Protective effect of short-term thymoquinone administration on the central nervous system in cisplatin-induced neurotoxicity.

OBJECTIVE: This study was performed to investigate the potential beneficial effects of thymoquinone (TQ) on brain tissue based on biochemical and histopathological analyses in cisplatin (CIS) treated rats with central nervous system (CNS) neurotoxicity. MATERIALS AND METHODS: The rats were randomly divided into 4 groups with 8 rats in each group (n:8). Group 1: (Control), saline was administered for 3 days at a volume of 0.5 ml per day intraperitoneal (i.p.). Group 2: (CIS Group), one dose of CIS was administered (7 mg/kg i.p.). Group 3: (TQ Group), TQ was given at a dose of 5 mg/kg per day for 3 days (i.p.). Group 4: (CIS+TQ Group), one dose of 7 mg/kg was initiated half an hour before administration of CIS and one dose of 5 mg/kg per day was administered TQ i.p. for 3 days. RESULTS: Malondialdehyde levels were found to be statistically significantly higher in the CIS group compared to the control group. Degenerative changes observed in the CIS+TQ group were found to be milder than in the CIS group. In the CIS+TQ group, a statistically significant decrease in the severity of caspase-3 immunoreactivity was found when compared to the CIS group. It was found that the severity of neurofilament immunoreactivity monitored in neuronal extensions was similar in all groups. In the CIS+TQ group, the severity of tau protein's immunoreactivity was similar to that of the CIS-group. CONCLUSIONS: According to the results obtained in our study, beneficial effects were obtained in reducing neurotoxicity with short-term TQ application in rats treated with CIS treatment.

Is there a new pathway relationship between melatonin and FEZ1 in experimental rat model of Alzheimer's disease?

Alzheimer's disease (AD) is a progressive neurodegenerative disease. This study was performed to determine the possible relationship between melatonin, which is known to play a role in the neuro-protective mechanism in AD, and fasciculation and elongation protein zeta 1 (FEZ1). Thirty male rats were included and separated into 3 groups (n = 10) as vehicle (artificial cerebrospinal fluid), streptozotocin (STZ) and STZ+melatonin (MLT). Two intracerebroventricular (icv) injections of 3 mg/kg STZ were made 48 hours apart. MLT injections were implemented for 14 days (ip; 10mg/kg/day). The Morris Water Maze (MWM) test was performed and rats were sacrificed to assess FEZ1 gene expression and protein levels from the hippocampus tissues and serum levels of noradrenaline (NA), dopamine and serotonin were determined from the blood samples. It was determined that the FEZ1/ß-actin protein ratio in the STZ group was significantly higher than that of the Vehicle group (p < 0.05) and in the MLT­administered group, the protein levels were decreased to the levels observed in the Vehicle group. Serum NA levels of STZ and STZ+MLT groups were found to be lower than those in the Vehicle group, while no difference was found regarding dopamine and serotonin levels. These findings show that reversal of increased FEZ1 levels in AD-induced rats with melatonin administration is the evidence of the effect of melatonin through FEZ1 in AD (Tab. 2, Fig. 5, Ref. 67). Keywords: FEZ1, Alzheimer's disease, melatonin, rat, microtubules, mitochondria.

Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats.

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia-reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (p < 0.01) and XO (p < 0.05) activities and elevated GSH (p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

Nitric oxide concentrations, estradiol-17ß progesterone ratio in follicular fluid, and COC quality with respect to perifollicular blood flow in cows.

The objectives were to investigate relationships among concentrations of nitric oxide (NO), estradiol 17 beta (E2), and progesterone (P4) in follicular fluids (FF), and quality of cumulus oocyte complexes (COCs) with respect to perifollicular blood flow (FBF). In Experiment I, follicles (138) were classified according to the presence or absence of FBF (assessed with transvaginal Doppler ultrasonography) and diameter of follicles (small, 2-4 mm; medium, 5-8 mm; and large, ≥9 mm). Concentrations of NO in FF did not differ significantly among these size categories. However, NO concentrations in FF with FBF (54.4 ± 7.4 µmol/l) were higher (P<0.05) than in those without FBF (36.6 ± 4.1 µmol/l). There was a positive correlation (r=0.30, P<0.05) between NO concentrations and the E2:P4 in FF. Rate of E2 active (E2:P4 ≥ 1) follicles were numerically 1.2 (0.8-1.8) times higher in follicles with FBF (38.1%) compared to those without FBF (25.0%). Moreover, rates of E2 active follicles were 6.1 (0.7-55.2) and 1.3 (0.1-17.3) times higher (P<0.06) in large (43.3%) and medium (14.3%) compared to small follicles (11.1%), respectively. In Experiment II, quality of COCs from 2 to 8 mm follicles, obtained by transvaginal ovum pick up (OPU), was investigated with respect to FBF. Odds ratio to obtain higher quality COCs from follicles with FBF (47.1%) was 3.3 (1.1-9.6) fold higher (P<0.05) compared to those from follicles without FBF (14.6%). In conclusion, E2:P4, and NO concentrations in FF, as well as FBF, could be used to determine the functionality of ovarian follicles in cows. Moreover, determination of FBF could be useful to predict quality of COCs in cattle.

