Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence from an Animal Model.

BACKGROUND: Taxifolin (TXF) is a flavonoid found abundantly in citrus/onion. Encouraging results on its renoprotective effect have been reported in a limited number of drug-induced nephrotoxicity animal models. The present study aimed to evaluate for the first time the potential renoprotective effects of TXF in a paracetamol (PAR)-induced nephrotoxicity rat model. METHODS: Rats were divided into three equal groups (n = 6 animals per group). Group 1 (PAR group, PARG) received PAR diluted in normal saline by gavage (1000 mg/kg). Group 2 (TXF group, TXFG) received TXF diluted in normal saline by gavage (50 mg/kg) one hour after PAR administration. Group 3 (control group, CG) received normal saline. Twenty-four hours after PAR administration, all animals were sacrificed using high-dose anesthesia. Blood samples were collected and kidneys were removed. RESULTS: The serum blood urea nitrogen, creatinine levels and serum malondialdehyde levels were significantly increased in the PARG. The serum glutathione peroxidase, glutathione reductase and total glutathione levels were significantly higher in the TXFG. At the same time, the kidneys of the PARG animals demonstrated tubular epithelium swelling, distension and severe vacuolar degeneration. The kidneys of the TXFG animals showed mildly dilated/congested blood vessels. CONCLUSIONS: The TXF renoprotective effects are promising in preventing PAR-induced nephrotoxicity, mainly through antioxidant activity, and warrant further testing in future studies.

Effect of lutein on methotrexate-induced oxidative lung damage in rats: a biochemical and histopathological assessment.

BACKGROUND/AIMS: This study aimed to investigate the effect of lutein on methotrexate (MTX)-induced pulmonary toxicity in rats biochemically and histopathologically. METHODS: The rats in the MTX + lutein (MTXL, n = 6) group were given 1 mg/kg of lutein orally. A 0.9% NaCl solution was administered orally to the MTX (n = 6) group and the healthy group (HG, n = 6). One hour later, a single 20 mg/kg dose of MTX was injected intraperitoneally in the MTXL and MTX. Lutein or 0.9% NaCl solution was administered once a day for 5 days. At the end of this period, malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) were measured in the lung tissues from the animals euthanized with 50 mg/kg thiopental sodium anesthesia. Subsequently, histopathological examinations were performed. RESULTS: The levels of MDA, MPO, IL-1ß, and TNF-α in the lung tissue of the MTX were significantly higher than those of the MTXL and HG groups (p < 0.0001), and the amount of tGSH was lower. The histopathological findings in the MTX group, in which the oxidants and cytokines were higher, were more severe. CONCLUSION: Lutein prevented the MTX-induced oxidative lung damage biochemically and histopathologically. This result indicates that lutein may be useful in the treatment of MTX-induced lung damage.

The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats.

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1ß, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1ß and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Effect of Hippophae rhamnoides Extract on Oxidative Oropharyngeal Mucosal Damage Induced in Rats Using Methotrexate.

OBJECTIVES: The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. METHODS: Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. RESULTS: The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1ß, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. CONCLUSION: HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.

Should orthopedic surgeons consider the effects of gabapentin administration on bone healing while treating a long bone fracture: experimental study in a rat model.

OBJECTIVE: The main purpose of the present study was to assess the radiographic, histological, and mechanical effects of gabapentin on fracture healing in a rat model of femur fracture. MATERIALS AND METHODS: A standard transverse fracture of the mid-diaphysis was created. A total of 60 female Wistar-Albino rats with the mean age of 13.5 ± 1.2 weeks were used for this experimental trial. The rats were randomized into four groups with 15 animals included in each group. Group A and B were the control groups whereas C and D were the treatment groups. Drugs were delivered by oral gavage twice a day with the daily dosage calculated according to body surface area conversion to the human equivalent dosing regimen of 1200 mg/day. Radiographic, histological, and biomechanical evaluation was performed. RESULTS: We could not detect any statistically significant difference between the control and gabapentin treatment groups according to the comparative assessment of radiographic scores on the 15th and 30th days. Although no significant differences were found between the groups on the 15th day, histological scores were better in the control group on the 30th day. According to the results of biomechanical testing, the fractured femurs resected from the control group exhibited significantly more strength on the 30th day. CONCLUSIONS: According to the data we acquired during the present study, administration of gabapentin negatively affects the fracture healing process especially in the aspects of histological progression as well as the biomechanical strength of the callus in a rat model.

Effect of Kineret® on ovarian ischemia reperfusion injury in a rat model.

