Cardiac hypertrophy caused by hyperthyroidism in rats: the role of ATF-6 and TRPC1 channels.

Hyperthyroidism influences the development of cardiac hypertrophy. Transient receptor potential canonical channels (TRPCs) and endoplasmic reticulum (ER) stress are regarded as critical pathways in cardiac hypertrophy. Hence, we aimed to identify the TRPCs associated with ER stress in hyperthyroidism-induced cardiac hypertrophy. Twenty adult Wistar albino male rats were used in the study. The control group was fed with standard food and tap water. The group with hyperthyroidism was also fed with standard rat food, along with tap water that contained 12 mg/L of thyroxine (T4) for 4 weeks. At the end of the fourth week, the serum-free triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) levels of the groups were measured. The left ventricle of each rat was used for histochemistry, immunohistochemistry, Western blot, total antioxidant capacity (TAC), and total oxidant status (TOS) analysis. As per our results, activating transcription factor 6 (ATF-6), inositol-requiring kinase 1 (IRE-1), and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and serum-free T3 levels increased, while TAC and TSH levels decreased. With the help of the literature review in our study, we could, for the first time, indicate that the increased activation of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance leads to hypertrophy in hyperthyroidism due to heart failure.

Investigation of the effect of hyperthyroidism on endoplasmic reticulum stress and tran- sient receptor potential canonical 1 channel in the kidney

Background/aim: Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angio- tensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are gluco- se-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods: Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also im- munohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results: TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analy- sis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion: In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

Resveratrol reduces IL-6 and VEGF secretion from co-cultured A549 lung cancer cells and adipose-derived mesenchymal stem cells.

Stem cell therapies are important treatment methodologies used in many areas of experimental or clinical medicine. In recent studies of cancer models, Mesenchymal stem cells (MSCs) suppressed the growth of cancer cells. However, also in some studies, stem cell treatments have been shown to induce cancer formation, increase tumor volume, induce the formation of new vessels, and lead to cancer invasion. The presence of MSC-secreted cytokines and their effects on cancer cells limits the reliability of MSC-based treatments. Resveratrol (trans-3,5,4'-trihydroxystilbene), an antioxidant found in red wine, has been shown to have therapeutic effects against several cancers. The aim of this study was to co-culture MSCs with A549 cancer cells to suppress the release of cancer-promoting cytokines from MSCs and to increase the applicability and reliability of stem cell therapies with resveratrol. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red cell viability assays were used to find safety dose of resveratrol. The MSCs secreted the cytokines IL-6 and VEGF, and the effect of resveratrol on these cytokines was analyzed by ELISA and western blot analysis of conditioned medium. One µM of resveratrol was found to be the safety dose for the A549 cancer cells and MSCs. We observed the highest release of IL-6 and VEGF from the co-cultured A549 cells and MSCs, and resveratrol was found to significantly decrease the release of these cytokines. Our study suggests that resveratrol exerts a positive effect on the release of cytokines. The safety dose of resveratrol can be administered together with stem cells during stem cell treatment.

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects.

Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration.

The effect of di-n-butyl phthalate on testis and the potential protective effects of resveratrol.

This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.

Epiplakin expression dynamics during colon carcinogenesis: Correlation with proliferation.

