Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

Caution may be required in using l-theanine in diabetes mellitus: A study on the rats.

BACKGROUND: The study aimed to identify the effects of l-theanine on kidney and heart tissues in diabetic rats. 24 male rats included in the study were divided into 4 groups (n = 6/group): SHAM, LTEA, DM and DM + LTEA. For 28 days, drinking water was given to SHAM and DM, and LTEA (200 mg/kg/day) to LTEA and DM + LTEA groups, intragastrically. DM was induced by 120 mg/kg nicotinamide (NA) + 60 mg/kg streptozotocin (STZ). The levels of cystatin C (CysC) and angiotensin-converting enzyme 2 (ACE2) were determined by ELISA kits, homocysteine, electrolytes and iron by an autoanalyzer, the ratio of oxidized/total reduced glutathione (GSSG/TGSH) by assay kits. The tissues were histopathologically analyzed. RESULTS: LTEA alleviated histopathological degenerations. However, it decreased significantly serum iron and homocysteine levels (p < 0.05). CONCLUSION: LTEA did not exhibit significant protective effects on kidney and heart tissues; it may have affected the homocysteine and iron metabolisms in diabetics.

How does l-theanine treatment affect the levels of serum and hippocampal BDNF, insulin and adipocytokines in diabetic rats?

BACKGROUND: Diabetes Mellitus (DM), a metabolic disease characterized by the increased blood glucose level, insulin deficiency or ineffectiveness, may cause structural and functional disorders in the brain. l-Theanine (LTN) has the relaxing, psychoactive, antidepressant, anti-inflammatory and antinecrotic properties, and regulates the functions of hippocampus (HP) in brain. In the present study, the aim was to identify the effects LTN on the levels of BDNF, insulin and adipocytokines (TNF-α, leptin, adiponectin and resistin) in both HP and serum of diabetic rats. METHODS: 32 male Wistar rats were divided into four groups (n = 8/group): Control, LTN, DM and DM + LTN. Diabetes was induced by by nicotinamide/streptozotocin. 200 mg/kg/day LTN treatment was applied for 28 days. The serum and hippocampal levels of the parameters were determined by using commercial ELISA kits. Additionally, HP tissues examined histopathologically. RESULTS: LTN treatment significantly decreased leptin and adiponectin levels in HP tissues in diabetic rats (p < 0.05). Although it decreased the insulin level in both serum and HP, this was not statistically significant. No significant effect on other parameters was observed (p > 0.05). In histopathological analysis, although the damage was reduced by LTN in all sections of HP, this change was significant mainly in CA3 region (p < 0.05). CONCLUSION: It was concluded that LTN has the ability to reduce hippocampal degeneration and modulates adipocytokines in diabetic rats.

The value of endoplasmic reticulum stress markers (GRP78 and CHOP) in the diagnosis of acute mesenteric ischemia.

AIM: To evaluate levels of the endoplasmic reticulum (ER) stress markers GRP78 and CHOP in acute mesenteric ischemia (AMI) and to examine relations with degrees of AMI-related intestinal injury. MATERIALS AND METHODS: Twenty-four rats were divided into four groups. Group I and Group III represented the control groups, from which blood and tissue specimens were collected 2 and 6 h after laparotomy without superior mesenteric artery (SMA) ligation. Group II and Group IV constituted the ischemia groups, from which blood and tissue specimens were collected 2 and 6 h after SMA ligation. The ER stress markers GRP78 and CHOP, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) were investigated in each group. Ileum specimens were assessed in terms of ischemic injury, and appropriate comparisons were performed. RESULTS: Significantly higher GRP78, CHOP, TOS, and TAS values were determined in the ischemia groups (groups II and IV) compared to the control groups (groups I and III). This elevation was greater in the 6 h ischemia group, the group exposed to the greatest ischemic injury (Group IV). Significant and powerful correlation was present between histopathological damage and levels of the ER stress markers and oxidative markers. CONCLUSION: According to our results, ER stress markers (GRP78 and CHOP) increase significantly following ischemic injury. This elevation has the potential to be used diagnostically and also in prognostic terms due to the powerful correlation it exhibits with AMI-related ischemic injury.