AIM: To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries. METHODS: Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR-50); 100 mg/kg Kineret® + ovarian IR (KIR-100); and sham operation (SOC). KIR-50 (n = 10) and KIR-100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups. RESULTS: In rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL-1ß) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret® at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL-1ß and a decrease in tGSH caused by IR more significantly than administration of Kineret® at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret® significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret® at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret. CONCLUSION: Our findings indicate that Kineret® might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion.

The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.

OBJECTIVE: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue. MATERIALS AND METHODS: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA. RESULTS: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 µmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1ß (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1ß, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group. CONCLUSION: In this study, ileal damage caused by MTX was inhibited by RST.

The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue.

INTRODUCTION: Beta-carotene is a well-known antioxidant and precursor of Vitamin A that has a preventative role in the oxidative damage process. Our aim was to investigate the possible preventive effects of beta-carotene on oxidative damage via experimental ischemia and ischemia-reperfusion models in rat ovaries. MATERIALS AND METHODS: A traumatic vascular clamps were used for 3h to induce ischemia (Group 2, 3, 4, 5, 6, 7). The clamps were then removed to allow reperfusion for 3h (Group 3, 6, 7). Sham-operated rats (Group 1) underwent laparotomy without the induction of ischemia/reperfusion injury. Real-Time-PCR was performed to determine IL-1-beta, IL-6 and iNOS expression levels. Histopathological (H&E) and immunohistochemical staining (NF-kß p65) processes were then performed. Finally, SOD, GSH, and MDA levels were determined. RESULTS: Intense hemorrhagic areas were observed in both the ischemia and ischemia/reperfusion groups, whereas minimal hemorrhage was observed in the treatment groups. The ischemia and ischemia/reperfusion groups exhibited extreme immunoreactivity, detected by NF-kß p65 staining; this reactivity decreased after the application of beta-carotene. The expression of IL-1-beta, IL-6, and iNOS in the injury groups increased significantly, whereas a dose-dependent improvement was observed in the treatment groups. Finally, MDA levels increased significantly and SOD and GSH levels decreased drastically in the injury groups. However, these values obtained from I/R groups were normalized after beta-carotene treatment. DISCUSSION: In this study, we demonstrated via molecular and biochemical parameters the protective effect of beta-carotene, which is a potent antioxidant, on the experimental ischemia-reperfusion model.

Anatomy of the Anterior Deep Temporal Nerve: Implications for Neurotization in Blinking Restoration in Facial Paralysis.

Facial paralysis can lead to dysfunctions in eyelid closure, which is called lagophthalmos. A number of surgical procedures, both dynamic and static, have been described to restore the innervation of the orbicularis oculi muscle that closes the eyelids. This cadaver-based anatomical study aimed to evaluate the anatomy of the anterior, middle, and posterior deep temporal nerves; nerves to the temporalis muscle; and their availability for direct muscle neurotization of the orbicularis oculi. A total of 10 hemisectioned head specimens from 5 adult cadavers (2 men and 3 women) were used in this study. The adequacy of the length of the anterior deep temporal nerve was assessed for direct neorotization of the orbicularis oculi muscle. The mean distances between the originating point of the deep temporal nerves from the mandibular nerve in the infratemporal fossa and their terminal entry points into the muscle were 46.4 (42-51 mm), 42.2 (38-46 mm), and 33.4 mm (26-40 mm) for the anterior, middle and posterior branches of the nerves, respectively. We conclude that the anterior deep temporal nerve is a versatile nerve that can be used for direct muscle neurotization, nerve transfer, and babysitter procedures in selective blinking restoration. Before proceeding with any further clinical use, an anatomical study should be performed with fresh specimens from cadavers.

Are new generations getting bigger in size? Anthropometric measurements in erzurum.

OBJECTIVE: When the dimensional measurements of the students who spend most of their time at school are taken into consideration, inappropriate dimensions of school equipment may affect their body and psychological improvements negatively. Anthropometric measurements are necessary for designing the educational equipment of the children at school. It is emphasized that anthropometric measurements of the people living in different climate and altitude conditions will be different. It is mentioned that anthropometric data available for a certain region will be able to change as a result of changing socio-economical conditions and therefore, anthropometric data update is necessary at certain periods. MATERIALS AND METHODS: In 2000 anthropometric data obtained from the children between the age of seven and fifteen, who were in sitting and standing positions, were measured with a repeated measurement in the same schools in 2007. RESULTS: Mean values of the heights of elbow at standing position of the female students, 8 years old, increased from 72.38 cm in 2000 to 74.67 cm in 2007 (p<0.001). Most of the other measurements in 2007 were larger than those in 2000, giving the impression that new generation children are getting larger in size. CONCLUSION: As reported in the literature, anthropometric data should be updated at certain period of times.

Height, weight and body mass index percentiles of children aged 6-14 years living at moderate altitudes.