Colorectal cancer poses a significant global health challenge, with a considerable proportion arising from colon adenomas. Understanding the molecules involved in the carcinogenesis process is crucial for improving colon cancer diagnosis and prognosis. While research on the role of epiplakin in cancer remains limited compared to other plakin group proteins, comprehending its expression patterns and correlations can offer valuable insights into colon carcinogenesis. In this study, we analyzed 60 tissue samples, including colon adenocarcinomas, tubular adenomas (low malignancy risk group), tubulovillous adenomas (high malignancy risk group), and adjacent normal colon tissues. Classification and grading were reevaluated by histological examination. Immunohistochemistry was performed to assess epiplakin and Ki67 expression. Epiplakin optical density and the Ki67 proliferation index were calculated using ImageJ. Statistical analyses were conducted to evaluate correlations and significance. Epiplakin expression was significantly decreased in colon adenocarcinomas [optical density median 4.04 (95% CI, 3.98 to 4.24)] and tubulovillous adenomas [4.32 (95% CI, 4.08 to 4.32)] compared to normal colon tissues [4.61 (95% CI, 4.50 to 4.67)] and tubular adenomas [4.87 (95% CI, 4.67 to 4.88)] (P < 0.05). Moreover, adenoma groups exhibited higher proliferation indices (P < 0.05), and a positive correlation was found between epiplakin expression and the Ki67 proliferation index (r = 0.317, P < 0.05). Our study highlights the potential significance of epiplakin in colorectal cancer. Decreased epiplakin expression is associated with colon malignancy progression, suggesting its role as a potential marker.

Selenomethionine, a Trace Element, Increases Osteoblastic Activity of hFOB 1.19 Cells (an In Vitro Study).

Osteoporosis and resulting fractures affect a significant group of people in the world. It has been shown in many studies that selenium has positive effects on bone metabolism. Based on this information, the aim of this study is to investigate whether bone differentiation will start in a shorter time by applying selenomethionine (SeMet) to hFOB cells.First, hFOB 1.19 cells were cultured. Safe doses of SeMet were determined by MTT and LDH tests. Ossification levels were determined by alizarin red staining and measurement of alkaline phosphatase enzyme levels. The results were analyzed with statistical tests.It was observed that SeMet increased cell viability at concentrations of 10, 25, 50, 100, and 200 µM in 24 h. At these concentrations, cell viability increased above the control, the viabilities were as follows: 109.4%, 104.9%, 104.3%, 103.15%, and 100.27%. High doses of SeMet significantly reduce cell viability. According to Alizarin red staining, SeMet increases the amount of calcium deposits in hFOB cells in a dose-dependent manner. In the experimental groups, the highest ALP enzyme was determined in the 7-day SeMet application. The most effective dose was measured as 15 µM.It was determined that SeMet, which is found as a trace element in living things in nature, increases the viability of hFOB cells, which are osteoblast cell precursors, and increases osteoblastic differentiation and osteoblastic activity in these cells. Our results are at a level that sheds light on an important problem in public health.

Comparison of nephrostomy drainage types following percutaneous nephrolithotomy requiring multiple tracts: single tube versus multiple tubes versus tubeless.

OBJECTIVES: Placement of multiple nephrostomy tubes is the standard practice after completion of multitract percutaneous nephrolithotomy (PCNL) to reduce hemorrhage and urinary extravasation.We compared the outcomes among tubeless, single nephrostomy drainage and multiple nephrostomy drainage tubes following PCNL requiring multiple tracts. METHODS: We retrospectively analyzed the data of 115 patients who underwent PCNL using multiple (two or more) access tracts. Patients were categorized into three groups: one nephrostomy tube for each tract (group 1, n = 43); single nephrostomy tube placement (group 2, n = 51), and no nephrostomy drainage with antegrade placement of a double-J stent (group 3, n = 21). RESULTS: The three groups had comparable demographic data. The differences in operative times, average hemoglobin decrease and complication rates for the three groups were not statistically significant. The average hospital stay in the tubeless group (mean 2.1 days) was significantly shorter than that in group 1 (4.2 days) and group 2 (3.5 days). The postoperative analgesic requirement was significantly higher in group 1 compared to group 2 (p < 0.05) and group 3 (p < 0.001). Stones were completely cleared in 83.7, 84.3 and 85.7% of patients, which increased to 90.7, 92.1, and 95.2% with adjunctive therapies in groups 1, 2 and 3, respectively. CONCLUSIONS: Single or no nephrostomy drainage following multitract PCNL offers the potential advantages of decreased postoperative analgesic requirement, and hospital stay without increasing the complications.

ß-Hydroxybutyrate, One of the Three Main Ketone Bodies, Ameliorates Acute Pancreatitis in Rats by Suppressing the NLRP3 Inflammasome Pathway.

