Comparison of Cytotoxic and Ototoxic Effects of Lipoplatin and Cisplatin in Neuroblastoma In Vivo Tumor Model.

BACKGROUND: This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse neuroblastoma tumor model. METHODS: In this study, C1300 neuroblastoma cells were administered subcutaneously to 21 male nude mice. When the tumor reached 150 mm3 diameter, mice were randomized into 3 groups. Saline, cisplatin, and lipoplatin were given intraperitoneally. The auditory function tests were performed before administration and 72 hours after administration. Mice were sacrificed and the tumor and cochlea were removed after 72 hours. Histopathologic evaluation of necrosis and apoptosis was determined by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Cyclooxygenase 2, superoxide dismutase 2, and inducible nitric oxide synthase levels were determined by immunohistochemistry in tissue samples. RESULTS: Apoptosis and necrosis rates were higher in lipoplatin group than in cisplatin group (P=.035 and P=.010, respectively) in tumor tissue. In the spiral ganglion, apoptosis and necrosis were lower in the lipoplatin group than in cisplatin group (P=.002 and P=.002, respectively). Cyclooxygenase 2 pattern in the cochlea was positive in both control and lipoplatin group and negative in cisplatin group (P=.001). Superoxide dismutase 2 and inducible nitric oxide synthase 2 protein expressions showed no difference between groups. The auditory functions were similar to baseline values and had a better threshold value in lipoplatin group than cisplatin group. CONCLUSION: For the treatment of neuroblastoma, the use of lipoplatin seems to be beneficial in reducing side effects of cisplatin. We recommend that the mechanism of these properties of lipoplatin should be evaluated in further studies.

Effect of Korean Red Ginseng on Noise-Induced Hearing Loss.

OBJECTIVE: Noise-induced hearing loss (NIHL) is one of the most important problems affecting both social and professional life of patients. There is no treatment method considered to be successful on the hearing loss that has become a permanent nature. Aim of this study is to evaluate protective effect of Korean Red Ginseng (KRG) against NIHL in an animal model. METHODS: Twenty-eight rats were separated into four groups [control saline (group I), control KRG (group II), saline + noise (group III), KRG + noise (group IV)]. Rats in the saline and KRG groups were fed via oral gavage with a dose of 200 mg/kg/day throughout for 10 days. Fourteen rats (group III and IV) were exposed to 4 kHz octave band noise at 120 dB SPL for 5 hours. Hearing levels of rats were evaluated by distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) at 4, 8, 12, 16 and 32 kHz frequencies prior to and on days 1, 7 and 10 after the noise exposure. Rats were sacrificed on 10th day, after the last audiological test. Cochlea and spiral ganglion tissues were evaluated by light microscopy. RESULTS: Audiological and histological results demonstrated that after noise the group IV showed better results than group III. In the noise exposed groups, the most prominent damage was seen at the 8 kHz frequency region than other regions. After the noise exposure, DPOAE responses were lost in 1st, 7th and 10th measurements in both group III and IV. Thus, we were not able to perform any statistical analyses for DPOAE results. CONCLUSION: Our findings suggest that KRG seems to be an efficient agent against NIHL. There is need for additional research to find out about the mechanisms of KRG's protective effect.

Radiolabeling, In Vitro Cell Uptake, and In Vivo Photodynamic Therapy Potential of Targeted Mesoporous Silica Nanoparticles Containing Zinc Phthalocyanine.

Photodynamic therapy (PDT) is a noninvasive therapy based on the photodynamic effect. In this study, we sought to determine intracellular uptake and in vivo photodynamic therapy potential of Zn phthalocyanine-loaded mesoporous silica nanoparticles (MSNP5) against pancreatic cancer cells. MSNP5 were labeled with 131I; the radiolabeling efficiency was found to 95.5 ± 1.2% in pH 9 and 60 min reaction time. Besides, the highest intracellular uptake yields of 131I-MSNP5 nanoparticles in MIA PaCa-2, AsPC-1, and PANC-1 cells were determined as 43.9 ± 3.8%, 41.8 ± 0.2%, and 37.9 ± 1.3%, respectively, at 24 h incubation time. In vivo PDT studies were performed with subcutaneous xenograft cancer model nude mice with AsPC-1 pancreatic cancer cells. For photodynamic therapy, 685 nm red laser light 100 J/cm2 light dose using and 5-20 µM ZnPc containing MSNP5 concentrations were applied. Histopathological studies revealed that the ratio of necrosis in tumor tissue was higher in the treatment group than the control groups.

