Changes in heavy metal levels, reproductive characteristics, oxidative stress markers and testicular apoptosis in rams raised around thermal power plant.

Male reproductive dysfunction is one of the damages in the organism caused by heavy metals. In this study, it was aimed to investigate the changes in heavy metal levels in serum and testicular tissue, and serum hormone levels, epididymal spermatozoa characteristics, tissue oxidative stress levels, testicular histology and testicular apoptosis level in rams raised in remote and near regions of a thermal power plant. A total of 75 rams were divided into 3 groups according to the regions, where they were born and raised, being far [250 km distance, group 1 (control), n = 25], close (20 km distance, group 2, n = 25) and very close (10 km distance, group 3, n = 25) to the thermal power plant. The blood along with testis and epididymis tissues was taken from the animals after slaughtering. In addition, soil and water heavy metal analyzes were also performed. The highest levels of serum Al, Cr, As, Ag, Sn and testicular Al, V, Ni, Ag, Cd, Cr, As, Pb, and the lowest levels of serum Cu, testicular Cu and Zn were determined in group 3 compared to control. Soil and water heavy metal results were similar to those found in serum and testis. The lowest serum testosterone level, tissue glutathione-peroxidase and catalase activities, spermatozoon concentration, and the highest tissue malondialdehyde level, dead spermatozoon rate, Bax apoptotic protein expression level and Bax/Bcl-2 rate alongside some testicular histopathological lesions were found in group 3 in comparison to control. Significant correlations were determined between some heavy metal levels and some parameters measured. As a result, heavy metals accumulate in the soil and water in the region close to the thermal power plant. The endocrine and exocrine reproductive potentials of rams born and grown in these regions were clearly damaged by the increased testicular heavy metals due to water drank and herbs consumed.

Preventive effect of Rumex crispus L. on surgically induced intra-abdominal adhesion model in rats.

BACKGROUND: Rumex crispus L. (Polygonaceae), known as "Labada" in Turkey, was reported to be used for the treatment of gynecological diseases such as postpartum complications and infertility in folk medicine. Earlier studies on R. crispus have shown that leaf, fruit and root extracts have anti-inflammatory and antioxidant activities and are used for the treatment of tumors in the uterus. The hypothesis of this study is that R. crispus may generate potential anti-adhesive activity against complex factors such as inflammation, oxidation and fibrosis. OBJECTIVES: We aimed to investigate the potential anti-adhesive activity of aqueous methanol extracts of leaves, fruits and roots of R. crispus. METHODS: Abdominal adhesion model was performed in 72 female Wistar Albino rats. In the first step of the experiment, the rats were divided into six groups namely, Sham, Control, Reference and Experimental Groups (consisting of three sub-groups in which R. crispus leaf, fruit and root extracts were applied at 100 mg/kg dose). The test samples were administered once to the peritoneal cavity and the rats were sacrificied at the end of the 14th day. Root extract showed prominent activity, therefore this extract was subjected to fractionation to obtain 3 fractions (30-60-100% methanol fractions) by using vacuum-liquid chromatography. In the second stage, animals were divided into 6 groups as Sham, Control, Reference and Experimental Groups (R30, R60, R100 at 100 mg/kg dose). Adhesion scoring, tissue total antioxidant and oxidant levels, histopathological and immunohistochemical (TNF-α, IL-6 and IL-8) analyzes were performed. RESULTS AND CONCLUSION: Adhesion scores, inflammatory cytokines and inflammation cells decreased by the application of R. crispus root extract. The fractions also showed similar anti-inflammatory effects, but R60 was found to be more effective in prevention of intra-abdominal adhesions and uterine fibrosis. R60 fraction, possessing potential bioactivity, was investigated in terms of phenolic composition by HPLC.

