High prevalence of diabetes in elderly of Iran: an urgent public health issue.

Purpose: To determine the distribution of blood glucose and prevalence of diabetes in people above 60 years living in Tehran and their relationship with some variables. Methods: In this cross-sectional population-based study, multistage cluster sampling was performed in the over 60-year-old population of Tehran. Blood samples were collected from all participants and the data of the history of diabetes and the use of blood glucose lowering agents or other drugs were collected using interviews. Results: Of 3791 selected subjects, 3310 participated in the study (response rate = 87.3%). The mean blood Sugar (BS) and hemoglobin A1c (HbA1c) of the patients was 118.11(95% CI: 115.34 -120.88) and 6.12(95% CI: 6.05-6.2) respectively. The prevalence of diabetes was 29.03%(95% CI: 27.12-30.94) in all subjects, 26.83%(95% CI: 24.58-29.07) in men, and 31.2%(95% CI: 28.24-34.16) in women. Odds of diabetes was significantly worse in women. systolic blood pressure, diasstolic blood pressure, height, weight, waist circumference, wrist circumference, hip circumference, neck circumference and body mass Index were significantly higher in diabetic after adjusting for the effect of sex and age. The odds of blindness was 2.69 (95% CI: 1.10-6.59) times higher in diabetic than in non-diabetics. Conclusions: On average, one in every three persons above 60 years of age was diabetic. Therefore, attention should be paid to this age group, especially women, due the higher prevalence of diabetes. All anthropometric measurements except height had a strong correlation with diabetes. Blindness was significantly more in diabetics.

Dynamic corneal biomechanics in different cell layers: in keratoconus and normal eyes.

PURPOSE: This study aimed to determine the relationship between corneal cellular structures and biomechanical deformation parameters in keratoconic (KC) and healthy eyes. METHODS: In this prospective comparative study, 29 eyes of 29 KC patients were age- and gender-matched with 28 eyes of 28 healthy individuals using frequency matching. Corneal parameters examined included the density of basal epithelial cells, anterior keratocytes, posterior keratocytes and endothelial cells as assessed by in vivo corneal confocal microscopy (HRT III-RCM, Heidelberg Engineering, www.heidelbergengineering.com). Additionally, the coefficient of variation of endothelial cell size (CV) and the percentage of hexagonal endothelial cells (HEX%) were measured by specular microscopy (Konan NSP-9900, Konan Medical, www.konanmedical.com). Further, biomechanical deformation parameters were derived from Corvis Scheimpflug Technology (Corvis ST, Oculus, www.oculus.de). All cellular and biomechanical deformation parameters in KC and normal groups were compared, and the relationship between cellular and biomechanical parameters calculated. RESULTS: In the KC group, the highest concavity (HC) delta arc length and maximum delta arc length were associated with endothelial cell density (Beta = -0.39, p = 0.03 and Beta = -0.60, p Ë‚ 0.001, respectively). Furthermore, there was a significant association between HC deflection length and HEX% (Beta = -0.67, p = 0.001). In the normal group, HC delta arc length and HC deflection length were significantly associated with endothelial cell density (Beta = 0.46, p = 0.02; and Beta = -0.51, p = 0.01, respectively). HC time, HC deformation amplitude and applanation 1 delta arc length were associated with CV (Beta = 0.50, p = 0.01; Beta = 0.27, p = 0.009; and Beta = -0.57, p = 0.002, respectively). Applanation 1 and applanation 2 deformation amplitudes were associated with HEX% (Beta = -0.49, p = 0.005; and Beta = -0.46, p = 0.02). CONCLUSIONS: Biomechanical deformation parameters were significantly correlated with endothelial cell properties in both KC and normal groups, thereby indicating the importance of the integrity of endothelial cells to the biomechanical properties of both KC and normal corneas.

Acute retinal necrosis: Clinical manifestation and long-term visual outcomes in a series of polymerase chain reaction-positive patients.