Cochlear and Vestibular Effects of Combined Intratympanic Gentamicin and Dexamethasone.

OBJECTIVE: The aim of this study is to evaluate the effects of an intratympanic gentamicin-dexamethasone combination on the inner ear. MATERIALS AND METHODS: Twenty-six Wistar albino rats were divided into four groups: Group I (Control), group II (Intratympanic dexamethasone; ITD), group III (Intratympanic gentamicin; ITG), and group IV (Intratympanic gentamicin and dexamethasone; ITGD). On the first day after basal auditory brainstem response (ABR) measurements, the ITG group received 0.03 mL of intratympanic gentamicin (26.7 mg/mL). Intratympanic injection of 0.06 mL of a solution containing 13.35 mg/mL gentamicin and 2 mg/mL dexamethasone was performed in the ITGD group. 0.03 mL of physiological intratympanic serum and dexamethasone (4 mg/mL) was applied in control and ITD groups, respectively. On the 7th day, ABR measurements were repeated and vestibular functions were evaluated. On the 21th day, ABR and vestibular tests were repeated, and the animals were sacrificed for histopathological investigation. RESULTS: The ITG group's hearing thresholds deteriorated in all frequencies. The ITGD group's hearing thresholds were significantly better than the ITG group, except at 8 kHz on the 7th day and in all frequencies at the 21th day measurements. The vestibular function scores of the ITG and ITGD groups were higher than the controls. Apoptotic changes were seen in cochlea, spiral ganglion, and vestibule of the ITG group. Cochlear and vestibular structures were well preserved in the ITGD group, similar to the controls. CONCLUSION: The ITGD combination led to a significant hearing preservation. Although in subjective vestibular tests, it seemed that vestibulotoxicity was present in both ITG and ITGD groups the histopathological investigations revealed no signs of vestibulotoxicity in the ITGD group in contrast to the ITG group. Further studies using a combination of different concentrations of gentamicin and dexamethasone are needed.

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS: In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem. CONCLUSION: KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.

Protective Effect of Acetyl-L-Carnitine Against Doxorubicin-induced Cardiotoxicity in Wistar Albino Rats.

BACKGROUND AND AIMS: Anthracyclines are one of the most preferred agents in practical pediatric oncology despite their dose-dependent cardiotoxic effects. The aim of this study was to investigate whether or not acetyl-L-carnitine (ALCAR) has protective effects on doxorubicin (DOX)-induced cardiotoxicity. METHODS: Wistar rats were divided into four groups; control, DOX, ALCAR and ALCAR+DOX. Rats in the first group were given saline on study days, whereas those in the second group were given a single dose of DOX on the 5th day and saline on the other days. Rats in the third group were given ALCAR and those in the fourth group were given ALCAR on study days but also given only a single dose of DOX on the fifth day of the study. Ejection fractions (EF) were measured by echocardiography before and after drug administration. Heart tissues were evaluated by light and electron microscopy. Apoptotic cells were determined with TUNEL and caspase-3 staining. RESULTS: DOX significantly decreased the EF values, whereas ALCAR did not. Cardiac functions were higher in the ALCAR+DOX group when compared to the DOX group. DOX administration caused a cardiac injury not only functionally, but also structurally, whereas ALCAR prevented it. CONCLUSIONS: ALCAR has a capacity of preventing DOX-induced cardiac injury at both functional and structural levels.

Effect of bevacizumab, a vascular endothelial growth factor inhibitor, on a rat model of peritoneal sclerosis.

