Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats.

Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (α-GST), nuclear factor-κB (NF-κB), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of α-GST, MDA, NF-κB and of IL-1ß, TNF-α gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.

The Role of Melatonin in Oxidative Stress, DNA Damage, Apoptosis and Angiogenesis in Fetal Eye under Preeclampsia and Melatonin Deficiency Stress.

Aim: The aim of this study was to investigate the possible mechanisms of ocular damage induced by pinealectomy (PNX) and preeclampsia (PE), and to determine the cellular and molecular effects of melatonin treatment on oxidative stress, DNA damage, molecular chaperone responses, induction of apoptosis and angiogenesis in the fetal eye of both PNX and PNX+PE animals. Material and Methods: We analysed therapeutic potential of melatonin on fetal eye damage in PNX and PNX+PE animals using Malondialdehyde (MDA), Random Amplified Polymorphic DNA (RAPD), qRT-PCR and Western blot assays. Results: Our study presents three preliminary findings: (a) in fetal eye tissues, PNX and PNX+PE significantly induce oxidative damage to both DNA and protein contents, leading to a dramatic increase in caspase-dependent apoptotic signalling in both mitochondrial and death receptor pathways; (b) the same conditions trigger hypoxia biomarkers in addition to significant overexpression of HIF1-α, HIF1-ß, MMP9 and VEGF genes in the fetal eye; (c) finally, melatonin regulates not only the expression of genes encoding antioxidant enzymes and increase in DNA damage as well as lipid peroxidation but also limits programmed cell death processes in the fetal eye of PNX and PNX+PE animals . Furthermore, melatonin can relatively modulate genes in the HIF1 family, TNF-α and VEGF, thus acting as a direct anti-angiogenic molecule. In conclusion, both PNX and PNX+PE induce ocular damage at both cellular and molecular levels in fetal eye tissue of rats. Conclusion: Our results clearly indicate the potential of melatonin as a preventative therapeutic intervention for fetal ocular damage triggered by both PNX and PNX+PE.

Hyperbaric oxygen treatment ameliorates gentamicin-induced nephrotoxicity and expression of kidney injury molecule 1 in the rat model.

In recent years hyperbaric oxygen (HBO2) therapy has been considered as an effective method for the treatment of gentamicin (GM)-induced renal toxicity. However, the findings related to the use of HBO2 for GM toxicity are limited and contradictory. The aim of this study is to investigate the protective role of HBO2 on GM-induced nephrotoxicity. For this purpose, Wistar albino rats (n=28) were randomly divided into four equal groups: C, HBO2, GM and GM+HBO2. GM (100 mg/kg, ip) and HBO2 were applied over seven days. On the eighth day blood and kidney tissue samples were harvested. The albumin, creatinine, and urea levels were determined from serum samples. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) values were analyzed spectrophotometrically. The relative expression level of TNF-α, IL-1ß and Kim-1 gene were determined by qRT-PCR assays; histopathologic investigation was completed in kidney tissue samples. Serum urea, albumin and creatinine levels significantly increased in the GM group compared to the GM+HBO2 group. For antioxidant parameters the GM+HBO2 group was not statistically different from the C group but was significantly different compared with the GM group. TNF-α, IL-1ß and Kim-1 gene expression levels in the GM group were statistically increased compared to the GM+HBO2 group (p=0.015, p=0.024, p=0.004) respectively. Severe tubular necrosis, epithelial desquamation and mild peritubular hemorrhage were observed in the GM-administrated group, while HBO2 exposure ameliorated these alterations. In conclusion, HBO2 exposure may be defined as a potential method for the prevention of GM-induced renal toxicity.

Adalimumab mitigates ovarian ischemia-reperfusion injury in rats by regulating oxidative stress, apoptosis and resolution of inflammation.