PURPOSE: To report the clinical spectrum, viral etiologies, therapeutic interventions, timing of rhegmatogenous retinal detachments (RRD), and visual outcomes in acute retinal necrosis (ARN) syndrome in a series of polymerase chain reaction (PCR)-positive eyes. METHODS: From January 2010 to January 2017, consecutive patients with the clinical diagnosis of ARN and a positive aqueous viral PCR were included in this observational, retrospective study. RESULTS: Nineteen eyes found to have a clinical diagnosis of ARN, of which 18 (94.7%) had a positive viral PCR. ARN was unilateral, except in one patient. None of the fellow eyes manifested ARN during follow-up. Varicella-zoster virus (VZV) was detected in 78.0% of ARN eyes. 61.1% of eyes experienced RRD. The median time for the occurrence of RRD was 12 weeks (range: 6-25 weeks) after disease onset. No correlation was found between the etiologic viral agent (VZV vs non-VZV; p = 1.000), extent of retinitis (1-2 quadrant vs 3-4 quadrants; p = 0.326), administration of intravitreal ganciclovir (injected vs not injected; p = 0.332), application of prophylactic laser retinopexy (applied vs not applied; p = 0.326), and subsequent occurrence of RRD.At a 2-year follow-up, visual impairment (VA ⩽ 20/200) and severe visual loss (VA ⩽ light perception) were significantly higher in those complicated by RRD compared to non-RRD eyes (81.8% vs 28.6%; p = 0.047, and 45.4% vs 0.0%; p = 0.004, respectively). CONCLUSION: Aqueous PCR results are highly consistent with the clinical diagnosis of ARN. Regardless of the method of management, the rate of RRD is high and is associated with a poor visual outcome.

Post-LASIK Ectasia Versus Keratoconus: An In Vivo Confocal Microscopy Study.

PURPOSE: To examine and compare corneal cellular and subbasal nerve (SBN) characteristics in post-laser-assisted in situ keratomileusis ectasia (PLE) corneas, normal post-laser-assisted in situ keratomileusis corneas (PLC), keratoconus (KC) corneas, and normal virgin corneas (NC). METHODS: In this cross-sectional comparative study, 18 PLE eyes of 11 patients, 18 PLC of 15 cases, 32 KC eyes of 32 patients, and 29 NC of 29 subjects were assessed using in vivo confocal microscopy. The density of the basal epithelial cell (BEC), anterior keratocyte, posterior keratocyte, and endothelial cell layers, as well as the characteristics of SBN fibers, was compared between the 4 groups. RESULTS: The density of the BEC and anterior and posterior keratocyte layers was significantly lower in KC compared with NC (-650 ± 190, P = 0.013; -181 ± 39, P < 0.001; and -36 ± 11, P = 0.021, respectively). However, there was no significant difference between PLE and PLC regarding these parameters (all Ps ≥ 0.6). Mean SBN parameters, including central corneal nerve branch density, nerve fiber length, total branch density, and nerve fiber area, were significantly lower in KC compared with NC and in PLE compared with PLC (all Ps ≤ 0.021). CONCLUSIONS: The pathophysiology of PLE seems to differ from KC. Apparent changes in the BEC and anterior and posterior keratocytes associated with KC were not observed in PLE. However, SBNs seem to be involved in both conditions.

Nanostructured lipid carriers containing rapamycin for prevention of corneal fibroblasts proliferation and haze propagation after burn injuries: In vitro and in vivo.

Chemical burns are a major cause of corneal haze and blindness. Corticosteroids are commonly used after corneal burns to attenuate the severity of the inflammation-related fibrosis. While research efforts have been aimed toward application of novel therapeutics. In the current study, a novel drug delivery system based nanostructured lipid carriers (NLCs) were designed to treat corneal alkaline burn injury. Rapamycin, a potent inhibitor of mammalian target of rapamycin pathway, was loaded in NLCs (rapa-NLCs), and the NLCs were characterized. Cell viability assay, cellular uptake of NLCs, and in vitro evaluation of the fibrotic/angiogenic genes suppression by rapa-NLCs were carried out on human isolated corneal fibroblasts. Immunohistochemistry (IHC) assays were also performed after treatment of murine model of corneal alkaline burn with rapa-NLCs. According to the results, rapamycin was efficiently loaded in NLCs. NLCs could enhance coumarin-6 fibroblast uptake by 1.5 times. Rapa-NLCs efficiently downregulated platelet-derived growth factor and transforming growth factor beta genes in vitro. Furthermore, proliferation of fibroblasts, a major cause of corneal haze after injury, reduced. IHC staining of treated cornea with alpha-smooth muscle actin and CD34 + antibodies showed efficient prevention of myofibroblasts differentiation and angiogenesis, respectively. In conclusion, ocular delivery of rapamycin using NLCs after corneal injury may be considered as a promising antifibrotic/angiogenic treatment approach to preserve patient eyesight.