PURPOSE: Peritoneal fibrosis is almost uniform feature encountered in peritoneal dialysis patients. The transition of epithelial cells to mesenchymal phenotype, neovascularization, and consequently development of peritoneal fibrosis occur due to the involvement of peritoneal membrane by various insults such as uremia itself, peritonitis attacks, and exposure to bio-incompatible peritoneal dialysis fluids. Bevacizumab is a monoclonal antihuman antibody developed against vascular endothelial growth factor and can reduce fibrosis by preventing neovascularization. There has been no study so far that demonstrates the effect of bevacizumab on peritoneal fibrosis in a rat model. METHODS: A total of 41 female Wistar albino rats were divided into six groups. The control group (C) received 0.9 % isotonic saline (2 ml/day) intraperitoneally (i.p) for 21 days. Chlorhexidine group (CH) received 15 % ethyl alcohol and 0.1 % chlorhexidine gluconate (CG) in saline (2 ml/day) i.p for 21 days. The resting group (R) received CG 2 ml/day i.p for 21 days. The bevacizumab-1 group (B1) received CG 2 ml/day i.p for 21 days and bevacizumab 2.5 mg/kg i.p as a single dose on day 21. The bevacizumab-2 group (B2) received CG 2 ml/day for 21 days and bevacizumab 2.5 mg/kg i.p on day 0 and day 21. The bevacizumab-3 group (B3) received bevacizumab 2.5 mg/kg i.p on day 0 and day 21. Peritoneal samples were taken from the left anterior abdominal wall. The thickness, vascularization, and fibrosis scores in the peritoneal samples were assessed using a light microscope. RESULTS: On histopathological evaluations, peritoneum thicknesses, vascularization scores, and fibrosis significantly decreased in bevacizumab groups B1 and B2. CONCLUSION: Histopathologically, bevacizumab was proven to attenuate fibrotic process in experimental peritoneal sclerosis model.

Is there a gender-related susceptibility for cisplatin ototoxicity?

Ototoxicity is a well-known side effect of cisplatin. Some genetic and non-genetic risk factors were described for cisplatin ototoxicity. Although there are some studies which point out a sex-related difference for cisplatin nephrotoxicity and neurotoxicity, sex-related differences for cisplatin ototoxicity have not been studied. The aim of this study is to reveal whether there is any gender-related difference for susceptibility to cisplatin ototoxicity in rats. Fourteen male, 14 female Wistar albino rats were divided into four groups; a female control, a male control, a female cisplatin and a male cisplatin group. Distortion Product Otoacoustic Emission and, Auditory Brainstem Response measurements were obtained. For the cisplatin groups 16 mg/kg of cisplatin was applied. On the 4th day audiological examinations were repeated. After killing, cochleae and brainstem tissues were evaluated by light and electron microscopy. The hearing of the female rat cisplatin group was found to have deteriorated more than the hearing of the male rat cisplatin group. Histopathological evaluation revealed more serious damage in the spiral ganglion and brainstem tissues of female rats. Hearing of female rats deteriorated more than the hearing of male rats upon application of cisplatin. This difference in hearing can be attributed to the more severe damage seen in neuronal tissues such as spiral ganglion cells and brainstem neurons.

Effect of erythropoietin on acoustically traumatized rat cochlea: an immunohistochemical study.

OBJECTIVE: To investigate the audiological and histopathological effects of erythropoietin on acoustic overstimulation in rats. STUDY DESIGN: Twenty-two male Wistar albino rats were divided into 3 groups: sham group (n = 7), erythropoietin injection group (n = 8), and saline injection group (n = 7). Both erythropoietin and saline injection groups were exposed to white noise (100 decibel [dB] sound pressure level [SPL]) for 3 hours. Auditory brainstem responses were measured before, immediately after, and on the 7th day of noise exposure. All animals were sacrificed on the 7th day and temporal bones were collected. The serial sections of the cochleae were stained by caspase-3 and caspase-9 immunostaining and by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method in order to detect apoptotic cells. RESULTS: In the saline group statistically significant differences were detected between the baseline and immediate postacoustic overstimulation thresholds of click and 6 kHz stimuli. However, when the baseline and immediate postacoustic overstimulation thresholds of click and 6 kHz stimuli were compared in the erythropoietin injection group, no statistically significant difference was determined. Histopathologic evaluations demonstrated that erythropoietin decreased the amount of apoptotic cells in the cochlea. CONCLUSION: Erythropoietin is likely to prevent the acute threshold changes and decrease the amount of apoptosis in cochlea after acoustic overstimulation in rats.

The effects of preoperative immunosuppressive therapy on ischemia and reperfusion (I/R) injury in healthy rats.

