Protective effect of pregabalin on renal and renal endothelial damage in sepsis induced by lipopolysaccharide.

OBJECTIVE: We investigated the protective effects of pregabalin (PRG) on kidney and renal endothelial damage in sepsis induced by Lipopolysaccharide (LPS). MATERIALS AND METHODS: Rats were randomly divided into three groups as control, LPS and LPS+PRG. Saline solution was administered 30 mg/kg orally and 5 mg/kg intraperitoneally (i.p.) to the control group. LPS was applied as 5 mg/kg, i.p. to the LPS group. In the LPS+PRG group, PRG at 30 mg/kg orally and one hour before LPS administration, one hour later 5 mg/kg i.p. LPS was applied. Rats were sacrificed 6 hours after LPS administration. RESULTS: White Blood Cell (WBC), granulocyte, Blood Urea Nitrogen (BUN), creatinine, uric asid, Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) significantly increased (p<0.05); platelets (PLT), activated partial thromboplastin time (aPTT) and Total Antioxidant Status (TAS) significantly decreased in the LPS group compared to the control group (p<0.05). In the LPS+PRG group WBC, granulocyte, BUN, creatinine, uric asid, TOS and OSI significantly decreased (p<0.05); PLT, aPTT and TAS significantly increased compared to the LPS group(p<0.05). Histopathological examinations showed that kidney and renal endothelial damage in the LPS group decreased in the LPS+PRG group. Immunohistochemically IL1-ß, IL-6, IL-10, TNF-α expressions in kidney tissue and Toll-Like Receptors-4 (TLR-4) and NF-κB expressions in the renal endothelial tissue significantly increased in the LPS group compared to the control group and significantly decreased in the LPS+PRG group compared to the LPS group (p<0.001). CONCLUSIONS: Sepsis causes kidney and renal endothelial damage and PRG reduces this damage. Therefore PRG can be used in prophylactic treatment in sepsis, supported by more studies.

In this study, kidney and renal endothelial damage in sepsis was investigated. The effect of pregabalin on kidney and renal endothelial damage in sepsis was evaluated.

Agomelatine ameliorates doxorubicin-induced cortical and hippocampal brain injury via inhibition of TNF-alpha/NF-kB pathway.

Side effects of doxorubicin (DOX) are mainly due to oxidative stress, with the involvement of inflammatory and apoptotic mechanisms. Agomelatine (AGO) is a melatonin receptor agonist with antioxidant, anti-inflammatory, and anti-apoptotic features. This study aimed to evaluate the effects of AGO with different doses on DOX-induced neurotoxicity. Rats were divided into four groups as control, DOX (40 mg/kg, intraperitoneal single dose), DOX + AGO20 (20 mg/kg AGO oral gavage for 14 days), and DOX + AGO40 (40 mg/kg AGO oral gavage for 14 days). On day 14, brain tissues were collected for biochemical, histopathological, and genetic examinations. DOX significantly increased malondialdehyde and decreased superoxide dismutase and catalase (CAT) levels. CAT levels were significantly increased only in the DOX + AGO40 group compared to the DOX group (p = 0.040) while other changes in oxidant and antioxidant indicators were insignificant. DOX-induced significant increases in TNF-alpha and NF-κB were reversed following both low and high-dose AGO administration in a dose-dependent manner (p < 0.001 for both doses). Cellular shrinkage, pycnotic change, and vacuolization in apoptotic bodies were apparent in the cortical and hippocampal areas of DOX-treated samples. Both doses of AGO alleviated these histopathological changes (p = 0.01 for AGO20 and p = 0.05 for AGO40). Significantly increased apoptosis shown with caspase-3 immunostaining in the DOX group was alleviated following AGO administration, with additional improvement after high-dose treatment (p < 0.01 for DOX compared to both AGO groups and p < 0.05 for AGO40 compared to AGO20). AGO can be protective against DOX-induced neurotoxicity by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in a dose-dependent manner.

Protective effects of resveratrol and avocado oil against paracetamol-induced hepatotoxicity in rats.