BACKGROUND: Acute pancreatitis (AP) is a widespread disease resulting from the inflammation of acinar cells in the pancreas. ß-hydroxybutyrate (BHB) is a water-soluble main ketone body synthesized in the human liver. The purpose of this study was to examine the possible therapeutic effects of BHB in the experimentally-induced AP model in rats. METHODS: In our study, male rats were randomly allotted into 6 groups, as control (0.9% saline i.p.), BHB1 (200 mg/kg BHB i.p.), BHB2 (2 doses of 200 mg/kg BHB i.p.), AP (4 doses of 50 µg/kg cerulein i.p., 4 doses at 1 h intervals), AP+BHB1 and AP+BHB2 groups. In pancreatic tissue sections, immunohistochemistry staining and western blot analysis for the inflammasome complex (caspase-1, ASC, and NLRP3) and inflammation-associated proteins (TNF-α and NF-κB) and a histopathological examination were performed. The levels of lipase, amylase, interleukin (IL)-18 and IL-1ß in serum were measured. RESULTS: Several pathological degenerations, including edema, inflammatory cell infiltration, acinus necrosis, and bleeding were observed in the AP group, while the histological architecture of the control and the sham BHB1 and BHB2 groups were regular. The AP-induced pathological changes were considerably alleviated in the AP+BHB1 and AP+BHB2 groups. In the AP group, a conspicuous increase in caspase-1, ASC, NLRP3, TNF-α, and NF-κB proteins, and in the levels of amylase, lipase, IL-18, and IL-1ß were detected. BHB treatments after AP induction decreased those proteins to the level of control. CONCLUSIONS: We demonstrated that BHB has the potential to cure AP by suppressing the NLRP3 inflammasome and can be used in the treatment of many diseases which progress through the NLRP3 inflammasome.

Investigation of endoplasmic reticulum stress and sonic hedgehog pathway in diabetic liver injury in mice.

AIMS: Diabetes is a common metabolic disease which damages many organs including the liver and causes endoplasmic reticulum (ER) stress, which originates from non-folded proteins. Sonic hedgehog (Shh) pathway plays a role in liver regeneration and repair. To our knowledge, there is no study showing the relation between ER stress and Shh pathway in the liver in diabetes. Thus, the aim of this study was to investigate the interaction between ER stress and Shh pathway in the liver of diabetic mice. MAIN METHODS: Six groups of male mice were formed as control, diabetes (streptozotocine-treated), Shh activator (SAG-treated), Shh inhibitor (SANT1-treated), diabetes + SAG and diabetes + SANT1. At the end of the experiment, mice were weighed, anaesthetized and euthanized. Blood samples were collected, livers were excised and weighed. Thereafter, blood glucose, serum ALT and AST levels, TOS and TAC levels in liver tissue were measured. ER stress marker (GRP78) and Shh pathway molecules (Gli1 and Smo) were evaluated by immunohistochemistry, H-score and western blot analyses. Besides, histopathological examination was performed. KEY FINDINGS: Results showed that GRP78, Gli1 and Smo were increased in liver due to Type 1 diabetes. The SAG agent decreased GRP78 and increased Gli1 and Smo, leading to liver repair, while the inhibitor SANT1 increased GRP78 and decreased Gli1and Smo, causing progression of the liver stress induced by diabetes. SIGNIFICANCE: In conclusion, the Shh pathway is related to ER stress and may provide a new strategy for its treatment, especially liver stress induced by diabetes.

Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice.