PURPOSE: Warm-ischemia-induced injuries might be encountered during renal transplants from cadavers and healthy donors. Toll-like receptors (TLR) in ischemia-reperfusion (I/R) injury are one of the indicators of intracellular injury pathways. The intensity of ischemic injury is directly proportionate to high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels on rats, which were pretreated with tacrolimus (FK506) before I/R. METHODS: Eight Wistar albino rats in the study group were administered .01 mg/kg intramuscular tacrolimus. Administration to the study group was performed 24 and 1 h before warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of distilled water. Blood samples were collected from the tail veins of all the rats on the first, second and third days. Expression levels of TLR2 and TLR4 genes were analyzed using the polymerase chain reaction method, to determine any significant difference between the control and study groups on the days when blood was taken. RESULTS: TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the study group were found to be statistically, and significantly, lower than those in the control group, on the second day following warm-ischemia- and reperfusion-induced injury. CONCLUSIONS: Administration of immunosuppressive drugs to healthy donor rats led to a statistically significant reduction in the expression levels of TLR2 and TLR4 in the early period. In light of the data obtained by this study, we hypothesize that a preoperative therapy on donors might have a role in preventing I/R injury.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity.

OBJECTIVES/HYPOTHESIS: Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem. STUDY DESIGN: In vivo study using an animal model. METHODS: Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem. RESULTS: In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly. CONCLUSIONS: Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.

Otoprotective effect of recombinant erythropoietin in a model of newborn hypoxic-ischemic encephalopathy.

OBJECTIVE: The aim of this study is to test the hypotheses that central auditory pathology as well as inner ear pathology is contributing mechanisms to observed hypoxic-ischemic encephalopathy (HIE) induced hearing loss and that recombinant erythropoietin (rhEPO) will reduce this cellular pathology and attenuate hearing loss. METHODS: Twenty-eight 7-day Wistar albino rat pups were divided into four groups: Control group (n=8) was given only intraperitoneal saline solution. Sham group (n=5) had only a midline neck incisions without carotid ligation under general anesthesia and administration of intraperitoneal saline solution. HIE group (n=8) and rhEPO treated group (n=7) were subjected to left common carotid artery ligation followed by 2.5h hypoxia exposure to a mixture of 8% oxygen and 92% pure nitrogen. HIE group was injected with intraperitoneal saline solution, while the rhEPO treated group received rhEPO 100 U/kg within the same volume as the saline-alone solution. At the end of the seventh week of age hearing (ABRs) was evaluated in response to clicks, 6 kHz and 8 kHz tone burst stimuli. Animals were sacrificed and both temporal lobes, cochleas and brainstems of the animals were collected. Tissue samples were evaluated with light microscopy, immunohistochemical studies, including TUNEL and caspase-3 stainings, and electron microscopy. RESULTS: Hearing thresholds were elevated in HIE animals. In rhEPO treated animals, ABR values were similar to controls. HIE caused apoptotic changes in brainstem structures as shown by light microscopy and immunohistochemical methods. Apoptotic changes also were found within the organ of Corti, spiral ganglion cells and neurons of temporal lobe by electron microscopic investigation. In rhEPO animals many of these apoptotic changes were observed, but reduced compared to untreated animals. CONCLUSIONS: Mechanisms underlying HIE-induced hearing loss are based on apoptosis in inner ear; however central auditory pathway pathology occurs as well, likely contributing to changes in auditory processing and perception of complex signals not reflected by the ABR threshold shifts. For both clinical and basic significance 'rhRPO' is found to reduce those effects.

Pioglitazone reduces peritoneal fibrosis via inhibition of TGF-ß, MMP-2, and MMP-9 in a model of encapsulating peritoneal sclerosis.

OBJECTIVE: Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-ß) were increased in peritoneal dialysis patients with encapsulating peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are the major regulators of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The objective of this study was to investigate the effect of pioglitazone (Pio), a synthetic PPAR-γ ligand, on the development of peritoneal fibrosis in CG-induced EPS rats. METHODS: Thirty-two Wistar albino rats were intraperitoneally injected with saline (C group n = 8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was administered orally to another group of CG injected rats (the CG + Pio group, n = 8) and to another control group (Pio group, n = 8) from initiation to the end of this study. After 14 days of Pio administration, the rats were killed and the parietal and visceral peritoneum were harvested. TGF-ß, MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a morphological examination of the peritoneal tissues were performed. RESULTS: Pio significantly inhibited thickening of the submesothelial layer, fibrosis, and inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP-9, TIMP-1, and TGF-ß activities. CONCLUSION: Pio, via MMP and TGF-ß inhibition, may lessen accumulation of peritoneal extracellular matrix and fibrosis to some extent in an EPS model and might be a new approach to the amelioration of EPS.