This study sought to assess the protective effects of resveratrol and avocado oil in relation to paracetamol-induced hepatotoxicity in rats. The rats were divided into five groups, namely the control, paracetamol (600 mg/kg), resveratrol (RES; 10 mg/kg) + paracetamol, avocado oil (AVO; 200 mg/kg) + paracetamol, and RES + AVO + paracetamol groups. The hepatoprotective activity was evaluated by measuring biochemical parameters such as the total antioxidant status (TAS) and the total oxidant status (TOS) in each rat's liver homogenates. Any DNA damage was assessed by means of a comet assay. The results showed that the TOS levels were significantly increased in the paracetamol group when compared with the control group. The TOS levels were found to be significantly lower in the paracetamol groups, in comparison with the RES, AVO, and RES + AVO groups. Moreover, the TAS levels significantly increased in the RES and RES + AVO groups when compared with the paracetamol group. The histopathological examination revealed necrotic areas in the rats' livers. Pretreatment with both RES and RES + AVO was found to reverse the oxidative stress parameters, DNA damage, and necrosis induced by paracetamol. These results suggest that a combination of REV and AVO may protect against paracetamol-induced hepatotoxicity due to their antioxidant properties.

Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats.

The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty-four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20 mg/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20 mg/kg MTX, i.p, single dose+40 mg/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24 hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony-stimulating factor (G-CSF), osteopontin (OPN), and heat shock protein-70 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G-CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.

The effects of high-fructose corn syrup consumption on testis physiopathology-The ameliorative role of melatonin.

This study investigated the ameliorative role of melatonin (MLT) and the effects of a long-term intake of high-fructose corn syrup (HFCS) on the male reproductive system. Thirty-six male Sprague Dawley rats were randomly divided into 3 groups as follows: Control, HFCS and HFCS + MLT. Testis and epididymal weights were measured. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, total testosterone levels, testicular histopathological damage scores were evaluated, and immunohistochemical analyses were performed on testicular tissue. Epididymal weights were significantly lower in the HFCS + MLT group than those of the control and HFCS groups. MDA was significantly increased, while SOD and CAT activities were reduced in the HFCS group compared with the control group. Administration of melatonin significantly increased SOD and CAT activities in the HFCS + MLT group. Histopathological evaluation revealed slight hyperaemia and oedema in the stromal tissue of rat testes in the HFCS group. Sperm count and Johnsen's testicular biopsy score (JTBS) were significantly decreased in the HFCS group. Immunohistochemical analysis revealed that HSP, iNOS, MDA, OPN and VEGF values were significantly increased in the HFCS group. However, melatonin ameliorated the immunohistochemical scoring. Our results showed that a long-term intake of HFCS caused testicular damage. Melatonin may be a promising pharmacological agent against testicular toxicity induced by HFCS.

The impact of electromagnetic radiation (2.45 GHz, Wi-Fi) on the female reproductive system: The role of vitamin C.

The present study investigated the effects of applied continuous 2.45 GHz electromagnetic radiation (EMR), which might cause physiopathological or morphological changes in the ovarian, fallopian tubal, and uterine tissues of rats. We proposed that the addition of vitamin C (Vit C) may reduce these severe effects. Eighteen female Sprague Dawley rats were randomly divided into three groups with six animals in each: Sham, EMR (EMR, 1 h/day for 30 days), and EMR + Vit C (EMR, 1 h/day for 30 days 250 mg/kg/daily). Total oxidant status (TOS) and oxidative stress index (OSI) levels increased ( p = 0.011 and p = 0.002, respectively) in the EMR-only group in ovarian tissues. In all tissues, TOS and OSI levels significantly decreased in the Vit C-treated group in ovarian, fallopian tubal, and uterine tissues ( p < 0.05). Anti-müllerian hormone levels significantly increased in the EMR group ( p < 0.05) and decreased in the Vit C-treated groups. Estrogen (E2) levels were unchanged in the EMR group, as the differences were not statistically significant. Immunohistochemical examination of the ovaries revealed significant increases in Caspase-3 expressions in the epithelial cells of the EMR group ( p < 0.05). In the EMR group, hyperemia was observed in uterine tissues. Also, Caspase-3 and Caspase-8 were significantly increased in the EMR group ( p < 0.001). Caspase-3 was significantly diminished with Vit C application in the ovarian and uterine tissues ( p < 0.05). Caspase-8 was significantly diminished only in uterine tissues ( p < 0.05). These results indicate that prolonged EMR exposure induced physiopathological changes in the ovarian, fallopian tubal, and uterine tissues due to oxidative damage. Under the conditions of this study, Vit C may have protective effects on female reproductive system against oxidative damage.