AIM: Ovarian torsion is a rare but an important reason of acute lower abdominal pain in women and associated with serious morbidity and mortality, if not treated promptly. The aim of this study was to evaluate the effects of an antitumor necrosis factor-α antibody on ovarian torsion in a rat model of ischemia-reperfusion (I/R) injury. METHODS: Forty female Wistar Albino rats were used in the present study. The rats were randomly divided into four groups: group I (sham), group II (I/R), group III (I/R + isotonic saline) and group IV (I/R + adalimumab). The I/R model was induced by torsion of both ovaries. Immunohistochemical staining for interleukin-1ß (IL-1ß), nuclear factor-κB (NF-κB), and inducible nitric oxide synthase was performed. Tissue and serum oxidative stress markers in conjunction with apoptotic index (AI) with the terminal deoxynucleotidyl transferase dUTP nick end labeling method were also calculated. RESULTS: Tissue total oxidant status, oxidative stress index and nitric oxide values were significantly decreased, and tissue total antioxidant status was found to be increased in group IV. Inflammation, vascular congestion and hemorrhagia were significantly lower in adalimumab-treated group. Serum oxidative stress markers and tissue malondialdehyde levels did not differ in study groups. The AI was significantly increased in groups 2 and 3. Adalimumab treatment significantly decreased the AI. CONCLUSION: Adalimumab therapy in rats attenuated I/R induced ovarian injury, possibly suppressing inflammation, inhibiting oxidative stress, and altering apoptotic pathways.

Major Ozonated Autohemotherapy Preconditioning Ameliorates Kidney Ischemia-Reperfusion Injury.

Medical ozone has therapeutic properties as an antimicrobial, anti-inflammatory, modulator of antioxidant defense system. Major ozonated autohemotherapy (MOA) is a new therapeutic approach that is widely used in the treatment of many diseases. The objective of the present study was to determine whether preischemic application of MOA would attenuate renal ischemia-reperfusion injury (IRI) in rabbits. Twenty-four male New Zealand white rabbits were divided into four groups, each including six animals: (1) Sham-operated group, (2) Ozone group (the MOA group without IRI), (3) IR group (60 min ischemia followed by 24 h reperfusion), and (4) IR + MOA group (MOA group). The effects of MOA were examined by use of hematologic and biochemical parameters consisting of neutrophil to lymphocyte ratio (NLR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, the histopathological changes including the tubular brush border loss (TBBL), tubular cast (TC), tubular necrosis (TN), intertubular hemorrhage and congestion (IHC), dilatation of bowman space (DBS), and interstitial inflammatory cells infiltration (IECI) were evaluated. In the IR group, compared to the Sham group, biochemical parameters indicating oxidative stress, NLR, IL-6, TNF-α, IMA, TOS, and OSI have increased. MOA reduced inflammation and oxidative stress parameters. Although TAS values have decreased in the IR group and increased in the MOA-pretreated group, no significant changes in TAS values were detected between the IR and MOA groups. The total score was obtained by summing all the scores from morphological kidney damage markers. The total score has increased with IR damage when compared with the Sham group (13.83 ± 4.30 vs 1.51 ± 1.71; p = 0.002). But, the total score has decreased significantly after application of MOA (5.01 ± 1.49; p = 0.002; compared with the IR group). MOA preconditioning is effective in reducing tissue damage induced in kidney ischemia-reperfusion injury. The protective effect of MOA is mediated via reducing inflammatory response and regulating of reactive oxygen species (ROS). Renal histology also showed convincing evidence regarding MOA's protective nature against kidney injury induced renal ischemia-reperfusion. Consequently, MOA might be helpful in protecting the kidneys from IR-induced damage in humans, probably through the anti-inflammatory effect and reducing the total oxidant status.

Blood gas analyzer utility in evaluating oxygen kinetics of the aqueous humor.