Healing effects of Cornus mas L. in experimentally induced ulcerative colitis in rats: From ethnobotany to pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical studies conducted in Turkey and other countries have revealed that Cornus mas L., from the family Cornaceae have been used against stomachache, diarrhea and colitis. AIM OF THE STUDY: The objective the present study is to determine the possible activity of C. mas in experimentally induced ulcerative colitis in rats and to identify its phytochemical feature. MATERIALS AND METHODS: 2,4,6-Trinitrobenzene sulfonic acid-induced colitis model was induced in rats. The rats were orally treated with different doses (50, 100, 200 and 400 mg/kg) of C. mas 80% methanol extract for 14 days. Increase in body weight, consumed amount of feed, form of the stool, presence of rectal prolapse were followed every day. At the end of the experiment, colon tissues were removed and wet weights for each animal were measured and colon damages were scored. Total antioxidant and total oxidant status, cytokine (TNF-α and IL-1ß) and protein levels of colon tissues were evaluated and histopathological analyses were carried out. After the detection of the effective dose as 400 mg/kg, the aqueous methanol extract was fractionated by using liquid-liquid fractionation technique and the sub-extracts were also tested for in vivo biological activities. High Performance Liquid Chromatography analyses were conducted to determine the phytochemical profile of the active crude extract and n-butanol sub-extract. RESULTS: Amount of feed consumed per day and increase in body weight were the lowest in the control group, while those values were determined to be the highest in 80% methanol extract (at 400 mg/kg dose), n-butanol sub-extract and reference groups. Following colitis induction, it was determined that the fecal form was yellow-slippery in all groups and returned to normal after the treatment with C. mas extracts. Rectal prolapse score was less in the extract (400 mg/kg) and n-butanol sub-extract treated groups. Total antioxidant, total oxidant status, cytokine and protein levels were found to be in parallel with macroscopic findings. 80% methanol extract (400 mg/kg) and n-butanol sub-extract provided the best healing according to the wet weight measurements and colon damage scoring performed on the removed colon tissues. These findings supported the results of histopathological analysis. According to the chromatographic analysis, ellagic acid was determined in both extracts and its amount was quantified. CONCLUSIONS: The present study has verified the ethnomedical use of C. mas for the treatment of ulcerative colitis.

Evaluation of ameliorating effect of lycopene against testicular toxicity due to diethylnitrosamine using biochemical, spermatological and histopathological data.

The aim of this study was to evaluate the possible therapeutic or protective effects of lycopene on diethylnitrosamine (DEN)-induced testicular lipid peroxidation and on the associated changes in spermatological parameters and histopathological architecture of rat testis. DEN is a carcinogenic substance that can be derived from chemicals used in agriculture, such as insecticides and nitrate. The rats were assigned to control, lycopene, DEN(1), DEN(2), lycopene + DEN(1), lycopene + DEN(2), DEN(1) + lycopene and DEN(2) + lycopene groups. During the study, lycopene was administered by oral gavage at a dose of 10 mg kg-1  bw-1 every other day for 10 days and DEN was administered at a dose of 200 mg  kg-1  bw-1 as a single dose intraperitoneally. DEN was applied for 30 days in group DEN(1) and for 90 days in group DEN(2). Malondialdehyde (MDA) and reduced glutathione (GSH) levels, antioxidant enzymes activities, spermatological parameters, the weight of the reproductive organs (v. seminalis, prostate, testis and epididymis) and the histopathological structure were determined. MDA levels significantly increased, while GSH and antioxidant enzymes' activities decreased in DEN groups (p < 0.001). There was an increase in the rate of abnormal spermatozoa and a decrease in sperm density and motility, and reproductive organ weight (the weight of the right and left testis) in both DEN groups. Lycopene has normalised biochemical and spermatological parameters and reproductive organ weight. The histopathological examination of testicular tissue showed that the most significant histopathological change in DEN groups was the seminiferous tubule dilatation. These results suggest that besides the protective effects, the therapeutic effect of lycopene is possibly due to its antioxidant effects on DEN-induced testicular toxicity.

Activity evaluation on Ribes species, traditionally used to speed up healing of wounds: With special focus on Ribes nigrum.