Whey protein supplementation reduced the liver damage scores of rats fed with a high fat-high fructose diet.

Different functional foods with bioactive nutrients are being explored for the management of NAFLD. Whey proteins are rich in bioactive peptides and are suggested to show antioxidant and anti-inflammatory effects. We aim to test the hypothesis that the whey protein supplementation following a high fat-high fructose (HFHF) diet would protect against liver damage, inflammation, endotoxemia and steatosis in male Wistar rats. 36 rats were randomized into four groups for 8 weeks as the HFHF diet group, HFHF diet and whey protein isolate (WPI-200mg/kg/day) group (HFHF+WPI), control (C) group, and C+WPI (200mg/kg/day) group. Rats fed with a HFHF diet had higher final body weight compared to C and C+WPI groups (p = 0.002). Thus, WPI showed no significant effects for the body weight of rats with a HFHF diet. On the other hand, the HFHF+WPI group had significantly lower abdominal circumference when compared with the HFHF group (p<0,001). Higher serum CRP levels were observed in the groups with a HFHF diet (p<0,001) and WPI supplementation showed no effects on CRP levels. Whey protein supplementation resulted with lower total liver damage score in HFHF+WPI group compared with the HFHF diet group (p<0,001). Conversely, higher liver damage scores were observed with the C+WPI group compared to C group (p<0,001). HFHF diet resulted with higher expression of TLR-4 in the liver meanwhile WPI supplementation showed no effects on liver TLR-4 expression. We observed higher colon Occludin expression in HFHF+WPI and C+WPI groups compared with HFHF and C groups (p<0,001). Our results showed that, whey protein supplementation might help improve liver damage associated with a high fat-high fructose diet and increase the expression of Occludin in the small intestine and colon.

Protective effect of vitamin D on learning and memory impairment in rats induced by high fructose corn syrup.

In our study, we aimed to investigate the negative effects of the prefrontal cortex (PFC)-associated impairment of cholinergic activity on memory and learning caused by high fructose corn syrup (HFCS) and the protective role of vitamin D in adolescent rats. Twenty-four animals were divided into three groups as control, HFCS group (11 % HFCS-55 solution, ad libitum) and HFCS+ Vit D (42 µg/kg/day). Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM, performed from day 23) tests were applied to all animals. Fluid intake consumption of the rats was measured daily, weight gain and blood glucose were measured weekly. After 31 days of treatment, the rats were sacrificed and PFC tissue was removed for biochemical, histopathological and immunohistochemical analyses. In HFCS group, fluid consumption, blood glucose, malondialdehyde (MDA) levels, degenerative neuron count and choline acetyltransferase (ChAT) expression were significantly increased; superoxide dismutase (SOD), catalase (CAT) enzyme activity and brain-derived neurotrophic factor (BDNF) expression were significantly decreased. In addition, the time spent in the enclosed arm in EPM was increased, the immobility time in FST was, and the time spent in the target quadrant in MWM was significantly decreased. Vitamin D treatment reversed all these parameters. In conclusion, HFCS caused an increase in the number of degenerative neurons in the PFC, disrupted cholinergic activity and negatively affected learning-memory functions. Vitamin D, decreased the number of degenerative neurons, increased cholinergic activity and positively affected learning and memory performance. BRIEF SYNOPSIS: In this study, prefrontal cortex damage was investigated in adolescent rats fed high fructose corn syrup. The effect of vitamin D on prefrontal cortex damage was evaluated.