In vitro antimicrobial and antioxidant activity of acetone and methanol extracts from Thymus leucotrichius (Lamiaceae).

BACKGROUND AND OBJECTIVES: Thymus species has been used as tonic and herbal tea, antiseptic, antitussive, carminative, antioxidant, anti-inflammatory and antimicrobial activities. The acetone and methanol extracts of Thymus (T.) leucotrichius (Labiatae/Lamiaceae) was examined for antimicrobial and antioxidant properties. MATERIALS AND METHODS: The antioxidant properties of acetone and methanol extracts of Thymus leucotrichius were investigated using 1,1-diphenyl-2-picrylhydrazyl (DPPH)/nitric oxide (NO) radical scavenging activity, reducing power and total phenolic substance analysis. Antibacterial, antiyeast and antifungal activity of the plant extracts were tested using the disc diffusion method. RESULTS AND DISCUSSION: Results showed that IC50 of Thymus leucotrichius acetone and methanol extracts that scavenged 50% of the DPPH radical in the medium was found to be 109.72 microg/ml, 43.53 microg/ml, respectively. It was found that IC50 of Thymus leucotrichius acetone and methanol extracts which scavenged 50% of the NO radical in the medium was 180.56 microg/ml, and 67.34 microg/ml, respectively. In the Thymus leucotrichius acetone and methanol extracts (1 mg), 35.64 microg and 51.78 microg pyrocatechol equivalents of phenols were detected, respectively. Neither acetone nor methanol extract possessed activity towards Proteus vulgaris, Rhodotorula rubra, Candida albicans, Aspergillus parasiticus and Aspergillus niger. Acetone extract was the most active on Bacillus cereus and Bacillus megaterium. The sentivity was also observed against towards Escherichia coli H7:O157, Kluvyeromyces fragilis and Fusarium proliferatum when acetone extract used. The methanol extract also displayed more or less similar inhibitory activity towards the test microorganisms. Kluvyeromyces fragilis was resistant to methanol extract of the species unlike acetone extracts of the species. However, the fungus Fusarium proliferatum was markedly inhibited by the methanol extract of test species at 1000 microg and above. Significant inhibitory activities of the two extracts were based upon the increasing dose-dependent level.

Changes in follicular blood flow and nitric oxide levels in follicular fluid during follicular deviation in cows.

Two experiments were conducted to test the hypothesis that there are dynamic changes in follicular blood flow during follicular deviation and that nitric oxide (NO) in follicular fluid (FF) plays a role in regulation of follicular blood flow. In Experiment I, follicular blood flow of the two largest follicles was monitored by using Power Doppler ultrasonography during follicular deviation in sixteen follicular waves during eight estrous cycles in eight cows. Blood flow did not differ (P>0.05) between the dominant follicle (DF) and the largest subordinate follicle (SF) until the beginning of the deviation of the follicular size, but was higher (P<0.05) in DF than in the largest SF one and two days after the beginning of diameter deviation in ovulatory (n=5) and atretic (n=11) waves; respectively. In Experiment II, FF was aspirated from DF and the largest SF on the day of diameter deviation (DF, n=6; SF, n=6) and two days later (DF, n=12; SF, n=9). Nitric oxide did not differ (P>0.05) between DF and the largest SF on the day of diameter deviation but, one or two days after observed diameter deviation NO concentrations were lower (P<0.01) in DF compared to the largest SF. On the day of diameter deviation and two days later E2 levels in FF were higher (P<0.01) in DF than in the largest SF. P4 concentrations in FF were higher (P<0.05) in DF than in the largest SF on the day of diameter deviation, but did not (P>0.05) differ two days later. E2/P4 ratio in FF was the same (P>0.05) in DF and the largest SF on the day of diameter deviation, but was higher (P<0.01) in DF than in the largest SF one or two days later. In conclusion, area of follicular blood flow of DF and the largest SF increased in parallel with follicular size during follicular deviation. Furthermore, there were relationships between changes in follicular blood flow, NO concentrations and E2/P4 ratio in FF following the beginning of diameter deviation in cattle.

In vitro antioxidant and antimicrobial assays of acetone extracts from Nepeta meyeri Bentham.

