Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study.

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.

Is Serum Progranulin Level a Biomarker in Autism and Cognitive Development Disorders?

OBJECTIVE: Cognitive developmental delay is a picture of the group of early-onset chronic diseases that affect 1.5-10% of children. Autism spectrum disorders are neurodevelopmental diseases with a genetic basis and abnormal brain development, characterized by disorders in areas that make up interpersonal relationships, such as communication, social cognition, and processing of emotional signals. Immune system dysfunction is thought to play a role in the pathogenesis of some neurological disorders, including autism. Progranulin is thought to be a regulator of the innate immune response. The purpose of this study was to look at plasma levels of progranulin, an anti-inflammatory neurotrophic factor, in children with autism spectrum disorder and cognitive developmental delay. MATERIALS AND METHODS: The study was conducted on 52 children who were patients and 35 healthy children. Of the 52 children of the patient group, 32 were diagnosed with CDD and 20 were diagnosed with cognitive developmental delay-autism spectrum disorder. Serum progranulin concentrations were measured using a human-specific sandwich enzyme-linked immunosorbent assay. RESULTS: Serum progranulin concentration was statistically lower in the patient group (110.746 ± 26.04) than in the healthy control group (137.346 ± 30.02). There was a statistically significant difference between the groups in levels of serum progranulin (P=.000). Receiver operating characteristic analysis was performed to evaluate the potential of progranulin as a biomarker to distinguish patients with cognitive developmental delay-autism spectrum disorder from healthy children. It detected a moderate area under the curve (0.743 ± 0.06) value and a more significant P value for progranulin (P=.000). CONCLUSION: Progranulin deficiency in patients with autism spectrum disorder-cognitive developmental delay may result in decreased neurotrophic support for many years, with cumulative damage associated with unregulated inflammation that may play a role in autism spectrum disorder-cognitive developmental delay. We believe that low progranulin levels could be a biomarker for autism spectrum disorder-cognitive developmental delay.

Treatment of oxidative stress, apoptosis, and DNA injury with N-acetylcysteine at simulative pesticide toxicity in fish.

Pesticide toxicities are common in aquatic ecosystems and affects aquatic livings negative. Therefore, it is important to strengthen the antioxidant system in aquatic organisms and to protect the organisms against these toxic chemicals. In this study, the simulative toxicity was established to the fish then the healing process was followed. For this purpose, rainbow trout Oncorhynchus mykiss exposed to cypermethrin and left to the recovery process with either N-acetyl cysteine (an antioxidant, 0.5 mM-1.0 mM concentrations) or no intervention (self-healing) for 96 h. In this context, paraoxonase (PON), arylesterase (AR), myeloperoxidase (MPO), antioxidant enzymes (SOD, CAT, GPx), acetylcholinesterase (AChE) activities as well as MDA, caspase-3 and 8-OHdG levels were measured in fish gills, liver and kidney tissues. In addition, trace element tests were performed in the tissues sampled for each group. At the result of pesticide exposure, SOD, CAT, GPx, PON, AR and AChE activities were increased but MDA, MPO, caspase-3 and 8-OHdG levels were decreased in N-acetyl cysteine (NAC) treated groups in all tissues compared to self-healing group (p < 0.05). When the element analysis of the samples was examined, tissue-based differences were observed significantly in all application groups (p < 0.05). Considering the results of the study, it was found that NAC administration at high concentration (1.0 Mm NAC) was more effective on pesticide toxicity. It was concluded that the most sensitive tissue was the kidney.

Radiobiological comparison of flattening filter (FF) and flattening filter-free (FFF) beam in rat laryngeal tissue.