Corneal chemical burn treatment through a delivery system consisting of TGF-ß1 siRNA: in vitro and in vivo.

Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFß1) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti-fibrotic TGF-ß1 siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-ß1 siRNA loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-ß1 and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts. NPs inhibited proliferation and transformation of fibroblasts to myofibroblasts by S-phase arrest and α-SMA suppression in vitro, respectively. The mentioned finding was also confirmed in vivo, addressing high wound-healing potential of prepared gene delivery system which was superior to conventional betamethasone treatment. Besides, CD4+ and α-SMA antibody staining showed inhibited angiogenesis and myofibroblast accumulation in treated corneas. This study opens a new way for treating corneal fibrosis through topical siRNA delivery.

Application of polycaprolactone nanofibers as patch graft in ophthalmology.

PURPOSE: The purpose of the study was to evaluate tissue reaction to polycaprolactone (PCL) nanofiber patches in the cornea, conjunctiva, and anterior chamber (AC) in rabbit eyes and to assess their biocompatibility for use as patch grafts. METHODS: Two 100 µ PCL patches were implanted under the conjunctiva and in the corneal stroma of one albino New Zealand rabbit, and pathologic evaluation was done after 3 weeks. In the next step, two PCL patches were implanted; one in the corneal stroma and the other in the AC of two rabbits followed by pathologic evaluation after 3 months. RESULTS: On slit-lamp examination, there was minimum inflammation in all cases. Pathologic examination showed that the contact and probably merging between the host tissue and PCL fibers were achieved with minimal tissue reaction. CONCLUSION: As a biocompatible material, PCL nanofibers seem to be a promising modality for the repair of different tissue defects including melting, thinning, and perforation. They may also be a suitable material for manufacturing keratoprostheses.

Chitosan and thiolated chitosan: Novel therapeutic approach for preventing corneal haze after chemical injuries.

Corneal haze, commonly caused by deep physical and chemical injuries, can greatly impair vision. Growth factors facilitate fibroblast proliferation and differentiation, which leads to haze intensity. In this study, the potential effect of chitosan (CS) and thiolated-chitosan (TCS) nanoparticles and solutions on inhibition of fibroblast proliferation, fibroblast to myofibroblast differentiation, neovascularization, extracellular matrix (ECM) deposition, and pro-fibrotic cytokine expression was examined. Transforming growth factor beta-1 (TGFß1) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFß1, Platelet-derived growth factor (PDGF), α-smooth muscle actins (α-SMA), collagen type I (Col I), fibronectin (Fn) and vascular endothelial growth factor (VEGF) were quantified using qRT-PCR. To assess wound-healing capacity, TCS-treated mice were examined for α-SMA positive cells, collagen deposition, inflammatory cells and neovascularization through pathological immunohistochemistry. The results revealed that CS and TCS could down-regulate the expression levels of TGFß1 and PDGF comparable to that of TGFß1 knockdown experiment. However, down-regulation of TGFß1 was not regulated through miR29b induction. Neovascularization along with α-SMA and ECM deposition were significantly diminished. According to these findings, CS and TCS can be considered as potential anti-fibrotic and anti-angiogenic therapeutics. Furthermore, TCS, thiolated derivative of CS, will increase mucoadhesion of the polymer at the corneal surface which makes the polymer efficient and non-toxic therapeutic approach for corneal injuries.

Histopathology of Conjunctivochalasis Compared to Normal Conjunctiva.

PURPOSE: To evaluate the histopathologic changes in the conjunctiva of patients with conjunctivochalasis (CCh) compared to age-matched controls. METHODS: This cross-sectional, controlled study included 27 eyes of 27 patients with CCh and 16 eyes of 16 age-matched controls. A biopsy of the bulbar conjunctiva was performed along the temporal lower lid margin before cataract surgery in both groups. Histopathologic evaluation of the specimens was done with light microscopy using staining with hematoxylin/eosin, periodic acid Schiff, and van Gieson elastic stain. Various histopathologic features of the conjunctival epithelium and stroma were compared between the two groups. RESULTS: The mean age of patients was 62.4 ± 6.9 years in the CCh group and 65.1 ± 6.3 years in the control group (P = 0.54). No significant differences were noted between the two groups in terms of conjunctival epithelial changes including papillomatosis, epithelial clefts, epithelial goblet cells, or infiltration of inflammatory cells. Mean thickness of the conjunctival stroma was 0.21 ± 0.08 mm in the CCh group and 0.26 ± 0.21 mm in the control group (P = 0.10). For the conjunctival stroma, there were no significant differences between the two groups in terms of elastosis, fibrosis, lymphangiectasia, or infiltration of inflammatory cells. CONCLUSION: No noticeable differences were found in the histopathologic features by light microscopy between eyes with CCh and those of age-matched controls. Therefore, the primary pathology of CCh may not be within the conjunctiva itself. Instead, loose attachment of the conjunctiva to the underlying tissue may be the reason for the redundant folds in the bulbar conjunctiva.