A Comparison of the Effects of Grayanotoxin-Containing Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing.

OBJECTIVES: Delayed healing and non-union of fractures have a significant effect upon patient morbidity. Studies have therefore largely concentrated on accelerating fracture healing. This study was intended to compare the effect of "mad honey" and propolis on fracture healing using radiological and histopathological analysis. SUBJECTS AND METHODS: Femur fracture was surgically performed on 48 rats, followed by fixation. Animals were then divided into 8 groups: 2 control groups (15- and 30-day) and 6 treatment groups (15- and 30-day normal honey, 15- and 30-day "mad honey," and 15- and 30-day propolis). Rats were sacrificed at the end of these periods, and radiological and histological examinations were performed. RESULTS: Radiological healing in the propolis group after 15-day therapy was statistically better than in the control (p = 0.004) and normal honey (p = 0.006) groups. After 30-day therapy, healing in the propolis group (p = 0.005) and grayanotoxin-containing "mad honey" group (p = 0.007) were significantly better than in the control group. Histologically, there was a statistically significant difference between the 15-day propolis group and the other groups (control, honey, mad honey: p = 0.003, p = 0.003, and p = 0.002, respectively). We also found a statistically significant difference when the 30-day propolis group (p = 0.005) and "mad honey" group (p = 0.007) were compared to the control group. CONCLUSIONS: This study shows that grayanotoxin-containing "mad honey" and propolis can accelerate fracture healing.

Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction.

PURPOSE: Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP) due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction. MATERIAL AND METHODS: A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP). An animal model of bilateral cavernous nerve crush injury (BCNI) was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO) was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day) as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-ß1 (TGF-ß1) level. Penile corporal apoptosis was determined by TUNEL method. RESULTS: Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-ß1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats. CONCLUSIONS: Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-ß1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

The effect of ethyl pyruvate and N-acetylcysteine on ischemia-reperfusion injury in an experimental model of ischemic stroke.

INTRODUCTION: Reperfusion therapies play an important role in early-period treatment for patients presenting to the emergency department due to stroke. However, the ischemia-reperfusion injury that may occur with reperfusion must then be considered. The purpose of this study was to determine the effectiveness of N-acetylcysteine (NAC) and ethyl pyruvate in preventing ischemia-reperfusion injury. METHOD: This study is a randomized, controlled experimental study. In group 1, rats' left main carotid arteries were clamped. Reperfusion was established by releasing the clamp after 1.5 hours. In group 2, the left main carotid artery was clamped, and 20 mg/kg intraperitoneal NAC was administered after 1 hour. The clamp was released 0.5 hour after NAC administration. In group 3, rats' left carotid arteries were clamped, and 50 mg/kg ethyl pyruvate was administered intraperitoneally after 1 hour. The clamp was released 0.5 hour after ethyl pyruvate administration. All tissue samples were collected 2.5 hours after reperfusion. Brain tissues were compared histopathologically. RESULTS: A higher percentage of degenerative neurons was determined in group 1 compared with groups 2 and 3 (P values: P(a) = .003 and P(c) = .003, respectively). A significant difference was also observed between groups 2 and 3 (P(b) = .003), with the percentage of degenerative neurons being lower in the NAC group than in the ethyl pyruvate group. CONCLUSION: The use of NAC and ethyl pyruvate reduces injury resulting from ischemia-reperfusion in an experimental animal model of acute ischemic stroke and subsequent reperfusion.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism.

PURPOSE: To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. RESULTS: Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. CONCLUSIONS: The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

Diagnostic value of plasma signal peptide-Cub-Egf domain-containing protein-1 (SCUBE-1) in an experimental model of acute ischemic stroke.