Effects of sage (Salvia officinalis) essential oil on growth, health and antioxidant capacity of common carp (Cyprinus carpio).

In the study, effects of S. officinalis essential oil on growth performance, health and antioxidant activity in C. carpio were investigated. The fish (13 ± 0.21 g) were fed with diet containing 1 and 3 ml kg- 1 of sage oil for 60 days. At the end of study, growth performance was not affected in fish fed with sage essential oil (p > 0.05). Superoxide dismutase (SOD) activity in hepatopancreas increased with addition of 1ml kg- 1 sage oil to the diet. However, Catalase (CAT) activity and malondialdehyde (MDA) values were not significantly altered in common carp. Total protein, albumin, glucose and hepatopancreas enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)) in blood serum were not affected by sage essential oil supplementation. At the histological examinations, no pathological findings were observed in hepatopancreas and intestine of carp. Goblet cells number and villi length in intestine increased with sage supplementation (p < 0.001). In addition, fertility, granulation and number of follicles increased in common carp fed with sage essential oil. Mortality after challenged with A. hydrophila was not observed in carp fed with 1ml kg- 1 concentration of sage essential oil. As a result, use of sage oil can be recommended in carp farming to improve gut health, provide disease resistance against A. hydrophila infection, and increase of fertility.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

INTRODUCTION: Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. MATERIAL AND METHODS: The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. RESULTS: Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. CONCLUSIONS: Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

Astaxanthin ameliorates damage to the cerebral cortex, hippocampus and cerebellar cortex caused by methotrexate.

We investigated the ameliorating effects of astaxanthin (AXA) on methotrexate (MTX) induced damage to the cerebral cortex, hippocampus, cerebellar cortex and blood. We used 24 female Wistar albino rats divided into three groups of eight as follows: sham/control group, single dose of saline intraperitoneally (i.p.) and 7 days orally; MTX group, single dose of 20 mg/kg MTX (i.p.); MTX + AXA group, single dose of 20 mg/kg MTX i.p.+ 100 mg/kg AXA orally for 7 days. For all groups we measured total oxidant status (TOS) and total antioxidant status (TAS) in the cerebral cortex, hippocampus and blood. Histological sections of cerebral cortex, hippocampus and cerebellar cortex were inspected microscopically. Caspase-3 (cas-3), granulocyte colony-stimulating factor (GCSF), growth related oncogene (GRO), inducible nitric oxide synthase (iNOS) and myelin basic protein (MBP) were estimated immunohistochemically in the cerebral cortex, hippocampus and cerebellar cortex. In the MTX group, TAS was decreased significantly in the cerebral cortex, hippocampus and blood, while TOS was significantly increased. AXA significantly ameliorated oxidative stress parameters in the cerebral cortex and hippocampus. Histopathological examination revealed degeneration, edema and hyperemia in the cerebral cortex, hippocampus and cerebellar cortex in the MTX group. AXA treatment ameliorated histopathological changes. MTX decreased MBP expression in cerebral cortex. Although MBP expression was decreased in the cerebral cortex, hippocampus and cerebellar cortex stimulated with MTX, the expressions of cas-3, GCSF, GRO and iNOS were significantly increased. AXA ameliorated the expression of cas-3, GCSF, GRO, iNOS and MBP. AXA exhibits anti-inflammatory, antioxidant and anti-apoptotic effects on MTX induced toxicity in the cerebral cortex, hippocampus and cerebellar cortex by increasing MBP expression, regulating inflammatory cytokine release and reducing oxidative stress.

Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity.

Objectives: Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity. Materials and Methods: Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days). Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-α (TNF- α) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT. Conclusion: All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.

Protective Effect of Alpha-Lipoic Acid against Liver Damage Induced by Cigarette Smoke: An in vivo Study.