OBJECTIVE: Individuals living at high altitudes are reported to have lower stature and also a smaller chest size in relation to their stature. Altitude-related hypobaric hypoxia is considered to be the major cause of these alterations in growth, but adverse socioeconomic and/or other environmental conditions may also have a role in poor growth performance. This study was undertaken to provide growth data on children and adolescents living in a moderate-altitude area in Turkey. METHODS: The dataset of an anthropometric study conducted among a population living in a city at an altitude of 2000 meters was analyzed. A total of 1638 children and adolescents (871 males and 767 females) aged between 6 and 14 years were included in this study. The LMS method was used in the analysis and percentile values corresponding to the 3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th and 97th percentiles for height, weight and body mass index (BMI) were estimated. The results were compared with the measurements of children and adolescents living in areas of lower altitude in Turkey. RESULTS: Starting at ages 0-10 years, height, weight and BMI values of children and adolescents of both genders living at an altitude of 2000 meters were noticeably lower than those reported for their counterparts living in areas of lower altitude in Turkey. CONCLUSIONS: The higher values for height, weight and BMI in children living in low-altitude areas can be attributed to altitude effect, but socioeconomic and microclimate effects cannot be discarded and further studies are needed.

The effects of testosterone on intestinal ischemia/reperfusion in rats.

ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.

Number of axons in the right and left optic nerves of right-pawed and left-pawed rats: a stereologic study.

OBJECTIVE: To compare the number of axons in the right and left optic nerves of right- and left-pawed rats. STUDY DESIGN: In this study, optic nerve samples were obtained from right- and left-pawed rats and axon numbers of optic nerves and vice versa were stereologically and histologically evaluated. RESULTS: In the right-pawed rats, more axons were found in the right optic nerve than in the left optic nerve, and left-pawed rats had more axons in the left optic nerve than in the right optic nerve. CONCLUSION: The paw preference is associated with eye dominance and the number of axons in the ipsilateral optic nerve.

A stereological and electron microscopic study of the development of the nephron in prenatal and postnatal rats.

OBJECTIVE: To describe the morphometric and ultra-structural features of the kidney in fetal (20-day-old), newborn (7-day-old) and adult (180-day-old) rats. MATERIALS AND METHODS: Kidneys from all animals were excised, fixed in 3% glutaraldehyde in 0.1 M phosphate buffer, post-fixed in 1% phosphate-buffered osmium tetroxide, and examined by stereological and light and electron microscopic methods. RESULTS: Fetal kidneys displayed kidney corpuscles, glomeruli, and proximal and collective tubules at multiple developmental stages. Glomeruli in the outer surfaces of the kidney were less mature than those in the inner surface. Kidney corpuscles were made up of parietal cells and podocytes without feet. Kidneys from newborn rats were almost completely developed, while kidneys in adult rats were fully developed. Under stereological examination, the percent volume of cortex in fetal kidneys (86.19%) was higher than in newborn (53.77%) or adult rats (76.78%). Compared to both newborn and fetal rats, adult rats displayed the highest total volumes of distal and proximal tubules, but lower mean glomerular or Bowman's capsule volumes. On the other hand, the total number of glomeruli was increased in adult rats (32,600) as compared to newborn (17,896) and fetal (11,650) rats. CONCLUSION: These data suggest that development of metanephric kidneys is not yet complete by gestational day 20, but is almost complete at postnatal week one. Furthermore, the developmental stage of the kidney, as determined by stereology, correlates well with the age of the rat.

The effects of extracorporeal shock wave lithotripsy on antioxidant enzymes in erythrocytes.

The effects of extracorporeal shock wave lithotripsy (ESWL) on patients undergoing ESWL for renal stone treatment have been studied using activities of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and catalase (CAT), and levels of malondialdehyde (MDA) in the erythrocyte haemolysate. The study included 23 patients (eight women, 15 men with an age range of 23-57 years). Blood samples were taken 5 min before ESWL, in addition to 1 h and 5 days after termination of treatment. Enzyme activities and MDA levels in erythrocytes were measured spectrophotometrically. When compared with the values obtained before ESWL, erythrocyte G6PDH (p = 0.015), SOD (p = 0.036) and CAT (p = 0.01) activities were found to be significantly reduced at the first hour after ESWL. On the fifth day after ESWL, erythrocyte enzyme activities were normalized to the values obtained before ESWL. Although there was a significant difference between values before and 1 h after ESWL (p = 0.003), no difference was detected between 1 h after ESWL and 5 days after ESWL (p > 0.05) in terms of MDA values. The findings of the present study revealed that erythrocyte lipid peroxidation might be induced and antioxidative defence mechanism may be transiently impaired by ESWL.