ETHNOPHARMACOLOGICAL RELEVANCE: Ribes species are usually evergreen shrubs, represented by eight species in Turkey. Although they are known for their fruits with commercial importance, their leaves have been used as folk remedy in various areas in Turkey by rural population owing to their wound healing potential. AIM OF THE STUDY: In the present study we aimed to assess the wound healing activity of the leaves of Ribes species growing in Turkey, namely, Ribes alpinum L., R. anatolica Behçet, R. petraeum Wulfen, R. multiflorum Kit. ex Romer & Schultes, R. nigrum L., R. orientale Desf., R. rubrum L., R. uva-crispa L. MATERIALS AND METHODS: Wounds were surgically induced on the dorsal parts of the rats and mice. Prepared herbal ointments were topically applied onto the wounds once daily. The effects of the extracts were evaluated by measuring the breaking strength and percentage of reduction in wounded area by comparing the results with the registered reference ointment, FITO Krem®. Histopathological and antioxidant assays were also conducted. Since, R. nigrum was determined to be the most active species, we further investigated the wound healing potential of the subextracts of the methanol extract of R. nigrum leaves. RESULTS: R. nigrum and R. multiflorum extracts significantly increased wound breaking strength. Significant reduction in the areas was determined for the wounded tissues treated with the ointments of R. nigrum and R. multiflorum extracts. Oxidative Stress Index was found to be lowest for R. orientale, R. nigrum and R. multiflorum. Among the subextracts of R. nigrum, ethyl acetate subextract was found to have promising effect. CONCLUSIONS: Methanol extracts of leaves of R. nigrum and R. multiflorum demonstrated significant wound healing effect. We can suggest that ethyl acetate subextract of R. nigrum may be a potential candidate to be used for the development of a wound healing agent.

In vitro and histological investigation of antitumor effect of some triazole compounds in colon cancer cell line.

1,2,4-Triazoles are used as antifungal, antibacterial, antimicrobial, and antioxidant against some oxidative radical species. Recently, many 1,2,4-triazoles continue to be synthesized. In this study, the effect of the 1,2,4-triazole derivatives on human colon cancer (HT29) was investigated in vitro and in vivo in rats. MTT test was applied to in in vitro experiments. For in vivo study, rats were divided into seven groups as follows: Control group (negative control), azoxymethane (AOM), AOM + cisplatin 15, AOM + L1, AOM + L2, AOM + L3, and AOM + L4. To create colon cancer, the AOM injection was injected subcutaneously at a dose of 15 mg/kg, three times (once weekly). The in vivo studies were completed at 28 weeks. It was found that the 1,2,4-triazole derivatives reduced the cell viability (P < 0.05). In all animals in the experimental groups, mild dysplasia was detected in 100% of the colon mucosal epithelium. Severe dysplasia and adenocarcinoma were observed in L1 groups. As a result, this study determined that the 1,2,4-triazole derivatives exhibit antitumor activity.

In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles.

The 1,2,4-triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti-inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1-M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC50 values lower than 10 µM concentrations. The low IC 50 values of the compounds are M1 (3.88 µM), M2 (2.18 µM), M3 (4.2 µM), M4 (2.58 µM), M5 (2.88 µM), M6 (2.37 µM), M7 (3.49 µM), M8 (4.01 µM), M9 (8.90 µM), and M10 (3.12 µM).

Clinical, pathological and molecular evaluations and CT scan screening of coenurosis (Coenurus cerebralis) in sheep and calves / Avaliação clínica, patológica e molecular e tomografia computadorizada de cenurose (Coenurus cerebralis) em carneiros e bezerros

Abstract The aims of this study were to diagnose coenurosis by means of computerized tomography (CT) scan imaging and molecular characterization of the CO1 gene using the polymerase chain reaction (PCR). Sheep and calves were necropsied, and CT scans on the cephalic region were performed on the animals. Sections of brain tissue infected with parasites were then stained with hematoxylin and eosin for microscopic examination. Material collected from brain cysts was fixed in 70% ethanol. PCR amplification was carried out using the CO1 mitochondrial gene. A total of 60 calves and 80 sheep were examined clinically and, of these, 15 calves and 38 sheep showed signs of depression, with counterclockwise circling movements and altered head carriage. Four sheep and one calf were necropsied, and C. cerebralis cysts were detected in all of them. A hypodense cyst was monitored in the right cerebellar hemisphere on a CT scan on one sheep. A cyst was found in the left frontal lobe on a CT scan on one calf. Microscopically, C. cerebralis cysts were surrounded by a fibrous or epithelial wall that presented necrosis on cerebral sections of both the sheep and the cattle. The CO1-PCR assay yielded a 446 bp band, which was sequenced and phylogenetically analyzed: the results confirmed the presence of T. multiceps. This study reports the first use of CT imaging on naturally infected calves and sheep for diagnosing coenurosis.