Correlations Between Histopathologic Changes and Clinical Features in Pterygia.

PURPOSE: To investigate the correlations between clinical findings and histopathologic changes in eyes with pterygium. METHODS: This prospective study included 70 eyes with primary pterygia undergoing surgical excision. Prior to surgery, clinical features of the pterygia including extension over the cornea, redness, fleshiness (based on obscuration of the underlying episcleral vessels), and obliteration of the plica semilunaris were determined. Postoperatively, pterygium specimens were examined by hematoxylin-eosin and trichrome staining to evaluate histopathologic characteristics including vascular density, leukocytic infiltration, stromal elastosis, stromal fibrosis and subepithelial fibrosis. Correlations between clinical findings and histopathologic changes were then investigated. RESULTS: There was a marginally significant correlation between the redness and the fleshiness of pterygium (P = 0.06). Both redness and fleshiness of the pterygium had significant positive correlation with dimensions of the lesion over the cornea. Moreover, larger pterygia were associated with obliteration of the plica semilunaris. Pterygium redness showed a significant correlation with vascular density (P = 0.04), and pterygium fleshiness had a significant correlation with stromal fibrosis (P = 0.04). Pterygium dimensions over the cornea demonstrated a positive correlation with vascular density and a negative correlation with stromal elastosis. CONCLUSION: Redness and fleshiness of pterygium were only marginally correlated with each other, and each one showed a correlation with different histopathologic features. Larger pterygia were associated with more significant changes at the clinical and histopathologic levels.

Albuminated PLGA nanoparticles containing bevacizumab intended for ocular neovascularization treatment.

Bevacizumab, an anti-VEGF antibody, has demonstrated trustworthy effects in treatment of retinal and choroidal neovascularization that both are crucial sight threatening conditions. However, the weak point is the short half-life of the drug in vitreous which necessitates frequent intravitreal injections. Accordingly employing controlled-release drug delivery systems such as polymeric nanoparticles (NPs) has been suggested. In this study albuminated-PLGA-NPs containing bevacizumab were prepared and studied intended for reducing the number of injections. NPs were formulated by double-emulsion method and a single dose of NPs was intravitreally injected to rabbits. The drug concentrations in vitreous and aqueous humor were assayed in different time intervals using ELISA and intraocular pharmacokinetic parameters were calculated. Moreover, coumarin-6 loaded albuminated-PLGA-NPs were employed to evaluate the distribution and persistence of the NPs in the posterior segment. Results revealed that the bevacizumab vitreous concentration maintained above 500 ng mL(-1) for about 8 weeks and 3.3 times elevation was observed in the drug vitreous MRT compared with the control. According to coumarin-6 NP tests, fluorescence emissions in posterior tissues were observed for 56 days which confirmed the nanoparticles persistence in ocular tissues during the test span. Therefore our prepared formulation may offer improvements in treatment of eye posterior segment neovascularization.

Triamcinolone acetonide as an adjunct to bevacizumab for prevention of corneal neovascularization in a rat model.