UNLABELLED: BACKGROUND AND OBJECTIVIES: Nepeta species are used as diuretic, diaphoretic, antitussive, antispasmodic, antiasthmatic, febrifuge, emmenagogue, sedative agents, insecticidal, acaricidal, antiviral, anti-inflammatory and antioxidant. Acetone extract of Nepeta meyeri (Labiatae) was screened for antioxidant and antimicrobial activities. MATERIALS AND METHODS: The antioxidant prop erties of the extract were investigated by using various methods established in vitro systems such as 1,1-diphenyl-2-picrylhydrazyl (DPPH)/nitric oxide (NO) radical scavenging activity. Reducing power and total phenolic substance analysis and also antimicrobial activity of acetone extract of Nepeta meyeri were tested against six gram negative, seven gram positive bacteria and the yeast strain using the disc diffusion method. RESULTS AND DISCUSSION: Acetone extract of the plant examined exhibited a significant concentration-dependent inhibition of DPPH and NO* radical. Furthermore, Nepeta meyeri showed very high reducing power. In DPPH radical and NO* scavenging assays the IC50 value of extract was 672.2 microg/ml and 165.32 microg/ml, respectively. The amounts of total phenolic compounds were also determined and 12.86 microg pyrocatechol equivalents of phenols were detected in the extract. The data obtained from these in vitro models clearly demonstrated antioxidant potential of acetone extract of Nepeta meyeri. The extract revealed antibacterial activity against all gram positive bacteria but not was active against gram negative bacteria.

Pathological, biochemical and haematological investigations on the protective effect of alpha-lipoic acid in experimental aflatoxin toxicosis in chicks.

1. The purpose of this study was to investigate the protective effect of alpha-lipoic acid (LA) on aflatoxin (AF) toxicosis in chicks. 2. Groups of 10 Ross PM3 chicks were given, for 21 d, no AF (C), 60 mg/kg/bwt of alpha-lipoic acid (LA), 150 ppb of aflatoxin (AF1), 150 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF1 + LA), 300 ppb of aflatoxin (AF2), and 300 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF2 + LA). Before the animals were killed, blood samples were drawn for haematological analysis, and then tissue samples were collected for histopathological investigation. Immunohistochemical staining was performed against inducible nitric oxide synthase (iNOS) and nitrotyrosine on liver samples. Apoptotic cell death in liver was assessed by in situ TUNEL assay. The malondialdehyde (MDA) and reduced glutathione (GSH) concentrations in liver and kidney were also determined. 3. Hydropic degeneration and occasional necrosis, bile duct hyperplasia and periportal fibrosis were observed in the livers of AF-treated groups. The severity of these changes was reduced in LA-supplemented AF groups. Occasionally, thymic cortical atrophy, lymphoid depletion in spleen and bursa of Fabricius, and degeneration in the kidney tubule epitheliums were detected in AF groups. The severity of these degenerative changes was slightly reduced in LA supplemented groups. 4. There was moderate to strong iNOS and nitrotyrosine immunoreactivity in the livers of AF groups, while decreased immunoreactivity was observed against both antibodies in the LA supplemented groups. Apoptotic cells were numerous in the AF groups, while greatly reduced in LA supplemented groups. 5. In the liver and kidney of AF-treated groups given 300 ppb of aflatoxin, MDA concentrations were increased as GSH decreased, compared to the control group. LA supplementation of AF-treated birds improved the results compared to the AF only groups, however a statistical difference was observed only in liver tissues between AF2 + LA and AF2 groups. Haematological variables showed no differences among the groups. 6. In conclusion, supplementation of feed with the antioxidant LA, might ameliorate the degenerative effects caused by aflatoxin due to lipid peroxidation.

Caffeic acid phenethyl ester prevents ovary ischemia/reperfusion injury in rabbits.

Protective effect of caffeic acid phenethyl ester (CAPE) on ovary ischemia/reperfusion (IR) injury was investigated in this study. Twenty four New Zealand rabbits were divided into 4 groups as follows: group S served as sham. Group C was intraperitoneally injected with CAPE (8.5mg/kg). In groups E+IR and C+IR, 1% ethanol and CAPE was given intraperitoneally before torsion, respectively. Then, the ovaries were subjected to IR in both groups. Ovary reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in group E+IR were significantly reduced compared to that of group S. GSH level and GSH-Px activity was significantly increased in group C+I/R. Thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity in group E+I/R was significantly higher than in group S. CAT activity was decreased to normal levels by CAPE treatment in group C+I/R, while TBARS in group C+IR was significantly reduced compared to that of E+IR. According to histopathological examination, severe congestion, hemorrhage, edema and leukocyte infiltration were observed in E+I/R group. CAPE prominently reduced degenerative effects of IR injury thus it alleviates free radical damage. In conclusion, CAPE which is able to prevent IR-induced injury in the ovaries may be of therapeutic value before the surgical correction.