PURPOSE: The purpose of this study is to investigate the radioprotective effect of melatonin by analyzing histopathological changes and serum biochemical levels on experimental rat models exposed to flattening filter (FF) and flattening filter-free (FFF) beam. MATERIALS AND METHODS: Forty-eight healthy adult Sprague Dawley rats were randomly divided into six groups. The control (Group 1) was given no treatment, the melatonin (Group 2) was given 10 mg/kg melatonin only, the FF (Group 3) and FFF (Group 5) were given fractionated dose (Total 32 Gy, 5 consecutive days) radiotherapy only, and the FF plus melatonin (Group 4) and FFF plus melatonin (Group 6) were given 10 mg/kg melatonin 15 minutes prior to irradiation. Rats were examined for histopathology and biochemical analysis 10 days after irradiation. RESULTS: When results of FF and FFF radiotherapy only groups are compared to control group, statistically significant difference in histopathological and biochemical parameters are observed; however, melatonin administration in radiotherapy plus melatonin groups improved these parameters (p <.05). In addition, there was no statistically significant difference between FF and FFF beams (p > .05). CONCLUSIONS: The effect of low- and high-dose beams on the rat larynx and serum samples were investigated histopathologically and biochemically for the first time. We observed that melatonin supplemented before FF and FFF radiotherapy protected early period radiotherapy-induced laryngeal mucosal damage. Since the radiobiological results of FF and FFF beams are similar, FFF beams can be safely applied in laryngeal irradiation. However, more experimental rat and clinical studies are needed to clarify the radiobiological uncertainy concerning dose rate on cancerous and healthy tissue.

Radioprotective effect of melatonin against radiotherapy-induced cerebral cortex and cerebellum damage in rat.

PURPOSE: The present study aims to investigate the radioprotective effect of melatonin (MEL) against early period brain damage caused by different dose rate beams in the experimental rat model. MATERIALS AND METHODS: Forty-eight Sprague Dawley rats were randomly divided into six groups; the control, only melatonin, low dose rate-radiotherapy (LDR-RT), high dose rate-radiotherapy (HDR-RT) groups and (LDR-RT) + MEL and (HDR-RT) + MEL radiotherapy plus melatonin groups. Each rat administered melatonin was given a dose of 10 mg/kg through intraperitoneal injection, 15 minutes before radiation exposure. The head and neck region of each rat in only radiotherapy and radiotherapy plus melatonin groups was irradiated with a single dose of 16 Gy in LDR-RT and HDR-RT beams. Rats in all groups were examined for histopathology and biochemistry analysis 10 days after radiotherapy. RESULTS: Comparing the findings for LDR-RT and HDR-RT only radiotherapy groups and the control group, there was a statistically significant difference in histopathological and biochemical parameters, however, melatonin administered in radiotherapy plus melatonin groups contributed improving these parameters (p < .05). There was no statistically significant difference between LDR-RT and HDR-RT beams (p > .05). CONCLUSIONS: It was concluded that melatonin applied before LDR-RT and HDR-RT radiotherapy protected early period radiotherapy-induced brain damage. The effects of clinically low and high dose beams on the cerebral cortex and cerebellum were investigated histopathologically for the first time. HDR beams can be safely applied in brain radiotherapy. However, more experimental rat and clinical studies are needed to explain the radiobiological uncertainties about the clinic dose rate on different cancerous and healthy tissues.

The effect of N-acetylcysteine supplementation on the oxidative stress levels, apoptosis, DNA damage, and hematopoietic effect in pesticide-exposed fish blood.

Cysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N-acetylcysteine (NAC) were applied for a 4-day treatment period and compared with the group of the self-healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein-cholesterol [LDL-C], sodium, and potassium), were found to be importantly different among all groups at the P < 0.05 level, while 8-hydroxydeoxyguanosine and caspase-3 levels were determined to be high in the pesticide group but decreased significantly in NAC-treated groups ( P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0 mM NAC. NAC has an important therapeutic effect on pesticide-induced hematoxicity for fish in terms of all the data.

Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa.

Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation. Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats. Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later. Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage. Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.

Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS.

The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1ß, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system.

The protective effects of IgM-enriched immunoglobulin and erythropoietin on the lung and small intestine tissues of rats with induced sepsis: biochemical and histopathological evaluation.