BACKGROUND: Long-term cigarette smoking damages the liver tissue. Alpha-lipoic acid (ALA) is used as a therapeutic agent in a number of conditions and is known to have ameliorative effects against oxidative stress in the liver. OBJECTIVE: To investigate the ameliorative effects of ALA on cigarette smoke (CS)-induced oxidative liver damage by examining histopathological, immunohistopathological changes and biochemical parameters in an animal model. MATERIALS AND METHODS: Twenty-eight female Sprague-Dawley rats were randomly divided into three groups. In the control group (n = 8), rats were exposed to fresh air twice a day and given 0.1 ml of saline by gavage once a day for 8 weeks. In the smoking group (n = 10), rats were exposed to CS for 1 h in the morning and afternoon and given 0.1 ml of saline by gavage once a day for 8 weeks. In the smoking + ALA group (n = 10), CS exposure was same as the smoking group in addition to 100 mg/kg of ALA per day for 8 weeks through gavage. Oxidative damage in the liver tissue was determined by evaluating malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. Aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), direct bilirubin and total bilirubin levels were measured in the blood. Histopathological and immunohistochemical examinations were performed. RESULTS: MDA (P = 0.011), AST (P = 0.018) and total bilirubin levels (P < 0.001) were increased, while CAT activity (P = 0.009) and the efficiency of SOD (P = 0.010) were decreased in the smoking group compared with the control group. CAT activity was increased (P = 0.017) and AST (P = 0.018) and total bilirubin levels (P < 0.001) were decreased in ALA-treated group compared with the smoking group. We observed vascular dilatation and hemorrhagic areas in the smoking group. TNF-α expression was increased in the smoking group compared with the control group. However, TNF-α expression was high in some preparations in the ALA-treated group. CONCLUSIONS: ALA can enhance antioxidant activity, but studies with different doses of ALA are required to determine the extent of its hepatoprotective effect.

The impact of moderate-intensity swimming exercise on learning and memory in aged rats: The role of Sirtuin-1.

OBJECTIVES: The purpose of this study was to evaluate the effect of moderate-intensity swimming exercise on learning and memory by the Morris water maze test. Changes in the expressions of cyclic AMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) proteins alternative pathway which were activated by sirtuin-1 (SIRT-1) were investigated. MATERIALS AND METHODS: The study included thirty-two male Sprague-Dawley rats (350-500 g, 11-12 and 15-16 months old). The rats were randomly divided into four groups with 8 rats in each group. The groups were designed as follows: Control-1 (11-12 months), Exercise-1 (11-12 months), Control-2 (15-16 months), Exercise-2 (15-16 months). Moderate-intensity exercise was assigned for 30 min/day, 5 days/week, for the whole training period of 8 weeks. RESULTS: There were statistically significant differences between the groups on the third day (P=0.005) when swim speeds increased in the exercise groups. There was a statistically significant difference between Exercise 1 and Exercise 2 groups, the entries in the platform zone decreased in Exercise 2 group (P=0.026). While there were no histopathological findings observed in any group, increased SIRT-1, BNDF, and CREB expressions were seen in exercise groups compared with control groups. CONCLUSION: In aged rats exercising at moderate intensity, increased expression of CREB and BDNF, and SIRT-1 could improve hippocampal-dependent memory.

Hippocampus and cerebellum damage in sepsis induced by lipopolysaccharide in aged rats - Pregabalin can prevent damage.

