Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Intracerebroventricular salusin-ß infusion to rats increases hypothalamus-pituitary-testicular axis hormones.

Salusin-ß (Sal-ß), which originates from preprosalusin, is a multifunctional hormone with a peptide structure. Sal-ß exists in the hypothalamus and can stimulate the pituitary gland. The present study was conducted to determine the effects of Sal-ß on hormones that play roles in the male reproductive system. Forty male Wistar Albino rats were used in the study. No infusions were performed on the control group, and infusions were applied to the infusion groups (artificial cerebrospinal fluid to the sham group, 2 and 20 nM Sal-ß to the experimental group) through intracerebroventricular infusion for 7 days at 10 µl/hour rate. The animals were decapitated after 7 days of infusion; and the hypothalamus, testicles, and blood tissue samples were collected. The gonadotropin-releasing hormone (GnRH) mRNA levels were determined from the hypothalamus tissues by using the Real Time-PCR Method, and the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were determined using the ELISA method. Also, Hematoxylin-Eosin Staining Method was used for histopathological evaluations in the testicle tissues. As a result, Sal-ß infusion increased GnRH mRNA levels in hypothalamus tissues (p < 0.05) besides, serum LH, FSH, and testosterone levels of the rats were higher at significant levels following Sal-ß infusion compared to the control and sham group (p < 0.05). In the histological examination of the testicle tissues, Sal-ß application was found to decrease the seminiferous tubule diameter and germinal epithelial thickness (p < 0.05). This evidence is the first, indicating that Sal-ß, which is administered to male rats with central infusion, stimulates hypothalamus and pituitary tissues, and causes increased secretion of male reproductive hormones.

Effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis in male rats.

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.

Protective effects of ghrelin on kidney tissue in rats with partial ureteral obstruction

Background/aim: The aim was to investigate the protective and therapeutic effects of ghrelin, which has antioxidant and antiinflammatory activity, on preventing kidney damage that occurs by induced partial ureteral obstruction in rats Materials and methods: Twenty-eight adult male rats were included in the study, and the rats were divided into 4 groups. After the laparotomy operation on the sham group, the ureter was identified in the retroperitoneal area and was duly sutured (n = 7). Ghrelin was administered for seven days intraperitoneally, and after the nephrectomy performed on the 15th day, the rats were sacrificed (n = 7). A partial ureteral obstruction was performed after the laparotomy on the PUO group. The rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). A partial ureteral obstruction was formed after the laparotomy followed by seven days of waiting in the PUO + ghrelin group. Ghrelin was given in the dose of 10 ng/kg per day intraperitoneally for the next 7 days, and the rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). All groups were evaluated for histological damage and catalase, superoxide dismutase, total glutathione, malondialdehyde, and myeloperoxidase levels were measured in the same tissues Results: When the 2nd group and the sham group were compared histologically, it was observed that the damage had increased by a statistically significant level in the partial ureteral obstruction group (P = 0.001). When the group which was ghrelin-treated after the partial ureteral obstruction was compared to the group with just partial ureteral obstruction, the histopathological changes were found to decrease significantly in that group (P = 0.001). While the statistical significance of the levels of CAT, GSH, and MPO enzymes was detected among biochemical changes in the 2nd group when compared to the sham group (P < 0.01), the 3rd group showed a statistically significant difference in the levels of SOD and GSH enzymes compared to the 4th group (P < 0.05). Conclusion: Ghrelin administration to rats after the formation of an experimental partial unilateral ureteral obstruction reduces tissue damage due to ghrelin's antiinflammatory and antioxidant effects. Ghrelin administration may prevent tissue damage biochemically and histopathologically in obstructive uropathy cases

Protective and therapeutic effects of dexpanthenol on isoproterenol-induced cardiac damage in rats.

The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO2 ), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase-3 were determined. BP and SO2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO-induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity.

Maternal viral mimetic administration at the beginning of fetal hypothalamic nuclei development accelerates puberty in female rat offspring.

This study aimed to investigate the effects of maternal viral infection during a critical time window of fetal hypothalamic development on timing of puberty in the female offspring. For that purpose, a viral mimetic (i.e., synthetic double-strand RNA, namely, polyinosinic-polycytidylic acid, poly (I:C)) or saline was injected (i.p.) to the pregnant rats during the beginning (day 12 of pregnancy, n = 5 for each group) or at the end of this time window (day 14 of pregnancy, n = 5 for each group). Four study groups were formed from the female pups (n = 9-10 pups/group). Following weaning of pups, vaginal opening and vaginal smearing was studied daily until 2 sequential estrous cycles were observed. During the second diestrus phase, blood samples were taken for progesterone, leptin, corticosterone, follicle-stimulating hormone, and luteinizing hormone. Maternal poly (I:C) injection on day 12 of pregnancy increased body mass and reduced the time to puberty in the female offspring. Neither poly (I:C) nor timing of injection affected other parameters studied (p > 0.05). It has been shown for the first time that maternal viral infection during the beginning of fetal hypothalamic development might hasten puberty by increasing body mass in rat offspring.