CONTEXT: Sepsis continues to be a significant problem for critical care patients. OBJECTIVE: To evaluate the protective effects of IgM-enriched immunoglobulin and erythropoietin on pulmonary and small intestine tissues in a rat model of intra-abdominal sepsis induced via the cecal ligation and puncture (CLP) method. MATERIALS AND METHODS: Male Sprague-Dawley rats were used. Control group (n = 6): surgical procedure was not performed. Laparotomy was only performed in the sham group (n = 6) and CLP was only performed in the sepsis (CLP) group (n = 30). After erythropoietin (2000 U/kg, intraperitoneal) was given in the sepsis + erythropoietin (CLP + EPO) group (n = 30), IgM-enriched immunoglobulin (600 mg/kg, intraperitoneal) was given in the sepsis + pentaglobin (CLP + PEN) group (n = 30), CLP was created. Intracardiac blood samples were collected for biochemical analysis; lung and small intestine tissue samples were removed for histopathological evaluation. RESULTS: Plasma TNF-α levels (pg/ml) were similar among CLP, CLP + EPO, and CLP + PEN groups (204.0 ± 52.4, 198.5 ± 17.3, and 214.6 ± 93.6, respectively). The CLP group had higher plasma IL-1ß levels (pg/ml) compared with CLP + EPO and CLP + PEN groups (325.1 ± 134.1, 164.3 ± 25.6, and 186.3 ± 26.0, respectively) (p < 0.05). Rats in CLP + EPO and CLP + PEN groups had abolished histopathologic appearance of lung and small intestine tissues compared with rats in the CLP group. DISCUSSION AND CONCLUSION: Our findings support the use of EPO and IgM-enriched immunoglobulin in the prevention of lung and small intestine injuries associated with sepsis.

Potential anticancer activity of carvone in N2a neuroblastoma cell line.

Carvone (CVN) is a monocyclic monoterpene found in the essential oils of Mentha spicata var. crispa (Lamiaceae) and Carum carvi L. (Apiaceae) plants and has been reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor activities. The beneficial health properties of CVN have encouraged us to look into its anticancer activity. To the best of our knowledge, reports are not available on the anticancer activity of CVN in cultured primary rat neuron and N2a neuroblastoma (NB) cells. Therefore, the present study is an attempt toward exploring the potential anticancer activity of CVN, if any, in cultured primary rat neuron and N2a NB cells. Our results indicated that CVN (only at 25 mg/L) treatment led to an increase in the total antioxidant capacity levels in cultured primary rat neuron cells compared with control cells. Also, CVN (at concentrations higher than 100 mg/L) treatment led to an increase in the total oxidative stress levels in both cell types. The mean values of the total scores of cells showing DNA damage (for comet assay) were not found to be significantly different from the control values in both cells (p > 0.05). On the other hand, after 24 h treatment with CVN, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay showed that CVN application significantly reduced the cell viability rates in both cell types at concentrations higher than 100 mg/L. Summarizing, our data suggest that CVN represents little potential for promising anticancer agent to improve brain tumors therapy.

Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration.

AIM: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA), and nitric oxide (NO), as well as activity of endothelial NO synthase (eNOS), in patients with age-related macular degeneration (AMD). METHODS: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30) were compared to a control group with no retinal pathology (n=30). RESULTS: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001), whereas NO levels and eNOS activity were higher in the control group (P<0.001). In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively. CONCLUSION: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy.

AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS: Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION: The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.

The biochemical and histopathological investigation of amlodipine in ethylene glycol-induced urolithiasis rat model.

BACKGROUND: Urinary calculi are a common and severe problem, which are formed by urolithiasis or by the formation of calcium oxalate (CaOx) crystals in the kidneys. Many treatment options such as drugs, various herbal preparations, surgical removal of the stones, and extracorporeal shock wave lithotripsy have been applied for this condition. The aim of this study is to assess the effects of the drug amlodipine in an experimentally induced urolithiasis rat model. MATERIALS AND METHODS: The effect of 5 mg/kg amlodipine was studied in rats that were first treated with 1% ethylene glycol and 1% ammonium chloride for 21 days to induce urolithiasis. The weight differences and the levels of calcium, magnesium, and phosphate were measured in serum and urine. In addition, urine CaOx level was defined and histopathological analyses were performed on the kidneys. RESULTS: Urolithiasis caused a significant increase in both serum and urine parameters compared with healthy rats. Urolithiasis plus amlodipine administration increased the levels of these same parameters. Urine CaOx level was high in urolithiasis rats and was also increased by urolithiasis plus amlodipine administration. The weight of the rats decreased in the urolithiasis plus amlodipine group when compared with the urolithiasis group. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in the urolithiasis group and the amlodipine treatment group. CONCLUSION: We showed that amlodipine may increase susceptibility to urolithiasis by raising hyperoxaluria and hypercalciuria. Further studies should be performed to elucidate the urolithiasis activity of amlodipine and to confirm the data.