BACKGROUNDS: The aim of this study was to investigate the oxidative damage and inflammatory effects in the hippocampus and cerebellum in lipopolysaccharide (LPS)-induced sepsis model and possible ameliorating effects of pregabalin (PG). METHODS: Twenty four female Wistar Albino rats (12 month old) were divided into 3 groups as follows: Group I (Control; 0.1 ml/gavage and i.p. saline, single dose), Group II (LPS; 5 mg/kg LPS, i.p, single dose), Group III (LPS + PG; 5 mg/kg LPS, i.p, single dose + 30 mg/kg, gavage, single dose). DNA damage, ischemia-modified albumin (IMA), total oxidant status (TOS), total antioxidant status (TAS) oxidative stress index (OSI), leukocyte (WBC), lymphocyte, neutrophil, hemoglobin (HGB), erythrocyte (RBC), and thrombocyte counts were measured in blood and brain tissues. Histopathological and immunohistochemical evaluation of Caspase- 3, G-CSF, IL-6, SAA, iNOS expressions were conducted using hippocampus and cerebellum tissues. RESULTS: Comet analysis score, lymphocytes, neutrophils, WBC, IMA, TOS and OSI values were increased in Group II compared with to Group I (p < 0.05). IMA levels in blood, TOS and OSI levels in the brain were significantly decreased in Group III compared to Group II (p < 0.05). We observed increased hemorrhages, neutrophils, leukocytes infiltrations and neuron degeneration in Group II compared to Group I. Caspase 3, G-CSF, IL-6, SAA, iNOS expressions were increased in group II compared to Group I (p < 0.001). CONCLUSION: Pregabalin partly ameliorated the damage caused by the exposure to LPS in hippocampus and cerebellum; however, further studies are needed to determine pregabalin's possible protective effects at different doses and with different techniques.

Pancreatic damage induced by cigarette smoke: the specific pathological effects of cigarette smoke in the rat model.

In recent years, pancreatic pathologies have become common problems and their etiology and pathogenesis are generally unknown. Studies have shown that smoking may increase the risk of pancreatic disorders but very scant knowledge is available about the pathogenesis of cigarette induced pancreatic pathology. This study aimed to evaluate the oxidative stress status, biochemical, pathological and immunohistochemical findings of rats exposed to cigarette smoke, pathogenesis of smoking related pancreatic damage and usability of Alpha Lipoic Acid (ALA) for amelioration of cigarette smoking induced harmful effects on rat pancreas. Twenty eight female, Sprague Dawley rats were randomly distributed into three groups. The sham group (S) (n = 8), rats were given 0.1 ml of physiological serum by oral gavage for 8 weeks. The cigarette smoke exposed group (CSE) (n = 10), rats were exposed to successive periods of cigarette smoke for 2 hours per day per 8 weeks and given 0.1 ml of physiological serum orally during the study. The cigarette smoke exposed and ALA treated group (CSE + ALA) (n = 10), animals were exposed to cigarette smoke (2 hours per day per 8 weeks) and simultaneously treated with 100 mg per kg per day ALA orally during the study. At the end of the study, the serum samples were collected for insulin, glucagon, glucose and amylase analyses. Tissue samples were collected for biochemical, histopathological and immunohistochemical examinations. Total oxidant status (TOS), total antioxidant status (TAS) levels and oxidative stress index (OSI) were evaluated in the pancreas samples. Immunohistochemical analyses of insulin, glucagon, calcitonin gene related protein (CGRP), active caspase-3, hypoxia inducible factor-1 (Hif-1), Hif-2 and tumor necrosis factor (TNF-α) expressions of pancreas were examined. Cigarette smoke caused statistically significant increase in serum amylase and glucose but decreased insulin levels indicating both endocrine and exocrine cell damage. There were no statistically significant differences in serum glucagon levels between the groups. Histopathological examination of the pancreas exhibited generally normal tissue architecture but slightly degenerative and apoptotic cells were noticed both in the endocrine and exocrine part of the pancreas in the CSE group. Immunohistochemical analyses revealed marked increase in active caspase-3, Hif-1 and Hif-2, CGRP and TNF-α expressions with a slight increase in glucagon immunoreactivity in cells while a marked decrease was observed in insulin expression in some Langerhans islets in the CSE group. ALA ameliorated biochemical and pathological findings in the CSE + ALA group. These findings clearly demonstrated that cigarette smoke can cause damage in both endocrine and exocrine cells in rat pancreas and ALA has an ameliorative effect of cigarette induced lesions.

The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers-The role of gallic acid.