Nonalcoholic fatty liver disease (NAFLD) is an important health problem. The prevalence of NAFLD is increasing, especially in the Western countries. Although there are several intracellular pathways in NAFLD, endoplasmic reticulum (ER) stress has recently gained importance. Silymarin is an important liver-protective biological molecule. In light of this information, we investigated mice for the effect of silymarin on ER stress in the NAFLD model. In our study, the mice were randomly divided into six groups: Control, silymarin 100 and 200 mg/kg sham, fructose-induced NAFLD, and NAFLD + silymarin groups. After the last administrations, liver and blood samples were taken and hematoxylin-eosin, as well as Oil red O staining, were performed. As a result, the body and liver weights, lipid profile, AST, ALT, and glucose levels, along with the ER stress markers, increased in the NAFLD-only group. Silymarin treatments reversed most of these changes. Particularly, 200 mg/kg silymarin was more effective. PRACTICAL APPLICATIONS: According to the results, silymarin attenuated NAFLD by decreasing the ER stress proteins GRP78 and XBP-1. Silymarin may be therapeutic in the treatment of NAFLD as well as other ER-stress-based diseases. Silymarin can also be taken with food for prophylactic purposes.

Mirtazapine may show anti-hyperglycemic effect by decreasing GLUT2 through leptin and galanin expressions in the liver of type 1 diabetic rats.

OBJECTIVES: The aim of this study was to explore the molecular mechanism of mirtazapine with respect to energy metabolism in Streptozotocin-induced diabetic liver of rats by immunohistochemistry and Western blot. MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were assigned into 3 groups including control, type 1 diabetes mellitus (T1DM) group (55 mg/kg Streptozocin, IP) and T1DM+mirtazapine (20 mg/kg,PO) group. At the end of the experiment, blood glucose levels were measured and liver tissues were stained by Periodic acid-Schiff. Moreover, leptin and glucose transporter 2 (GLUT2) proteins were analyzed by western blot and immunohistochemistry; however, galanin were analyzed only by immunohistochemistry. RESULTS: At the end of the study, in diabetes group, blood glucose level, GLUT2 and galanin expressions increased, while leptin expression decreased when compared to control group. Mirtazapine treatment restored the decreased leptin expression, and the increased blood glucose level and galanine expression to the level of the control group. It also decreased the GLUT2 expression even below the control group. CONCLUSION: We concluded that mirtazapine may show its anti-hyperglycemic effect by decreasing GLUT2 through altering the leptin and galanin expression in the liver of type 1 diabetic rats. Mirtazapine can be used as an antidepressant for T1DM patients and as a drug to reduce blood glucose level in T1DM.

Azoramide ameliorates fructose-induced nonalcoholic fatty liver disease in mice.

Nonalcoholic fatty liver disease (NAFLD) is a frequent health problem. The insulin resistance and endoplasmic reticulum (ER) stress have been suggested to play important roles in the development and progression of NAFLD. However these processes and correlations have not fully been understood yet. Azoramide, an antidiabetic drug, has the potential for reducing insulin resistance and ER stress in obese mice. To date, there is no study on the effects of azoramide in NAFLD. The aim of this study was to investigate the potential role of azoramide on insulin resistance and ER stress in NAFLD induced mice. Forty Swiss Albino mice were assigned into control, azoramide, fructose and fructose + azoramide groups. Azoramide group received a single dose of azoramide at 150 mg/kg/day by gavage between 71-77th days. Fructose group was treated with 30% fructose solution for 70 days to generate NAFLD. Fructose + azoramide group was treated with 30% fructose for 70 days and then with a single dose of 150 mg/kg/day azoramide for 7 days. At the end of experiment, blood of mice was taken via cardiac puncture, and the livers were excised and weighted. GRP78 and XBP-1 levels were examined with immunohistochemistry in liver tissues. Liver steatosis was evaluated with H&E, Oil-Red O and Sudan-Black staining. ALT, AST, triglyceride, total cholesterol, VLDL, LDL, HDL, fasting glucose and insulin levels were measured in serum. The body and liver weights, insulin resistance, ER-stress markers, lipid profile, AST, ALT and histopathological changes increased by fructose treatment. Azoramide treatment was generally reversed all these changes. These data offer the first evidence to show that azoramide may serve as a potential treatment agent in NAFLD through decreasing the ER-stress and insulin resistance.

Mirtazapine suppresses sterile inflammation through NLRP3-inflammasome in diabetic rat kidney.