PURPOSE: To measure the partial pressure of oxygen (PO2) and carbon dioxide (PCO2) and the pH of aqueous humor (AH) and arterial blood samples from rabbits using a blood gas analyzer. METHODS: Twenty New Zealand rabbits were anesthetized intramuscularly with ketamine and xylazine and were then allowed to breathe room air. Using a gas blood analyzer, arterial blood and AH samples were analyzed for PO2, PCO2, and pH. RESULTS: The mean arterial blood pressure was 87.14 ± 15.0 mmHg. The mean blood and AH PO2 were 95.18 ± 11.76 mmHg and 88.83 ± 9.92 mmHg, the mean blood and AH PCO2 were 25.86 ± 5.46 mmHg and 29.50 ± 5.36 mmHg, and the mean blood and AH pH were 7.38 ± 0.06 and 7.33 ± 0.09, respectively. CONCLUSIONS: The blood gas analyzer was easily employed to evaluate the aqueous humor in rabbits. When comparing the results of studies evaluating aqueous PO2, care should be taken to determine the methods used in these studies.

Blood gas analyzer utility in evaluating oxygen kinetics of the aqueous humor / Utilidade de um analisador sanguíneo de gás para a avaliação cinética do oxigênio no humor aquoso

Purpose: To measure the partial pressure of oxygen (PO2) and carbon dioxide (PCO2) and the pH of aqueous humor (AH) and arterial blood samples from rabbits using a blood gas analyzer. Methods: Twenty New Zealand rabbits were anesthetized intramuscularly with ketamine and xylazine and were then allowed to breathe room air. Using a gas blood analyzer, arterial blood and AH samples were analyzed for PO2, PCO2, and pH. Results: The mean arterial blood pressure was 87.14 ± 15.0 mmHg. The mean blood and AH PO2 were 95.18 ± 11.76 mmHg and 88.83 ± 9.92 mmHg, the mean blood and AH PCO2 were 25.86 ± 5.46 mmHg and 29.50 ± 5.36 mmHg, and the mean blood and AH pH were 7.38 ± 0.06 and 7.33 ± 0.09, respectively. Conclusion: Conclusions: The blood gas analyzer was easily employed to evaluate the aqueous humor in rabbits. When comparing the results of studies evaluating aqueous PO2, care should be taken to determine the methods used in these studies. .

Objetivo: Medir a pressão parcial de oxigênio (PO2) e dióxido de carbono (PCO2), e o pH de humor aquoso (AH) e de amostras de sangue arterial de coelhos. Método: Vinte coelhos New Zealand foram anestesiados por via intramuscular com cetamina e xilazina, em seguida, foram liberados a respirar o ar ambiente. Utilizando um analisador sanguíneo de gás, amostras de sangue arterial e AH foram analisadas para PO2, PCO2, e pH. Resultados: A pressão arterial média foi de 87,14 ± 15,0 mmHg. A PO2 média do sangue e AH foi 95,18 ± 11,76 mmHg e 88,83 ± 9,92 mmHg; a PCO2 média do sangue e AH foi de 25,86 ± 5,46 mmHg e 29,50 ± 5,36 mmHg; o pH médio do sangue e AH foi 7,38 ± 0,06 e 7,33 ± 0,09, respectivamente. Conclusões: O analisador de gases no sangue foi facilmente empregadas para avaliar o humor aquoso em coelhos. Quando se comparam os resultados de estudos que avaliaram PO2 do humor aquoso, deve ser tomado cuidado para determinar os métodos utilizados nestes estudos. .

The investigation of airway management capacity of v-gel and cobra-PLA in anaesthetised rabbits