BACKGROUNDS: The aim of this study was to investigate the effects of methotrexate (MTX) on the lung via inflammatory and apoptotic pathway biomarkers and the role of gallic acid (GA). METHODS: In this study, twenty four male Wistar-Albino rats weighing 300-350g were divided into 3 groups as follows; Control group (0.1ml/oral saline, for 7 days+2nd day i.p.). MTX group (20mg/kg, single dose, on 2nd day). MTX+GA group (15mg/kg, orally, for 7 days). Comet analysis, oxidant-antioxidant status, IMA were conducted. Histopathological analyses were evaluated. RESULTS: Comet assay on the blood, TOS and OSI values in the lung were increased in the group II compared with the control group (p<0.05). GA significantly reduced the comet score and IMA levels in the blood, TOS and OSI values in the lung tissue in group III compared with group II (p<0.05). Immunohistochemically PGE2, TNF-α, CRP, serum SAA, Caspase 3 and Caspase 9 expressions significantly increased in group II compared with the control group (p<0.001) and GA treatment ameliorated these parameters significantly in group III compared with group II (p<0.001). CONCLUSIONS: MTX caused oxidative stress and DNA damage in the blood tissue and caused oxidative damage, inflammation and apoptosis in the lung tissue.

The development of large intestine during the fetal period.

OBJECTIVE: The aim of this study is to determine the colon types, developmental change of the colon morphology during the fetal period. METHODS: The study was realised on 131 human fetuses (male 69, female 62) ages between 10 and 40 weeks, which have no external pathology and anomalies. The colon types were evaluated in two parts. As the first part, the colon part between the ileal orifice and sigmoid colon was typed. The sigmoid colon was typed as the second part. The macroscopic diameters of parts of the colon and the thicknesses of wall layers of ascending and descending colons were measured under the light microscope. RESULTS: For the proximal part of the colon, there were seven types of colon, and there were five types for the sigmoid colon. For the first part, transverse type colon was a rare type during the fetal period (3%). The oblique type colon was observed mostly in the first and second trimester during the fetal period. Adult type colon was the most common type in the third trimester and full-term groups. The pendulous type colon was observed mostly in the third trimester. The development of the haustra and tenia coli in the first trimester was quite slow, but later the development increased more and more, and during the full-term period, the haustra and tenia coli could be seen clearly. CONCLUSION: The percentage distribution of the colon types between the trimesters was significant. It was observed that the maturation of haustra and tenia coli started from the ascending colon and progressed towards the sigmoid colon. The thickness of the tunica mucosa layer both in the ascending and in descending colon part increased considerably in the middle of the second trimester.

The development of jejunum and ileum during the fetal period.

OBJECTIVE: In our study, the morphologic structures of the jejunum and ileum sections of small intestine were investigated in human fetuses during the fetal period. MATERIALS AND METHODS: The study was realised on 131 human fetuses (male: 69; female: 62) with ages between 10 and 40 weeks, which have got no external pathology and anomalies. The external sizes of fetuses were measured, and then the structures in the abdominal cavity were determined by the abdominal dissection. The localization of jejunum and ileum, duodenojejunal flexure and ileal orifice points, the measurements of macroscopic diameters, types of the mass of jejunum and ileum and the localization according to the abdominal regions of the mass of jejunum and ileum were determined. Also, the samples of the jejunum and ileum were examined both macroscopically and microscopically. The thickness of tunica serosa, tunica muscularis and tunica mucosa was determined under the light microscope. RESULTS: According to the sexes, gestational ages and groups, the averages and the standard deviations of the all parameters were determined. The correlations between the parameters were determined. The percentage of parameters was compared according to sex and among groups. No differences were found in parameters between sexes (p<0.05). The macroscopic parameters were increased according to the gestational age. The thickness of tunica serosa did not change according to the gestational age. CONCLUSION: It is thought that the data we have will help the evaluation of jejunum and ileum in intrauterine period; we also believe that the data in our study may help in the diagnosis and treatment of anomalies and pathologies in fetal period that belongs to jejunum and ileum.