Histopathological and ophthalmoscopic evaluation of apocynin on experimental proliferative vitreoretinopathy in rabbit eyes.

The aim of the current study was to evaluate the effect of apocynin (APO) on the development of proliferative vitreoretinopathy (PVR). New Zealand-type male rabbits were randomly grouped into three as follows: (1) Sham group rabbits which were applied intraperitoneal (i.p.) vehicle without PVR; (2) PVR group rabbits where PVR was created and an i.p. vehicle was administered for 21 successive days; (3) PVR + APO group rabbits where PVR was created and i.p. APO was administered for 21 successive days. Fundus examination was conducted with an indirect ophthalmoscope before starting the experiments and at each visit afterwards. At the end of the work, the rabbits were sacrificed under high-dose anesthesia and then eye tissues were taken for histopathological analyses. In the PVR + APO group, histopathologic and ophthalmoscopic examination revealed significant decrease in PVR formation. As the result, it has been observed that APO at least partially inhibits PVR formation.

Melatonin's protective effect on the salivary gland against ionized radiation damage in rats.

OBJECTIVES: The aim of this study was to examine the effects of melatonin on ionized radiation-induced salivary gland damage using an experimental model. MATERIALS AND METHODS: Thirty-two rats were randomized into four groups: (i) the control group (C, n = 8) that received intraperitoneal (i.p.) 0.9% NaCl; (ii) the melatonin group (M, n = 8) that received i.p. 5 mg/kg melatonin; (iii) the radiotherapy group (RT, n = 8) that underwent irradiation; (iv) the melatonin plus radiotherapy group (M+RT, n = 8) that received i.p. 5 mg/kg of melatonin, followed by irradiation 30 min later; and (v) the radiotherapy plus melatonin group (RT+M, n = 8) that received irradiation followed by i.p. 5 mg/kg of melatonin 30 min later. The medications and irradiation were administered for 5 days and the salivary glands of the rats were excised 10 days later; the histopathological changes in the salivary glands were assessed and biochemical analyses were conducted (tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI)). RESULTS: Regardless of whether melatonin was administered before or after radiotherapy, melatonin decreased the radiation-induced parotid and submandibular histological damage. In addition, regardless of whether administration occurred before or after radiotherapy, melatonin decreased oxidative stress markers, such as MDA, TOS, and OSI. On the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin. CONCLUSIONS: Melatonin may have a significant protective effect on salivary gland damage secondary to ionizing radiation.

Is More Cortical Bone Decortication Effective on Guided Bone Augmentation?

This study aims to evaluate the possible effect of more cortical bone decortication (CBD) on guided bone augmentation. A total of 16 New Zealand rabbits and 32 titanium domes were used. No cortical bone decortication was applied to the control group and in the study groups, the cortical bones were decorticated with a round burr (Group A: 1 hole with bleeding, Group B: 5 holes with bleeding, Group C: a thin layer of compact bone was completely removed with no bleeding). Then 2 titanium domes were placed on the calvarium of each rabbit with hydroxyapatite/beta-tricalcium phosphate. After 3 months, the animals were sacrificed and specimens were sent for histological and histomorphometric analysis. Histological and histomorphometric analysis showed that bone decortication with burr significantly increased new bone regeneration in all the experimental groups compared with the control group (P <0.05). No statistically significant difference was determined between the study groups. In conclusion, CBD, which has no negative impact on surgery, has a positive effect on guided bone augmentation. However, a greater amount of CBD does not have a greater effect.

The protective effect of apocynin on testicular ischemia-reperfusion injury.

PURPOSE: We investigated the protective effect of the NADPH oxidase inhibitor apocynin on testicular damage induced by ischemia-reperfusion injury in rats. MATERIALS AND METHODS: A total of 32 rats were randomly divided into 4 groups. Controls underwent left scrotal exploration only. The 3 groups with ischemia-reperfusion underwent 4-hour torsion followed by 1-hour detorsion. The ischemia-reperfusion only group underwent left testicular torsion and detorsion. The ischemia-reperfusion plus saline group underwent left testicular torsion, received 10 ml/kg saline intraperitoneally at minute 210 of ischemia and then underwent detorsion. The ischemia-reperfusion plus apocynin group underwent left testicular torsion, received 20 mg/kg apocynin intraperitoneally at minute 210 of ischemia and then underwent detorsion. We determined histopathological findings and performed specific biochemical analyses. RESULTS: In the ischemia-reperfusion only and the ischemia-reperfusion plus saline groups malondialdehyde, total oxidative capacity and the oxidative stress index were significantly higher. Superoxide dismutase, catalase, glutathione peroxidase and glutathione were significantly lower. Apocynin significantly decreased malondialdehyde, total oxidative capacity and the oxidative stress index, and significantly increased superoxide dismutase and catalase. There was a significantly increase in the number of giant, degenerated and desquamated cells in the ischemia-reperfusion group. Apocynin significantly improved these histological alterations. CONCLUSIONS: These histopathological and biochemical findings show the beneficial effects of apocynin on testicular ischemia-reperfusion injury.

Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates.

Bacterial toxins are widespread in the environment as well as in the digestive system of humans and animals. Toxin from Gram-negative bacteria (endotoxin or lipopolysaccharide; LPS) has a life-long programming effect on reproduction in rats, but the mediators have not been well-documented, so we investigated the effects of LPS on the timing of puberty in female rats. Because the levels of nitric oxide (NO) and interleukin 1ß (IL-1ß) increase following injection of LPS, we injected neonates (post-natal day (pnd) 7) with LPS, with or without NO or IL-1ß inhibitors. Half of the prepubescent (pnd 30) animals received an additional LPS injection. Vaginal opening, number of ovarian follicles, and serum anti-LPS antibodies were determined. A single LPS injection was sufficient to reduce the primordial follicle pool, but puberty was delayed when rats received 2 LPS injections (at pnd 7 and 30). NO or IL-1ß inhibitors improved both of these parameters, suggesting that the early detrimental effects of LPS on puberty and primordial follicle pool are mediated by NO and IL-1ß.

The effect of dexmedetomidine against oxidative and tubular damage induced by renal ischemia reperfusion in rats.

Dexmedetomidine (dex) is a potent, highly selective and specific α2-adrenoreceptor agonist. This experimental study was designed to investigate protective and therapeutic effect of two different doses of dex, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Male Sprague-Dawley rats were divided into four groups, each including 10 animals: control group, ischemia-reperfusion (I/R) group; treated groups with 10 µg/kg of dex and 100 µg/kg of dex. After removing right kidney of the rats, the left kidney has performed ischemia during 40 min and reperfusion in the following 3 h. The histopathological findings, and also tissue superoxide dismutase (SOD) and catalase (CAT) enzyme activity, malondialdehyde (MDA), glutathione (GSH), serum blood urea nitrogen (BUN), creatinine (Cre) and tumor necrosis factor-alpha (TNF-α) levels were determined. In the I/R group, compared to the control group, levels of BUN, Cre and kidney tissue MDA have increased significantly, SOD, CAT enzyme activity and glutathione levels have decreased significantly. In the dex10 group, compared to the I/R group, levels of Cre and TNF-α have decreased significantly, while the SOD activity has increased significantly. In the dex100 group, compared to the I/R group, levels of BUN, Cre have decreased significantly, while the SOD activity has increased significantly. In the I/R group, there was also extensive tubular necrosis, glomerular damage in the histological evaluation. Dex ameliorated these histological damages in different amounts in two treatment groups. In this study, the protective effects of dex against renal I/R injury have been evaluated by two different amount of doses.

Comparison of the Effects of Low-Level Laser Therapy and Ozone Therapy on Bone Healing.

This study aims to compare the effect of low-level laser therapy (LLLT) and ozone therapy on the bone healing. Thirty-six adult male Wistar albino rats were used for this study. Monocortical defects were shaped in right femur of all rats. Defects were filled with nano-hydroxyapatite graft. The animals were divided into 3 groups and each group was than divided into 2 subgroups. Then, LLLT with a diode laser was applied to the first group (G1), ozone therapy was applied to the second group (G2), and no treatment was applied to the third group as a control group (G3). Animals were sacrificed after 4th and 8th weeks and the sections were examined to evaluate the density of the inflammation, the formation of connective tissue, the osteogenic potential, and osteocalcin activity. As a result, there were no significant differences among the groups of 4 weeks in terms of new bone formation. In the immunohistochemical assessment, the number of osteocalcin-positive cells was higher in the laser group compared to the other group of 4 weeks; this difference was statistically significant in the LLLT and ozone groups (P < 0.05). Histomorphometric assessment showed that the new bone areas were higher in the LLLT and ozone groups; furthermore, there was a statistically significant difference in the LLLT in comparison with the control group at 8th week (P < 0.05). At the same time immunohistochemical assessment showed that osteocalcin-positive cells were considerably higher in G2 than G1 at 8th week (P < 0.05). The findings of this study may be the result of differences in the number of treatment sessions. Further studies are therefore needed to determine the optimal treatment modality.

Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications.

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin.

BACKGROUND: Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor. OBJECTIVES: We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH. METHODS: The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 µg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed. RESULTS: Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it. CONCLUSION: ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.

The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (IR) injury of the liver may cause various types of damage to hepatic tissues. It can affect the prognosis of patients and the success of an operation. Dexmedetomidine is a selective α2 receptor agonist. We investigated whether dexmedetomidine provides protection against IR-induced liver injury in rats. METHODS: Forty rats were divided equally into four groups. In group 1, the liver was manipulated after the laparotomy, and no occlusion of the vessels of the liver was performed. In group 2, once the abdomen was opened, 60 min of ischemia and 60 min of reperfusion were applied according to the segmental hepatic ischemia model. In group 3, 10 µg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. In group 4, 100 µg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. Further procedures in groups 3 and 4 were the same as those of group 2. After the experiment was completed, the rats were killed. Liver tissues were removed and stored until biochemical and histologic assessments were performed. RESULTS: The malondialdehyde level in group 2 was higher than that of groups 1, 3, and 4 (P = 0.001, P = 0.000, and P = 0.000, respectively). Superoxide dismutase, catalase, and glutathione levels in group 2 were lower than those in group 1 (P = 0.001, P = 0.027, and P = 0.014, respectively). Superoxide dismutase and catalase levels in group 4 were higher than those in group 2 (P = 0.002 and P = 0.000, respectively). GSH levels in groups 3 and 4 were higher than those in group 2 (P = 0.049 and P = 0.006, respectively). A lower glutathione peroxidase level was detected in groups 2 and 3 than that in group 1 (P = 000). Group 4 demonstrated an increase in glutathione peroxidase levels compared with group 3 (P = 0.014). The histologic injury scores in groups 2-4 were higher than those in group 1 (P = 0.003, P = 0.002, and P = 0.001, respectively). However, the histologic injury scores were lower in groups 3 and 4 than those in group 2 (P = 0.003 and P = 0.002, respectively). CONCLUSIONS: This study showed that dexmedetomidine may protect the liver against IR injury in rats.

Effects of ozone therapy on cyclophosphamide-induced urinary bladder toxicity in rats.

PURPOSE: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC). METHODS: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples. RESULTS: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05). CONCLUSION: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.

Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats.

The objective of current study is to investigate the effects of the administration of chrysin (CH) and quercetin (Q) on rat liver in which oxidative and histological damage had been induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were randomly divided into six equal groups. TCDD was orally administered at the dose of 2 µg/kg/week, and Q and CH were orally administered at the doses of 20 mg/kg day and 50 mg/kg/day, respectively, by gavages dissolved in corn oil. The liver samples to be analyzed for the determination of oxidative and histological alternations were taken from rats at 60 days. The results indicated that although 2,3,7,8-TCDD significantly induced (P ≤ 0.01) lipid peroxidation (increase of MDA levels), it positively affected oxidant/antioxidant system (a decline in the levels of GSH, CAT, GSH-Px, and CuZn-SOD) in rats significantly. The histological changes observed in the liver correlated with the biochemical findings. However, these effects of TCDD on oxidative and histological changes were eliminated by Q and CH treatment. In conclusion, TCDD caused an adverse effect on rat's liver. When Q and CH were given together with TCDD, they prevented hepatotoxicty induced by TCDD. Thus, it is thought that Q and CH may be useful as a new category of anti-TCDD toxicity agent.

The effects of pentoxifylline and caffeic acid phenethyl ester on TNF-α and lung histopathology in D-galactosamine-induced pulmonary injury in rats.

In this study, we aimed to investigate the effects of pentoxifylline [PTX] and caffeic acid phenethyl ester [CAPE] in D-galactosamine [D-GAL]-induced pulmonary injury in rats. The rats were randomly divided into six groups: control, D-GAL, D-GAL+PTX, D-GAL+CAPE, PTX and CAPE. Each group included eight animals. Lung sections from the control, PTX and CAPE groups had a normal histological appearance. The D-GAL group showed histopathological changes in lung tissue, including haemorrhage, oedema, inter-alveolar septal thickening and widespread infiltration of inflammatory lymphocytes and macrophages. Administration of PTX and CAPE significantly reduced histopathological damage scores in the D-GAL+PTX and D-GAL+CAPE groups compared with the D-GAL group. PTX and CAPE treatment also significantly decreased malondialdehyde levels, increased levels of reduced GSH and increased catalase and superoxide dismutase activity in lung tissue samples. These results indicate that the destructive effects of D-GAL-induced inflammation in the rat lung are significantly reduced following administration of PTX and CAPE.