PURPOSE: To evaluate the short-term effects of a single subconjunctival injection of triamcinolone acetonide as an adjunct to subconjunctival bevacizumab for prevention of corneal neovascularization in rats. METHODS: Chemical cauterization was performed in the central cornea of the right eye in 48 male Sprague-Dawley rats (4 eyes were excluded due to perforation and/or infection). Immediately after the injury, the rats were randomly assigned to four treatment groups: controls (n=10), received subconjunctival injection of 0.02 mL balanced salt solution; group 1 (n=12), received 0.02 mL bevacizumab (25 mg/mL); group 2 (n=11), were treated with 0.02 mL triamcinolone acetonide (40 mg/mL); and group 3 (n=11), received both bevacizumab and triamcinolone acetonide. On days 7 and 14 after cauterization, digital photographs of the corneas were taken and the area of neovascularization was calculated and compared among the study groups. RESULTS: The area of corneal neovascularization in all three treatment groups was less than the controls (P<0.05 for all comparisons). On day 7, the corneal avascular area was largest in group 3 (63%). On day 14, the area of corneal neovascularization in groups 2 and 3 was smaller than that in group 1 (P=0.031 and 0.011, respectively), but the difference between groups 2 and 3 was not statistically significant (P=0.552). Microscopic evaluation of the cornea was compatible with gross findings; inflammation and the number of new vessels was the least in group 3. CONCLUSION: Triamcinolone acetonide was more effective than bevacizumab in inhibiting corneal neovascularization. Its adjunctive administration to bevacizumab resulted in even better prevention of corneal neovascularization. However, the produced combined effect was less than the sum of their separate effects and did not match additive or synergistic interactions.

Healing efficacy of an EGF impregnated triple gel based wound dressing: in vitro and in vivo studies.

To accomplish an ideal wound healing process which promotes healthy tissue growth with less scaring, a novel gel based topical drug delivery system composed of 3 different polymers chitosan, dextran sulfate, and polyvinylpyrrolidone K30 (CDP) was prepared. The physicochemical properties of the prepared gels were investigated in vitro. Gels showed a maximum swelling ratio of 50 ± 1.95 times of dried gel in PBS at pH 7.4. The swelling ratios increase in acidic and alkaline pH to 55.3 ± 1.75 and 65.5 ± 2.42, respectively. In the rheological test, prepared gels revealed viscoelastic properties and a small linear viscoelastic region of 0.166%. In vivo wound healing promoting activities of CDP gels containing 20 µg/mL EGF were evaluated on surgically induced dermal wounds in rats using pathologic examination. The application of CDP gel with incorporated EGF significantly reduced the defect on the rat's skin and enhanced epithelial healing compared with the topical application of the EGF-free CDP gel. The results clearly substantiate the beneficial effects of the topical application of CDP containing EGF in the acceleration of healthy wound healing process with less scarring.

Amniotic Membrane Extract Preparation: What is the Best Method?

PURPOSE: To compare different preparation methods for a suitable amniotic membrane (AM) extract containing a given amount of growth factors. METHODS: In this interventional case series, we dissected the AM from eight placentas within 24 hours after delivery, under clean conditions. After washing and mixing, AM extracts (AMEs) were prepared using pulverization and homogenization methods, and different processing and storing conditions. Main outcome measures were the amount of added protease inhibitor (PI), the relative centrifugal force (g), in-process temperature, repeated extraction times, drying percentage, repeated pulverization times, and the effect of filtering with 0.2 µm filters. Extract samples were preserved at different temperature and time parameters, and analyzed for hepatic growth factor (HGF) and total protein using ELISA and calorimetric methods, respectively. RESULTS: The extracted HGF was 20% higher with pulverization as compared to homogenization, and increased by increasing the PI to 5.0 µl/g of dried AM. Repeating centrifugation up to 3 times almost doubled the extracted HGF and protein. Storing the AME at -170° for 6 months caused a 50% drop in the level of HGF and protein. Other studied parameters showed no significant effect on the extracted amount of HGF or total protein. CONCLUSION: Appropriate extraction methods with an adequate amount of PI increases the level of extractable components from harvested AMs. To achieve the maximal therapeutic effects of AMEs, it is necessary to consider the half-life of its bioactive components.

Analysis of superoxide dismutase 1, dual-specificity phosphatase 1, and transforming growth factor, beta 1 genes expression in keratoconic and non-keratoconic corneas.

PURPOSE: To quantitatively assess the superoxide dismutase 1 (SOD1), transforming growth factor, beta 1 (TGF-ß1), and dual-specificity phosphatase 1 (DUSP1) messenger ribonucleic acid (mRNA) expression levels as the main intracellular reactive oxygen species neutralizers, wound healing mediators, and immunomodulators (respectively) in keratoconic (KCN) and non-KCN corneas. METHODS: Total RNA was extracted from normal and keratoconic cultured corneal stromal fibroblasts. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to measure the relative expression levels of mRNAs of the SOD1, TGF-ß1, and DUSP1 genes. RESULTS: The mRNA expression of TGF-ß1 and DUSP1 was augmented in the KCN corneas (three- and fivefold, respectively; both p<0.05). The KCN and non-KCN samples showed no difference in comparative SOD1 mRNA levels. CONCLUSIONS: This study demonstrated a higher level of DUSP1 and TGF-ß1 expression as known molecules in the inflammatory process. These results may provide new insight into the complex molecular pathways underlying KCN for investigating other inflammatory molecules.