OBJECTIVES: This study was intended to examine possible diagnostic value of plasma Signal Peptide-Cub-Egf domain-containing protein-1 (SCUBE1) levels in an experimental model of acute ischemic stroke. METHODS: Twenty-four female Sprague Dawley rats were divided into four groups. Blood and brain tissue specimens were collected immediately following artery ligation (control; Group 1), 1h after ligation (Group 2), 2 h after ligation (Group 3) and 6h after ligation (Group 4). SCUBE1 levels were investigated in the serum specimens. The brain samples were examined histopathologically. Correlation analysis was performed between the values. RESULTS: Median SCUBE1 values were 1.75 ng/ml in the control group, 3.80 ng/ml, 3.71 ng/ml and 4.19 ng/ml in the groups 2, 3 and 4, respectively (n=6 for each, P=0.004, for each group compared to control values). Histopathological analysis revealed median atrophic neuron percentages of 16% (in group 1), 42%, 55% and 76% in group 2, 3 and 4 respectively (n=6 for each, P=0.004, for each group compared to control group). A higly significant correlation was determined between SCUBE-1 levels and percentage of atrophic neurons (r=0.744 P=0.000). CONCLUSIONS: In this experimental model of acute ischemic stroke plasma SCUBE1 levels rose from the 1st hour of induced stroke and remained high up to 6th hour tested. Results of this experimental study has a potential to become the basis for a clinical study to confirm whether SCUBE1 can be used as a biomarker in the early diagnosis of acute ischemic stroke patients.

Protective effect of clotrimazole on lung injury in an experimental model of ruptured abdominal aortic aneurysm.

BACKGROUND: Lungs are the target organs most affected by ischemia/reperfusion (I/R) injury, which is exacerbated when hemorrhagic shock occurs. Suppressing various proinflammatory cytokines, inflammation and oxidation that initiate and aggravate lung damage with various drugs or methods provides significant benefits in preventing lung damage. OBJECTIVES: This study aims to evaluate the protective effect of clotrimazole (CLT), an antimycotic drug, on lung injury and systemic inflammatory response in rats by creating an experimental model of a ruptured abdominal aortic aneurysm (RAAA). MATERIAL AND METHODS: Thirty-six male Sprague Dawley rats were randomly divided into 5 groups: sham, sham+CLT, sham+polyethylene glycol (PEG), shock+ischemia/reperfusion (SIR), and SIR+CLT. Saline, CLT and PEG were administered in the sham groups without shock and I/R. The hemorrhagic shock was developed in SIR groups by drawing blood for 1 h to keep the mean arterial pressure at 50 mm Hg. After 60 min, the SIR+CLT group was given 20 mg/kg CLT; then, the aortic clamps were opened, and rats were left for 120 min of reperfusion. The blood taken to create hemorrhagic shock was returned in a controlled manner during this time. At the end of the reperfusion procedure, samples were taken for cytokine levels in serum and lung tissue and for other biochemical analyses. Blood gas, histopathological examination and wet/dry weight measurements were performed to assess lung injury. RESULTS: An increase was observed in all parameters in the SIR group compared to the sham group. In the SIR+CLT group, the serum myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), lung MPO values, histologically lung injury scores, and lung tissue wet/dry ratio were decreased significantly when compared to the SIR group (p < 0.05). CONCLUSIONS: These results indicate that CLT may reduce the systemic inflammatory response and lung injury due to shock and I/R in an experimental model of RAAA.

Gentisic acid attenuates 5-fluorouracil-induced ovotoxicity in rats via modulating Nrf2 signalling: An experimental approach.

5-Fluorouracil (5-FU) is the third most used chemotherapeutic in the world with its anticancer effect resulting from its potential to block DNA replication. Like other cytotoxic agents, 5-FU has side effects on healthy tissues, and the reproductive system is among the tissues most affected by these undesirable effects. Gentisic acid (GEA) is a secondary metabolite that is abundant in fruits, vegetables and spices and has antioxidant activity. This study was conducted to investigate the toxicity of 5-FU in rat ovarian tissue and to determine the therapeutic activity of GEA on ovotoxicity caused by 5-FU. The results showed that 5-FU caused histopathological findings by suppressing Nrf2 pathway and accordingly increasing oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis. However, GEA treatments after 5-FU application ameliorated 5-FU-induced ovotoxicity dose-dependently through activation of Nrf2 pathway. All these findings provided strong evidence supporting the hypothesis that GEA treatment may have therapeutic effects against 5-FU-induced ovarian damage. However, the beneficial effect of GEA use in eliminating ovarian damage in women after 5-FU chemotherapy should continue to be investigated with more detailed molecular studies.