AIM: The aim of this study was to investigate the effects of mirtazapine, which is anti-oxidative and antidepressant agent, on the kidney damage caused by diabetes mellitus. MATERIALS AND METHODS: The rats were randomly divided into three groups (n = 7 animals in each group). The group I rats served as control and they received 0.1 mol/L of citric acid buffer (pH = 4.5) as vehicle. The rats in the group II (DM group) and III (DM + Mirtazapine-treated group) were treated intraperitoneally with a single dose of 55 mg/kg streptozotocin dissolved in 0.1 mol/L of citric acid buffer. Group III rats were also received 20 mg/kg/day of mirtazapine for 2 weeks. At the end of the experiment, the rats were sacrificed. Then, the kidneys were excised and prepared for microscopical examination. caspase-1 and NLRP3 proteins were examined using immunohistochemistry and western blotting. The TUNEL assay for apoptosis and ELISA assay for IL-1ß were performed. RESULTS: Histological examination showed that mirtazapine administration has an ameliorative effect on DM-induced kidney damage. Immunohistochemical and western blot analyses showed that NLRP3 and caspase-1 expressions were increased in the DM group according to the control group and the mirtazapine administration decreased these expressions. The intraglomerular and tubular TUNEL-positive cells were numerous in the DM group compared to the mirtazapine-treated group. The level of IL-1ß was highest in the DM group, and decreased significantly in the mirtazapine-treated group. CONCLUSION: In this study, 20 mg/kg/day mirtazapine administration for 2 weeks reduced NLRP3 and caspase-1 expressions and IL-1ß level in the diabetic rat kidneys. These results suggesting that mirtazapine may be useful in the treatment of DM and other metabolic diseases. Advanced molecular studies are needed to elucidate the exact effects of mirtazapine on NLRP3 inflammasome.

Beneficial effect of mirtazapine on diabetes-induced hyperalgesia: involvement of TRPV1 and ASIC1 channels in the spinal cord and dorsal root ganglion.

OBJECTIVES: Neuropathic pain reduces the life qualities of patients with Diabetes mellitus. Clinical guidelines recommend relief in diabetic neuropathic pain through the use of some antidepressants, anticonvulsants, opioids as well as capsaicin cream or lidocaine patches. However, since the majority of patients do not or partially respond to current treatments, there is a growing necessity for new drugs increasing the pain relief in patients with diabetes. Therefore, based on the therapeutic potential of antidepressants on neuropathic pain, we investigated the promising antihyperalgesic effect of mirtazapine (MRT) in painful diabetic neuropathy. METHODS: Experimental diabetes was induced in rats by single intraperitoneal injection of 55 mg/kg dose of streptozocin (STZ). After 4 weeks of injection of STZ, MRT was administrated for 14 days at 40 mg/kg dose. Randall-Selitto and Hargreaves tests were applied for paw-withdrawal threshold and paw-withdrawal latency measurement. TRPV1 and ASIC1 expressions measured by Western blot in dorsal root ganglion and spinal cord. RESULTS: Administration of MRT significantly improved both of the decreased paw-withdrawal threshold and shortened the paw-withdrawal latency of diabetic rats, respectively. Besides, increased levels of TRPV1 and ASIC1 channels in dorsal root ganglion and spinal cord of diabetic rats, evaluated by Western blot method, were decreased following the MRT treatment. DISCUSSION: These data show, for the first time, that MRT has beneficial effects against diabetes-induced hyperalgesia, and that suppressive effect of this drug on TRPV1 and ASIC1 levels, which are increased in diabetic rats, may be some of the pharmacological mechanisms underlying the exhibited antihyperalgesic effect of MRT.

The effect of sulfur dioxide inhalation on active avoidance learning, antioxidant status and lipid peroxidation during aging.