PURPOSE: To evaluate the applicability and airway management capacity of v-gel(r) and Cobra PLA in rabbit anaesthesia during assisted (AV) or controlled ventilation (CV). METHODS: This study was carried out in 44 adult New Zealand white rabbit. Baseline arterial pH, PaCO2 and PaO2 values were recorded. Anaesthesia was induced with 5 mg/kg xylasine and 35 mg/kg ketamine HCI combination. AV rabbits were assigned as; control (CG-AV; n=5), LMA (LMA-AV; n=5), cobra PLA (PLA-AV; n=5) and v-gel (v-gelAV; n=5). Rabbits have CV were also assigned as; ET (ET-CV; n=6), LMA (LMA-CV; n=6), cobraPLA (PLA-CV; n=6) and v-gel (v-gelCV; n=6). All measurements were repeated 1st, 5th, 15th and 30th mins during anaesthesia. RESULTS: The less insertion time, number of attempt and complications are recorded in v-gel applied rabbits compared to other apparatus. For arterial pH values significant differences are recorded in especially at 15th and 30th min between groups of CV (p<0.005 or p<0.001). All groups had similar results with each other during anaesthesia for PaCO2 except for LMA-CV group. CONCLUSION: The v-gel may be used as airway device in rabbit anaesthesia undergoing AV or CV and also can be a suitable alternative to endotracheal tubes and laryngeal mask airway. .

Comparison of effects of sugammadex and neostigmine on QTc prolongation in rabbits under general anesthesia

PURPOSE: To compare the effects of sugammadex and neostigmine, used to antagonize the effects of rocuronium, on the QTc interval. METHODS: This study used 10 adult New Zealand white rabbits of 2.5-3.5 kg randomly divided into two groups: sugammadex group (Group S, n:5) and neostigmine group (Group N, n:5). For general anesthesia administering 2 mg/kg iv propofol and 1 mcg/kg iv fentanyl, 0.6 mg/kg iv rocuronium was given. Later to provide reliable airway for all experimental animals V-Gel Rabbit was inserted. The rabbits were manually ventilated by the same anesthetist. After the V-Gel Rabbit was inserted at 2, 5, 10, 20, 25, 27, 30 and 40 minutes measurements were repeated and recorded. At 25 minutes after induction Group N rabbits were given 0.05 mg/kg iv neostigmine + 0.01 mg/kg iv atropine. Group S were administered 2 mg/kg iv sugammadex. RESULTS: Comparing the QTc interval in the rabbits in Group S and Group N, in the 25th, 27th and 30th minute after muscle relaxant antagonist was administered the QTc interval in the neostigmine group rabbits was significantly increased (p<0.05). CONCLUSION: While sugammadex, administered to antagonize the effect of rocuronium, did not significantly affect the QTc interval, neostigmine+atropine proloned the QTc interval. .

Revealing the history of sheep domestication using retrovirus integrations.

The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their "retrotype" and morphological traits dispersed across Eurasia and Africa via separate migratory episodes. Relicts of the first migrations include the Mouflon, as well as breeds previously recognized as "primitive" on the basis of their morphology, such as the Orkney, Soay, and the Nordic short-tailed sheep now confined to the periphery of northwest Europe. A later migratory episode, involving sheep with improved production traits, shaped the great majority of present-day breeds. The ability to differentiate genetically primitive sheep from more modern breeds provides valuable insights into the history of sheep domestication.

Tylosin does not affect GnRH-induced LH secretion in rams.

The aim of this study was to investigate the effect of a therapeutic dose of Tylosin (Tylan 50) on gonadotropin releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion in sheep. A total of 10 mature rams were divided into two groups by balancing body weights (bw) and body condition scores. Five of the rams received 10mg/kg Tylosin intramuscularly (i.m., Tylosin group), while the other five were given placebo (Control group), for 5 days. On Day 5, all the rams were injected intravenously (i.v.) with the GnRH agonist Ovarelin at 0.1 microg/kg bw. Blood samples were collected at -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, and 270 min for measuring LH levels in the plasma. Three days after the cessation of Tylosin application (Day 8) the injection of GnRH was repeated at the same dose. Although LH secretion appeared to be lower on Day 8 compared to Day 5, there were no significant differences between the groups for the mean LH concentrations, total LH secretion, peak LH concentrations, timing of LH peak, duration of LH secretion, and LH secretions on Days 5 and 8. These results indicate the absence of a negative effect of a therapeutic dose of Tylosin on GnRH-induced LH secretion in rams.