Effects of quercetin on gentamicin-induced experimental testicular injury in rats.

The purpose of this study was to investigate the effects of gentamicin (GEN) on the testis and whether quercetin (QUE) has any protective effect. Twenty-four adult male Sprague-Dawley rats were divided into equal four groups: control (0.9% saline solution), GEN (80 mg∕kg GEN), QUE (50 mg∕kg QUE) and GEN+QUE (80 mg∕kg GEN + 50 mg∕kg QUE). Histopathological (HP) evaluation of testis was performed, epididymal sperm parameters were analyzed and oxidative status was evaluated. The use of QUE improved the HP findings, such as decrease in the germinal epithelial thickness in the testicular tissue of the GEN group, decrease in the Johnsen's tubular biopsy score (JTBS), increase in the rate of immature cell shedding tubules, and the apoptotic index (AI). In the GEN group, sperm count, and abnormal morphology increased compared to the control group; the viability and motility decreased according to the sperm analysis results. In the GEN+QUE group, QUE was found to improve sperm viability and morphology. In the GEN group, tissue malondialdehyde (MDA) levels increased while superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels decreased. Compared with the GEN+QUE group, it was found that the tissue MDA level decreased, while the levels of SOD, CAT and GPx increased. The results demonstrate that GEN impairs testicular structure and function, and QUE treatment can prevent this adverse effect.

How does colistin-induced nephropathy develop and can it be treated?

Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

Effects of resveratrol on methotrexate-induced testicular damage in rats.

This study investigated the probable protective effects of resveratrol (RES), an antioxidant, against methotrexate- (MTX-) induced testis damage. Twenty-four male Sprague Dawley rats were randomly divided into four groups: control, RES, MTX, and MTX + RES groups. Rats were sacrificed at the end of the experiment. Plasma and tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activity in tissue, testicular histopathological damage scores, and testicular and epididymal epithelial apoptotic index (AI) were evaluated. The MTX group had significantly higher plasma and tissue MDA levels and significantly lower SOD and CAT activity than those of the control group. In the MTX + RES group, plasma and tissue MDA levels decreased significantly and SOD activity rose significantly compared to the MTX group. The MTX group had significantly lower Johnsen's testicular biopsy score (JTBS) values than those of the control group. JTBS was significantly higher in the MTX + RES group than in the MTX group. AI increased in the testis and epididymis in the MTX group and significantly decreased in the MTX + RES group. Our results indicate that RES has protective effects against MTX-induced testis damage at the biochemical, histopathological, and apoptotic levels.

Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway.

Although cisplatin (CDDP) is an effective anticancer agent, the ovotoxicity that can occur in female patients limits its use. Oxidative stress (OS) and inflammation are known to contribute to CDDP-induced ovotoxicity. Vanillic acid (VA) is a dietary herbal secondary metabolite with high free radical scavenging activity. It was aimed to evaluate the therapeutic effects of VA against CDDP-induced ovotoxicity in rats in this study for the first time. Ovotoxicity was achieved with a single dose of CDDP (5 mg/kg) in female rats. The therapeutic effect of VA was evaluated with 3-day administration of two different doses (5 and 10 mg/kg). While OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were measured in tissue samples, the levels of reproductive hormones were determined in serum samples using colorimetric methods. The results showed that CDDP-induced nuclear factor erythroid 2-associated factor 2 (Nrf2) inhibition combined with increased OS, inflammation, ERS and apoptosis increased ovarian damage. VA treatments reversed these changes via activating Nrf2 pathway dose-dependently. In addition, histopathological findings also supported the biochemical results. VA may be a good therapeutic molecule candidate for CDDP-induced ovarian damage due to strong antioxidant and Nrf2 activator properties.

Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.

AIM: Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. RESULTS: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. CONCLUSION: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury in a rat ovarian-torsion model.