Biochemical and pathological evidences on the benefit of a new biodegradable nanoparticles of probiotic extract in murine colitis.

Efficacy of probiotics in the management of human inflammatory bowel disease (IBD) has been approved in the recent years. In the present work, the efficacy of a new biodegradable nanoparticles (NPs) of encapsulated and lyophilized probiotic extract (LPE) was examined in murine colitis. Colitis was induced by rectal instillation of trinitrobenzen sulfonic acid to male Wistar rats. The safety and effective dose of LPE was determined in a pilot study. To ease delivery into colon, LPE was encapsulated in chitosan-coated-poly (lactide co glycolide acid) NPs. After induction of colitis, animals in different groups received test compound in three doses by gavage for 10 days. Groups of sham, control (saline), and standard (dexamethasone) were also assigned. Colonic pathological examination, tumor necrosis factor alpha, interlukin (IL)-1ß, myeloperoxidase (MPO), and lipid peroxidation (LPO) were performed. LPE at all doses (273, 545, and 1100 mg/kg) had positive effects in reduction of pro-inflammatory cytokines, LPO, and MPO in a dose-dependent manner. The formulated compound containing medium dose of LPE was more efficient in mitigating the experimental colitis in comparison with that of high-dose LPE. It is concluded that LPE and its nanoparticle-encapsulated form are very much effective in control of colitis. Regarding safety of this compound, further studies can be conducted in patients with IBD.

Repeated applications of impression cytology to increase sensitivity for diagnosis of conjunctival intraepithelial neoplasia.

PURPOSE: To increase sensitivity of impression cytology (IC) for the diagnosis of conjunctival intraepithelial neoplasia (CIN) by three repeated applications of IC. METHODS: This study included 35 eyes with a clinical diagnosis of CIN and 6 eyes with pinguecula as control. All eyes received IC by three consecutive applications of the cellulose acetate filter paper. All eyes in the CIN group had subsequent surgical excision with histopathological evaluation. The sensitivity of each application of IC for the diagnosis of CIN was determined. RESULTS: In the control group, all IC specimens were negative for CIN. In the CIN group, with positive histopathology in all cases, the first IC was positive in 17 eyes (56.7%), showed atypical squamous cells indefinite for dysplasia (ASCID) in 8 (26.7%) and was negative in 5 (16.6%). The second application was positive in 25 eyes (83.3%), showed ASCID in 3 (10%) and was negative in 2 (6.7%). The third application was positive in 26 eyes (87.7%), showed ASCID in 3 (10%) and was negative in 1 (3.3%). The second application resulted in a statistically significant higher positive yield than the first application (p=0.009), with no significant difference between the second and the third applications (p=0.12). CONCLUSION: Consecutive repeated applications of filter paper significantly increased the diagnostic sensitivity of IC for the diagnosis of CIN.

Pretreatment with oxygen protects rat kidney from cisplatin nephrotoxicity.

Cisplatin (CP) nephrotoxicity is mainly due to reactive oxygen species. Oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on cisplatin-induced acute renal failure was investigated in present study. Twenty-four rats were divided into four groups. The O(2)+ CP and Air + CP groups were were subjected to i.p. injection of 5 mg/kg cisplatin, and in the Air + Saline and O(2) + Saline groups, saline was injected instead of cisplatin. O(2)+ CP and O(2)+ Saline groups were pretreated with oxygen (3h/d for two days), and the other two groups were pretreated with room air. Cisplatin was administered 24 h after last pretreatment session. Three days after cisplatin injection, plasma samples were obtained, and parts of kidney tissue were frozen for biochemical analysis or fixed in formalin for histological assessments. Preconditioning with oxygen prior to cisplatin administration led to reduced tubular necrosis and luminal cast formation and improvement of renal function, as was evidenced by significant reduction in plasma creatinine and urea levels. Oxygen pretreatment also significantly reversed cisplatin-induced reduction in renal catalase activity and glutathione level. It could be concluded that oxygen pretreatment could have a delayed protective effect against cisplatin nephrotoxicity, and that increased renal catalase activity may be involved in this protective effect of hyperoxia.