. Oxidative stress parameters and SP expression were assayed. RESULTS: The lungs of hyperglycemic rats were characterized by the induced lipid and protein oxidation, elevated myeloperoxidase and xanthine oxidase activities, decreased glutathione levels, and reduced tissue factor and antioxidant enzymes activities (catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase). Chard treatment alone and chard treatment combined with insulin were capable of achieving a regression of pulmonary oxidative stress, by inhibiting lipid and protein oxidation, and restoring the antioxidant system of hyperglycemic rats. SP-A expressions were significantly unchanged in all groups, whereas pro-SP-C and SP-D expressions were reduced in hyperglycemic rats. Pro-SP-C and SP-D levels were increased by chard and insulin administrations alone and combined in hyperglycemic rats. DISCUSSION AND CONCLUSION: All treatments have a positive effect on the surfactant and antioxidant systems of the lungs of hyperglycemic rats. The best therapeutic effect was provided by treatment with chard extract alone in the compensation of hyperglycemic symptoms.

PHARMACODYNAMICAL EVALUATION OF MATRIX TYPE TRANSDERMAL THERAPEUTIC SYSTEMS CONTAINING CAPTOPRIL.

The objective of this study was to evaluate pharmacodynamical properties of transdermal therapeutic systems (TTS) containing captopril together with synthetic and pH independent polymers, Eudragit RL 100 and RS 100. Optimum formulation was chosen according to the results of our previous study regarding in vitro dissolution and ex vivo diffusion rate studies through excised human skin by using Franz Diffusion Cell. Control group, hypertension group (HT) and TTS containing captopril hypertension group (HT-CAP) were assessed for the pharmacodynamic activity of the study. Pharmacodynamic activity of transdermal patches containing captopril was evaluated in rats by the measurement of systolic blood pressure for 24 h with the use of the tail cuff method. Blood pressure, heart rate, body and heart weight, heart and body weight ratio were determined. Lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO) and Na+, K(+)-ATPase were measured in the serum of rats. Histopathological evaluation of the heart tissue was conducted in order to determine any tissue damage. Blood pressure values of the TTS containing captopril hypertension group were decreased significantly and became almost similar with the blood pressure values of the control group. These results indicated that matrix type transdermal patches prepared with Eudragit RL 100 and RS 100 polymers containing captopril can be considered as transdermal therapeutic systems for chronical treatment of hypertension and congestive heart failure. However, further in vivo pharmacokinetic studies should be performed in order to determine the blood level of the drug.