Nigella sativa reduces tissue damage in rat ovaries subjected to torsion and detorsion: oxidative stress, proinflammatory response and histopathological evaluation.

BACKGROUND: To evaluate biochemically and histopathologically the effects of Nigella sativa (NS) in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. METHODS: Thirty-six female rats were divided into 6 groups: group I = sham operation; group II = 500 mg/kg NS + sham operation; group III = bilateral ovarian ischemia; group IV = 500 mg/kg NS + ischemia; group V = 3-hour period of ischemia + 3-hour reperfusion, and group VI: 3-hour period of ischemia + 500 mg/kg NS 2.5 h after the induction of ischemia + 3-hour reperfusion. At the end of ischemia, the bilateral vascular clips were removed, and 3-hour reperfusion was continued. IL-1ß, IL-6, and TNF-α cytokine levels in serum, and superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH), and malondialdehyde (MDA) levels were determined. RESULTS: I/R increased the MDA level and MPO activity while significantly decreasing the SOD activity and GSH level when compared to the sham. The 500-mg/kg dose of NS before I/R reversed the trend in MDA levels, MPO activity, SOD activity, and GSH levels. Ischemia and I/R increased the serum levels of IL-1ß, IL-6, and TNF-α, while the administration of NS decreased the serum levels of these cytokines. CONCLUSIONS: The administration of NS is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.

Comparing effects of lacidipine, ramipril, and valsartan against experimentally induced myocardial infarcted rats.

In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents.

Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. MATERIALS AND METHODS: The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. RESULTS: The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. CONCLUSION: More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment.

Preventive effect of amiodarone during acute period in isoproterenol-induced myocardial injury in Wistar rats.

The ability of amiodarone to prevent pathological changes and oxidative stress after isoproterenol (ISO)-induced myocardial injury was investigated in rats. A better understanding of the processes involved in the pathophysiology of myocardial infarction has led to the search for drugs that can limit the extent of myocardial injury. Amiodarone was administered to groups of rats once per day for 30 days. On days 29 and 30, the rats of the ISO control and drug treatment groups were administered 180 mg/kg ISO subcutaneously at an interval of 24 h for two consecutive days. In the control groups, clinical indicators, such as creatine kinase-isoenzymes and troponin-I, were found to be statistically higher than in the drug groups. Parallel to this increase in indicators, a significant decrease in glutathione levels and activities of superoxide dismutase and an increase in malondialdehyde level were detected. Biochemical and histopathologic results in the ISO-induced model of myocardial injury emphasize the beneficial action of amiodarone as a cardioprotective agent.

Investigation of effects of Lacidipine, Ramipril and Valsartan on DNA damage and oxidative stress occurred in acute and chronic periods following isoproterenol-induced myocardial infarct in rats.