Resumo Os objetivos deste estudo foram diagnosticar cenurose por tomografia computadorizada (CT) por imagem de digitalização e caracterização molecular do gene CO1, usando a Reação em Cadeia da Polimerase (PCR). Ovelhas e bezerros foram necropsiados, e uma tomografia computadorizada da região cefálica foi realizada nos animais. Em seguida, cortes microscópicos de cérebro infectado com parasitas foram corados com hematoxilina e eosina e posterior avaliação ao microscópio de luz. Em seguida, o material recolhido de cada cisto cerebral foi fixado em etanol a 70%. A amplificação pela PCR foi realizada utilizando-se o gene mitocondrial CO1. Um total de 60 bezerros e 80 ovelhas foram clinicamente examinados e, desses, 15 bezerros e 38 ovelhas apresentaram sinais de depressão, com movimentos circulares em sentido anti-horário, e desvio da cabeça. Quatro carneiros e uma vitela foram necropsiados, e cistos de C. cerebralis foram detectados nos animais. Um cisto hipodenso foi monitorado no hemisfério cerebelar direito por imagem do CT de um carneiro. O cisto foi encontrado no lobo frontal esquerdo por imagem do CT de um bezerro. Microscopicamente, cistos de C. cerebralis foram envolvidos por uma parede fibrosa ou epitelial, apresentando necrose em ambos os cortes cerebrais de ovinos e de bovinos. O ensaio CO1-PCR produziu uma banda de 446 pb, sequenciado e submetido à filogenia, confirmou ser T. multiceps. Este estudo relata a primeira utilização de imagens de CT em bezerros e ovelhas naturalmente infectados para o diagnóstico de coenurosis.

Clinical, pathological and molecular evaluations and CT scan screening of coenurosis (Coenurus cerebralis) in sheep and calves.

The aims of this study were to diagnose coenurosis by means of computerized tomography (CT) scan imaging and molecular characterization of the CO1 gene using the polymerase chain reaction (PCR). Sheep and calves were necropsied, and CT scans on the cephalic region were performed on the animals. Sections of brain tissue infected with parasites were then stained with hematoxylin and eosin for microscopic examination. Material collected from brain cysts was fixed in 70% ethanol. PCR amplification was carried out using the CO1 mitochondrial gene. A total of 60 calves and 80 sheep were examined clinically and, of these, 15 calves and 38 sheep showed signs of depression, with counterclockwise circling movements and altered head carriage. Four sheep and one calf were necropsied, and C. cerebralis cysts were detected in all of them. A hypodense cyst was monitored in the right cerebellar hemisphere on a CT scan on one sheep. A cyst was found in the left frontal lobe on a CT scan on one calf. Microscopically, C. cerebralis cysts were surrounded by a fibrous or epithelial wall that presented necrosis on cerebral sections of both the sheep and the cattle. The CO1-PCR assay yielded a 446 bp band, which was sequenced and phylogenetically analyzed: the results confirmed the presence of T. multiceps. This study reports the first use of CT imaging on naturally infected calves and sheep for diagnosing coenurosis.

Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-ß1 genes in a rat model of lung ischemia/reperfusion.

OBJECTIVES: Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue's life. MATERIALS AND METHODS: It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-ß1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis. RESULTS: We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-ß1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control. CONCLUSION: These findings suggest that I/R injury may trigger apoptotic mechanism in lung.

Palosuran treatment effective as bosentan in the treatment model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p < 0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p = 0.001). Finally, 50-125-µm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p < 0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p < 0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.

Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-ß1 (TGF-ß1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-ß1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50-125-µm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-µm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.

Prolidase could act as a diagnosis and treatment mediator in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with unknown etiology and pathogenesis. With high mortality risks, most of the IPF cases emerged after a damage of alveolar epithelium, where this situation stimulates the over expression of matrix components. Inflammatory process observed as a reaction to emerged damage. Prolidase as an iminodipeptidase significantly increased during the development of fibrosis. The aim of this study is to measure prolidase activity as a marker of treatment and diagnosis in an experimental lung fibrosis animal model. Thirty male Wistar rats randomly divided into three experimental groups, with ten rats in each group. Group 1, control group; group 2, bleomycin (BLM)-induced lung fibrosis group, and group 3, BLM-induced lung fibrosis treated with palosuran (urotensin-II receptor antagonist). For histopathology, the middle lobes of right lungs were embedded in paraffin, followed by fixation in 10 % buffered formalin, and evaluation of IPF was performed using the Ashcroft scoring method. Prolidase activity was determined by a photometric method based on the measurement of proline levels produced by prolidase. The fibrosis scores and the prolidase activity were significantly enhanced by BLM stimulation. The BLM + palosuran treatment decreased prolidase activity in group 3. There was a positive correlation between prolidase activity and fibrosis scores. Palosuran seems to be effective in the treatment of lung fibrosis, and prolidase activity can be used for the diagnosis and/or for management of the treatment. However, further clinical and experimental studies with animals and/or patients are needed to verify these conclusions.

