Efsun Kolatan

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.

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.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity

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.

Pioglitazone Reduces Peritoneal Fibrosis via Inhibition of TGF-β, MMP-2, and MMP-9 in a Model of Encapsulating Peritoneal Sclerosis

Abstract Objective: Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) 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-β, 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-β activities. Conclusion: Pio, via MMP and TGF-β 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.

Protective effects of topiramate against hyperoxic brain injury in the developing brain.

Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.

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-β 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-β 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).

Technetium-99m labeled Mebendazole and biodistribution in experimentally Trichinella spiralis-infected rats

The aim of this study was to localize the biodistribution of Technetium-99m (99mTc) Mebendazole in experimentally Trichinella spiralis (T. spiralis)-infected rats. Localizing and distinguishing the “T. spiralis” in body sites are very important and life saving processes. Scintigraphic detections may help to determine the sites of trichinellosis infection. Twelve healthy female Wistar rats were infected via oral administration of infected muscle containing 750 to 1000 larvae. In this study, the antibiotic was labeled with Tc-99m, and 99mTc-Mebendazole was assessed as an infection imaging agent in a rat model. 99mTc-mebendazole was examined for localizing the normal, and inflamed with trichinellosis in rat muscle tissues after administrated 99mTc-mebendazole via intravenous (IV) or oral gastric catheter, and also for differentiating them from each other. 99mTc labeled mebendazole was retained in infectious areas. It was established that 99mTc-mebendazole which was administrated via IV route has high organ restrain level. It was observed that 99mTc-mebendazole uptake was high in tongue and diaphragm muscles of T. spiralis-infected rats after administration of radiolabeled mebendazole via either oral or IV routes. This study may be viewed as a basement of future studies on diagnosis of T. spiralis infection.

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.

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 groups hearing thresholds deteriorated in all frequencies. The ITGD groups 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.