In this study, effects of Lacidipine (LAC), Ramipril (RAM) and Valsartan (VAL) on DNA damage and oxidative stress occurred in acute and chronic periods after isoproterenol (ISO)-induced myocardial infarct (MI) were investigated in rats. LAC, RAM and VAL had been administered by oral gavage at 3, 3 and 30 mg/kg doses, respectively, in acute and chronic periods following MI. In acute MI model, LAC, RAM and VAL had been administered once per day to rat groups during 30 days. On days 29 and 30, the rats of the acute MI control and drug treatment groups were administered 180 mg/kg ISO, subcutaneously at an interval of 24 h. In chronic MI model, LAC, RAM and VAL had been administered to rat groups during 30 days, and on the 1st and 2nd days, the rats of the chronic MI control and drug treatment groups were administered ISO, by the same way. After this period, routine biochemistry indicators of MI, alanin aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-isoenzymes (CK-MB), troponin I (TnI) and nitric oxide (NO), oxidative stress indicator, has been measured in the serums obtained from rat's blood. Also, 7,8-Dihydro-8-oxo-guanine (8-OHGua), which is an indicator of DNA damage level, has been determined in whole blood. After MI diagnosis, the relationships among the 8-OHGua, NO and clinic MI indicators have been determined. Results have been evaluated by comparing with that of control group. In control groups, the clinic MI indicators have been found to be statistically higher than the drug groups. In parallel to this increase in MI indicators, there have been determined a significant decrease in NO levels and an increase in 8-OHGua level. There was no significant difference in the rat groups which received drugs without MI induction. We have observed that the level of 8-OHGua which increased after MI in both acute and chronic periods decreased by LAC, RAM and VAL when compared to acute and chronic MI control groups. In conclusion, it has been determined that oxidative stress has been increased after ISO induced MI model and this stress reduces NO and even damages DNA. LAC, RAM and VAL may decrease the severity of MI and prevent DNA damage by reducing oxidative stress.

Effects of Lacidipine, Ramipril and Valsartan on Serum BNP Levels in Acute and Chronic Periods Following Isoproterenol-Induced Myocardial Infarction in Rats.

OBJECTIVE: Myocardial infarction (MI) as a result of cardiovascular disease is the principal cause of death in both developed and developing countries. Brain natriuretic peptide (BNP) is an important marker of cardiac failure. Cardioprotective activities of the antihypertensive drugs lacidipine (LAC), ramipril (RAM) and valsartan (VAL), against isoproterenol (ISO)-induced MI, have been determined. However, the levels of BNP, an indicator of left ventricular failure, have not been evaluated. MATERIALS AND METHODS: This study investigated the effects of LAC, RAM and VAL on serum BNP levels in acute and chronic periods after ISO-induced MI in rats. RESULTS: Serum BNP was found to be significantly increased in the acute MI model, but not in the chronic MI model. RAM and VAL application decreased BNP levels that had been increased after acute MI induction. Additionally, no significant differences were seen in chronic MI+drug groups compared with both intact and chronically infarcted control groups. CONCLUSION: The acute MI model, but not the chronic MI model, was associated with increased serum BNP levels. Pre-treatment with RAM and VAL, but not LAC, prevented the acute MI-induced increase in serum BNP levels, suggesting that inhibition of the renin-angiotensin system has prophylactic effects in the acute MI model. Therefore, both RAM and VAL may become first-line drugs for the treatment of hyper-tensive patients who are at high risk for cardiovascular failure.

Protective effects of N-acetylcysteine and Ginkgo biloba extract on ischaemia-reperfusion-induced hepatic DNA damage in rats.

Hepatic ischaemia-reperfusion injury is a serious problem that occurs during various surgical operations such as liver transplantation, surgical revascularization, and partial organ resection. Different pharmacological agents have been used for the protection of organ function and for extending the tolerable ischaemic interval after the ischaemic insult. We aimed to determine the presence of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA from liver undergoing ischaemia-reperfusion, and also to evaluate the protective effects of N-acetylcysteine (NAC) and EGb761 (Ginkgo biloba extract) against hepatic oxidative DNA damage. A total of 40 rats were divided into four groups of 10 animals each (sham-operation group, control group, NAC group, and EGb761 group). Oxidative damage to DNA was evaluated by measuring the increase in 8-OHdG formation in liver tissue and also the effects of NAC and EGb761 pretreatment. Hepatic ischaemia for 90 min followed by reperfusion caused a marked increase in tissue levels of 8-OHdG, thiobarbituric acid-reactive substance, serum ALT, AST and LDH activities compared to sham-operated group. Pretreatment with both NAC and EGb761 clearly diminished 8-OHdG formation and lipid peroxidation. These findings suggest that antioxidant molecules such as NAC and EGb761 may be useful in preventing postischaemic reperfusion injury in hepatic tissue.