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages.

The aim of the present study was to investigate whether ellagic acid (EA) has protective effect on adriamycin (ADR)-induced testicular and spermatozoal toxicity associated with the oxidative stress in male rats. Thirthy-two healthy 8-week-old male Sprague-Dawley rats were equally divided into four groups. The first (EA) group was treated with EA (2 mg/kg/every other day) by gavage. The second (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and EA was given to the third (ADR+EA) group. The forth (control) group was treated with placebo. At the end of the 8-week treatment period, reproductive organ weights, epididymal sperm parameters, histopathological changes and apoptosis via Bax and Bcl-2 proteins, testicular tissue lipid peroxidation, and antioxidant enzyme activities, were investigated. ADR administration was determined to cause significant decreases in reproductive organ weights, epididymal sperm concentration and motility, plasma testosterone concentration, diameter of seminiferous tubules, germinal cell layer thickness, Johnsen's testicular score and Bcl-2 positive antiapoptotic cell rate, wherease it caused significant increases in level of lipid peroxidation and glutathione, catalase activity, abnormal sperm rates and Bax positive apoptotic cell rates along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue when compared with the control group. EA administration to ADR-treated rats provided significant improvements in ADR-induced disturbed oxidant/antioxidant balance, decreased testosterone concentration, testicular apoptosis and mild improvements in the histopathological view of the testicular tissue. However, EA failed to improve decreased reproductive organ weights and deteriorated sperm parameters due to ADR administration. It is concluded that while ADR has direct or indirect (lipid peroxidation) negative effects on sperm structure and testicular apoptosis in rats, EA has protective effects on ADR-induced testicular lipid peroxidation and apoptosis.

The efficiency of a urotensin II antagonist in an experimental lung fibrosis model.

Pulmonary fibrosis is a chronic disease. Urotensin II (U-II) is a new peptide with angiogenic and profibrotic features. Therefore, we aim to evaluate the antagonism of U-II with palosuran in an animal model and plan to measure U-II, endothelin-1 (ET-1), and transforming growth factor-ß1 (TGF-ß1) and their association with lung fibrosis. Thirty Wistar male rats were used in the study and were divided into three groups: group 1, control; group 2, bleomycin-induced lung fibrosis group; and group 3, bleomycin-induced lung fibrosis with treatment palosuran group. U-II level (nanograms per milliliter) was 2.957 ± 0.159 in group1, 3.188 ± 0.122 in group 2, and 2.970 ± 0.165 in group 3 (p = 0.002). The ET-1 level (picograms per milliliter) was 4.486 ± 0.376 in group 1, 9.086 ± 1.850 in group 2, and 4.486 ± 0.376 in group 3 (p < 0.001). The TGF-ß1 (nanograms per milliliter) level was 73.143 ± 9.96 in group 1, 84.81 ± 4.73 in group 2, and 77.86 ± 5.77 in group 3 (p = 0.006). Finally, the fibrosis score was 0.7 ± 0.48 in group 1, 4.4 ± 1.34 in group 2, and 3.2 ± 0.63 in group 3 (p < 0.001). There is a statistically significant positive relationship between fibrosis scores and the UT-II, ET-1, and TGF-ß1 levels of the experimental lung fibrosis model. We believe U-II is an important mediator in lung fibrosis models, and its antagonism with palosuran could be a new treatment choice for interstitial lung fibrosis, but further studies need to be conducted to verify the findings of the current study.

Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced spermiotoxicity and testicular apoptosis.