BACKGROUND/AIMS: To evaluate the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury in a rat ovarian-torsion model. METHODS: 32 Sprague-Dawley rats were randomly divided into four groups: (1) ischemia group (n = 8) in which only left adnexal torsion was performed for 2 h, but no treatment was given; (2) vehicle group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia polyethylene glycol (3% PEG, 1 ml, i.p.) was administered and a 24-hour reperfusion was continued; (3) clotrimazole group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia clotrimazole (30 mg/kg, i.p.) was administered and a 24-hour reperfusion was continued, and (4) control group (sham-operated, n = 6) in which no adnexal torsion and no treatment were given. The criteria for ovarian ischemia were follicular cell degeneration, vascular congestion, hemorrhage and infiltration by inflammatory cells. Each specimen was scored for each criterion (0, none; 1, mild; 2, moderate; 3, severe). RESULTS: Clotrimazole significantly decreased plasma levels of serum malondialdehyde, ischemia-modified albumin, and total oxidant status. CONCLUSION: This study showed the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury.

Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity.

OBJECTIVES: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. CONCLUSION: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities.

The effect of simvastatin on picrotoxin-induced seizure in mice.

OBJECTIVE: To study the effect of simvastatin on picrotoxin-induce seizures in mice in order to understand the impact of gabaergic system on neuronal cell death. METHODS: The study was held between July and September 2011, at the Karadeniz Technical University in Trabzon, Turkey. Balb/c mice weighting 20-40g were randomly selected and divided into five groups of six each. The first group was designated as control group; and the second as the picrotoxin (10mg/kg; intraperitoneal) alone group. The rest of the groups were administered simvastatin in dozes of 10, 20 and 40mg/kg respectively. Onset, number and duration of seizures, and death time were measured in mice for one hour. At the end of the study, the brain was removed from mice and normal and degenerative pyramidal neurons were counted in hippocampal CA1, CA2, CA3 region by light microscope. Using SPSS 17, Mann=Whitney U and Chi square and student-T tests were performed for statistical analysis. RESULTS: Simvastatin (10mg/kg) significantly decreased the number and duration of picrotoxin-induced seizures in mice. In addition, Simvastatin (10, 20, and 40mg/kg) significantly reduced the total number of abnormal pyramidal cells in CA1 and CA3 hippocampal regions compared to the picrotoxin-alone group. CONCLUSION: The effect of simvastatin on picrotoxin-induced seizures may be the result of increase in gabaergic activity and decrease in glutamatergic activity. More studies are needed to validate these results.

7,8-Dihydroxyflavone alleviates Endoplasmic Reticulum Stress in cafeteria diet-induced metabolic syndrome.

AIMS: Prolonged Endoplasmic Reticulum Stress (ERS) is involved in the pathogenesis of metabolic syndrome, including type-2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. There have been significant efforts to discover molecules to treat ERS and/or to ameliorate associate symptoms. In this study, we investigated the effect of 7,8-Dihydroxyflavone (7,8-DHF) on ERS in liver and pancreas tissues in a cafeteria (CAF) diet induced metabolic syndrome model. MAIN METHODS: Male C57BL/6 mice were fed CAF diet for 16 weeks and 7,8-DHF was administered intraperitoneally (5 mg/kg/day) for last four weeks. 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in liver and pancreas tissues, insulin and interleukin-1ß (IL-1ß) in serum were analyzed by ELISA method and serum biochemistry parameters were analyzed with autoanalyzer. GRP78 and CHOP gene expression levels were determined by qRT-PCR. In addition, histopathological analyzes were performed on liver and pancreas tissues. KEY FINDINGS: Findings revealed that CAF diet caused metabolic abnormalities, insulin resistance and inflammation in serum and triggered ERS in pancreas and liver tissues. 7,8-DHF treatment significantly reduced metabolic abnormalities by reducing serum biochemical parameters, HOMO-IR and IL-1ß levels. qRT-PCR and ELISA results indicated that 7,8-DHF treatment down-regulated GRP78 and CHOP expression and protein levels in the liver and GRP78 expression in pancreas. Efficiency of 7,8-DHF in these tissues was also demonstrated by histopathological tests. SIGNIFICANCE: In conclusion, CAF diet-induced metabolic syndrome model, 7,8-DHF suppressed ERS and ERS-induced metabolic disorders in both liver and pancreas. Therefore, 7,8-DHF may potentially be a novel therapeutic compound to ameliorate ERS and related metabolic symptoms.