The effect of SO2 was examined on active avoidance learning, thiobarbituric acid reactive substances (TBARS), and the activities of Cu, Zn superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in young (3 months), middle-age (12 months ), and old (24 months) Swiss male albino rats. Ten ppm SO2 was administered to the animals of SO2 groups in an exposure chamber for 1 h/day x 7 days/week x 6 weeks while control groups were exposed to filtered air in the same condition. The most prominent effect of aging on active performance was also observed in the older group. SO2 exposure significantly decreased the active avoidance learning in the young group, but it had no effect on this parameter in the middle-aged and the older group compared with their corresponding control groups. SO2 exposure resulted in increased levels of Cu, Zn-SOD activity while decreased level of GSH-Px activity in all experimental groups compared with their corresponding control groups. CAT activities were unaltered. TBARS levels of all SO2 exposed groups were significantly increased compared with their respective control groups. In conclusion, results from the present research showed that SO2 exposure resulted in an increase in the lipid peroxidation and caused alterations in antioxidant enzyme activities. Additionally, SO2 exposure impaired cognitive function only in the young rats during the acquisition phase of active avoidance learning.

Neuroprotective Effect of Genistein in Peripheral Nerve Injury.

AIM: To investigate the effects of genistein in a rat model of sciatic nerve crush injury and complete sciatic nerve transection. The effects of genistein were compared with those of gabapentin, which is widely used in clinical practice for peripheral nerve injury. MATERIAL AND METHODS: Forty-eight rats were randomly divided into six groups (8 rats in each group): group 1 (sham); group 2, sciatic nerve crush injury (control); group 3, sciatic nerve crush injury+genistein 20 mg/kg; group 4, sciatic nerve crush injury+gabapentin 90 mg/kg; group 5, sciatic nerve transection+genistein 20 mg/kg; group 6, sciatic nerve transection+gabapentin 90 mg/kg. The effects of genistein and gabapentin were assessed with immunohistochemical staining for growth associated protein-43 (GAP-43) and myelin basic protein (MBP). Interleukin-1ß and tumor necrosis factor α levels in the injured nerve specimens were assessed as a measure of inflammatory response; walking track analysis and sciatic function index for neurological recovery and the paw mechanical withdrawal threshold were examined for neuropathic pain. RESULTS: On histopathological examination, genistein use was associated with a greater immunoreactivity for GAP-43 and MBP compared with that associated with gabapentin. Genistein and gabapentin had similar effects on anti-inflammatory activity, functional recovery, and neuropathic pain. CONCLUSION: Genistein and gabapentin exhibit positive effects on histopathology, inflammation, and clinical findings of peripheral nerve injury. When the systemic side effects of gabapentin are considered, genistein (a basic soy isoflavone that has no side effects) can be used as an alternative to medical treatment in peripheral nerve injury.

Protective effects of resveratrol against di-n buthyl phthalate induced toxicity in ductus epididymis and ductus deferens in rats.

OBJECTIVE: This study aimed to observe the possible protective effects of resveratrol (RSV) against damage induced by di-n-butylphthalate (DBP), on the ductus epididymis and deferens in rats. MATERIALS AND METHODS: Six groups of rats were used in the experiment: Group 1: Control group; Group 2: Solvent (carboxymethylcellulose (CMC), 10 ml/kg); Group 3: 500 mg/kg/day DBP; Group 4: 500 mg/kg/day DBP+20 mg/kg/day RSV; Group 5: 1000 mg/kg/day DBP; Group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Immunohistochemical, electronmicroscopic and histomorphometric examinations were carried out in the epididymis and deferens. RESULTS: In the ductus epididymis and deferens mitochondrial crystolysis, exfoliation of the stereocilia and openings in lateral surface increased with DBP dosage, but these structures were recovered with RSV. DBP reduced the epithelial height of epididymis and vas deferens. Lumen dilatation was observed in both tissues. These disorders may lead to dysfunction of epithelial absorption. In the TUNEL examinations in both tissues, there were no apoptotic cells or apoptotic bodies. CONCLUSION: In conclusion, DBP administration caused structural degeneration in the epididymis and deferens, parallel to dose evaluation and RSV can reverse these changes with its protective effects.