This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5 mL/rat slightly alkaline solution+0.5 mL/rat corn oil every other day. The LC group was treated with 0.5 mL/rat slightly alkaline solution+0.5 mL/rat corn oil containing 10 mg/kg of LC every other day. The EA group received 0.5 mL/rat corn oil+0.5 mL/rat slightly alkaline solution containing 2 mg/kg of EA every other day. The TCDD group received 0.5 mL/rat corn oil containing 100 ng/kg/day of TCDD+0.5 mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5 mL/rat TCDD+0.5 mL/rat LC. The TCDD+EA group was treated with 0.5 mL/rat TCDD+0.5 mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen's testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effects.

Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin.

The aim of this study was to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cisplatin (CP)-induced testicular apoptosis in male rats. The control group was treated with placebo; LC, EA and CP groups were given alone LC, EA and CP, respectively; the CP+LC group was treated with a combination of CP and LC; and the CP+EA group was treated with a combination of CP and EA. Although CP significantly increased the number of Bax-positive (apoptotic) cells it had no effect on the number of Bcl-2-positive (antiapoptotic) cells compared with the control group. Administration of CP caused significant increase in lipid peroxidation and nonsignificant decrease in superoxide dismutase (SOD) activity along with some histopathological lesions in testicular tissue. However, combined treatments of LC or EA in addition to CP tended to prevent the CP-induced testicular apoptosis, histopathological lesions and lipid peroxidation.

Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant-antioxidant balance, and protective roles of lycopene and ellagic acid.

In this study, the toxic effect of cyclophosphamide (CP) on sperm morphology, testicular histology and blood oxidant-antioxidant balance, and protective roles of lycopene (LC) and ellagic acid (EA) were investigated. For this purpose, 48 healthy, adult, male Sprague-Dawley rats were divided into six groups; eight animals in each group. The control group was treated with placebo. LC, EA and CP groups were given alone LC (10 mg/kg/every other day), EA (2 mg/kg/every other day) and CP (15 mg/kg/week) respectively. One of the last two groups received CP + LC, and the other treated with CP + EA. All treatments were maintained for 8 weeks. At the end of the treatment period, morphological abnormalities of sperm, plasma malondialdehyde (MDA) levels and glutathione (GSH) levels, and GSH-peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities in erythrocytes, and testicular histopathological changes were examined. CP administration caused statistically significant increases in tail and total abnormality of sperm, plasma MDA level and erythrocyte SOD activity, and decreases in erythrocyte CAT activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's Testicular Score along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue. However, LC or EA treatments to CP-treated rats markedly improved the CP-induced lipid peroxidation, and normalized sperm morphology and testicular histopathology. In conclusion, CP-induced lipid peroxidation leads to the structural damages in spermatozoa and testicular tissue of rats, and also LC or EA have a protective effect on these types of damage.

Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis.

The present study was conducted to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cyclophosphamide (CP)-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. Forty-eight healthy adult male Sprague-Dawley rats were divided into six groups of eight rats each. The control group was treated with placebo; the LC, EA and CP groups were given LC (10 mg kg(-1)), EA (2 mg kg(-1)) and CP (15 mg kg(-1)), respectively, alone; the CP+LC group was treated with a combination of CP (15 mg kg(-1)) and LC (10 mg kg(-1)); and the CP+EA group was treated with a combination of CP (15 mg kg(-1)) and EA (2 mg kg(-1)). All treatments were maintained for 8 weeks. At the end of the treatment period, bodyweight and the weight of the reproductive organs, sperm concentration and motility, testicular tissue lipid peroxidation, anti-oxidant enzyme activity and apoptosis (i.e. Bax and Bcl-2 proteins) were determined. Administration of CP resulted in significant decreases in epididymal sperm concentration and motility and significant increases in malondialdehyde levels. Although CP significantly increased the number of Bax-positive (apoptotic) cells, it had no effect on the number of Bcl-2-positive (anti-apoptotic) cells compared with the control group. However, combined treatment of rats with LC or EA in addition to CP prevented the development of CP-induced lipid peroxidation and sperm and testicular damage. In conclusion, CP-induced lipid peroxidation leads to structural and functional damage, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protect against the development of these detrimental effects.

Modulatory effects of lycopene and ellagic acid on reproductive dysfunction induced by polychlorinated biphenyl (Aroclor 1254) in male rats.

The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl-2 genes were investigated. AR administration caused statistically significant decreases in body-weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR-treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH-peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR-induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR-induced reproductive dysfunction in male rats.