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin ototoxicity and neurotoxicity.

INTRODUCTION: Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent for pediatric tumors, and ototoxicity is one of the dose-limiting side effects. OBJECTIVE: It was the aim of our study to investigate the effect of acetyl L-carnitine (ALCAR) on experimental CDDP ototoxicity by audiologic tests, histomorphologic, immunohistochemical and ultrastructural examinations and to investigate the apoptotic pathways. MATERIALS AND METHODS: Wistar albino rats (n = 28) were studied. Baseline audiological tests were performed in 4 groups: group 1, control; group 2, ALCAR; group 3, CDDP; group 4, CDDP + ALCAR-administered rats. Control audiological tests were performed on the 3rd day, and then the rats were sacrificed. Ear and brain specimens were examined by transmission electron microscopy, and caspase 3, 8 and 9 activities were investigated. RESULTS: The CDDP-administered rats showed significant auditory brainstem response threshold shifts using all stimuli (clicks, 6-kHz and 8-kHz tone burst) compared with the control groups. The CDDP + ALCAR-administered rats showed significant auditory brainstem response threshold shifts by only click stimuli compared with the control groups. In the brain, spiral ganglion and organ of Corti, ultrastructural damage was prominent in group 3; the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase 3, 8 and 9 immunostaining cells was significantly high in group 3. CONCLUSION: ALCAR improves CDDP-induced auditory impairment, and also antioxidative and antiapoptotic properties of ALCAR on CDDP ototoxicity were supported by the findings.

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis.

RATIONAL: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. OBJECTIVES: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. MAIN FINDINGS: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-ß were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. PRINCIPAL CONCLUSIONS: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-ß in dialysate may be one of the possible underlying mechanisms.

Decrease in cell proliferation by an matrix metalloproteinase inhibitor, doxycycline, in a model of immune-complex nephritis.

AIM: Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN). METHODS: The induction of immune-complex glomerulonephritis was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund's adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days. RESULTS: Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN. CONCLUSION: Doxycycline, in addition to its antibiotic property, may, following further investigation, provide a possible survival benefit in proliferative glomerulonephritis.

Comparison of efficacy of ivermectin and doramectin against mange mite (Sarcoptes scabiei) in naturally infested rabbits in Turkey.

The authors used 14 New Zealand rabbits (5 naturally infested rabbits and 9 in-contact rabbits) for Sarcoptes scabiei treatment in this study. Signs, such as itchy ears, eyes, tail and abdominal skin, alopecia and pyoderma, were considered to be the cause of these disorders. Infested rabbits were grouped according to the intensity of S. scabiei infestation (low, medium and high). Each group was then divided into two subgroups; in one subgroup the rabbits received ivermectin (1%) and, in the other, doramectin (1%). All subgroups received a subcutaneous injection at a dosage of 400 microg/kg body weight every 80 h on three occasions. On day 28 after commencing the treatment, all the rabbits in the first two groups had recovered completely. Although both drugs were applied at the same time and at the same dose, the third group (high degree of infestation), revealed, both microscopically and macroscopically, that ivermectin has more rapid effect than doramectin. Treatment was effective in all groups.

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

BACKGROUND/AIMS: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. METHODS: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. RESULTS: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. CONCLUSIONS: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

Ghrelin may attenuate proinflammatory cytokine-mediated neuropathic pain.

Nerve damage that affects peripheral or central nerve systems leads to abnormal pain states referred to as neuropathic pain. The precise mechanisms in neuropathic pain are very complex, since they are thought to originate through multiple pathophysiological processes. There is quite evidence implicating the proinflammatory cytokines in the induction and facilitation of neuropathic pain. This pain syndrome is usually poorly controlled by available medications. Ghrelin, a peptide hormone predominantly secreted from the stomach, is an endogenous ligand to the growth hormone secretagogue receptor. Previous studies showed that ghrelin has potent anti-inflammatory effect; inhibiting proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Furthermore, there are recent studies which prove the interaction between ghrelin and the systems that play role in pain modulation. Therefore, we hypothesize that ghrelin might ameliorate neuropathic pain by diminishing the proinflammatory cytokines and also regulating pain system.