Lercanidipine alleviates doxorubicin-induced lung injury by regulating PERK/CHOP and Bax/Bcl 2/Cyt c pathways.

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model.

Investigation of the effects of astaxanthin in experimental polycystic ovary syndrome (PCOS) in rats.

Objectives: The aim of this study was to investigate the effect of Astaxanthin (ASX) on ovaries in letrozole-induced polycystic ovary syndrome (PCOS) model in female rats by histopathological, immunohistochemical and biochemical techniques. Materials and Methods: Seventy two Sprague-Dawley female rats with an average weight of 200-250 gr and 10-12 weeks old were randomly divided into 9 groups. PCOS model was applied to all groups except healthy group. In the study, low (10 mg / kg) moderate (20 mg / kg) and high (40 mg / kg) doses of ASX were given to the experimental animals in the PCOS-induced groups for 7 days. At the end of the experiment, ovarian tissues were evaluated histopathologically, immunohistochemically, and biochemically. Results: When the histopathological findings were examined, many cystic follicles, apoptotic and necrotic cells were found in the follicles in the PCOS group. In addition, significant decrease in apoptotic and necrotic cells were observed in PCOS+MET+ASX and PCOS+ASX groups. In immunohistochemical staining findings, while TNF-α NF-κB and IL-6 expression levels showed significant increase in PCOS group, these expression levels were decreased in PCOS+MET+ASX and PCOS+ASX groups. In the biochemical evaluations, while MDA were increased, SOD were decreased in the PCOS group. MDA level were decreased while SOD levels were increased in the PCOS+MET+ASX and PCOS+ASX groups. Conclusion: In addition to the formation of insulin resistance in the tissue, severe oxidative stress damage occurs in ovarian tissue during PCOS. Metformin improved PCOS by correcting insulin resistance. In this period, the administration of ASX with Metformin protected the ovary from oxidative stress damage.

Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study.

The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole. Sperm parameters were significantly impaired in all antipsychotics-treated groups. Haloperidol and Risperidone significantly decreased the level of testosterone. All antipsychotics had significantly reduced inhibin B level. A significant reduction was observed in SOD activity in all antipsychotics-treated groups. While GSH levels diminished, MDA levels were rising in the Haloperidol and Risperidone groups. Also, the GSH level was significantly elevated in the Quetiapine and Aripiprazole groups. By causing oxidative stress and altering hormone levels, Haloperidol and Risperidone are damaging to male reproductivity. This study represents useful starting point for exploring further aspects of the underlying mechanisms reproductive toxicity of antipsychotics.

Nicotinamide Riboside Preserves Ovarian Injury in Experimental Sepsis Model in Rats.

OBJECTIVE: The aim of the study is to investigate the protective effects of nicotinamide riboside on oxidative stress in an experimental sepsis model created by cecal ligation and puncture. MATERIALS AND METHODS: Rats were divided into 3 groups randomly: sham-operated (control) group, sep- sis group, and nicotinamide riboside-treated group. Sepsis model-induced cecal ligation and puncture was applied to sepsis group rats. Animals in the nicotinamide riboside-treated group were administered nicotin- amide riboside intraperitoneally (500 mg/kg). Tissue specimens from rats were biochemically calculated for their activities of catalase, superoxide dismutase, glutathione peroxidase, myeloperoxidase, and malondialde- hyde levels. Ovarian tissues of all rats were histopathologically evaluated. RESULTS: Catalase, superoxide dismutase, and glutathione peroxidase activities were lower in the sepsis group compared to the sham-operated (control) group. Superoxide dismutase activity was significantly higher in the nicotinamide riboside-treated group than in control and sepsis group (P <.05). Myeloperoxidase activi- ties and mean malondialdehyde concentration of ovarian tissue were lower in nicotinamide riboside-treated group than in sepsis group (P<.05). The light microscopic assessment revealed that ovarian tissue was protected, and inflammation and interstitial edema decreased in nicotinamide riboside-treated group. The follicular damage findings were notably decreased in nicotinamide riboside-treated group in comparison to sepsis group (P<0.05). CONCLUSION: Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibiting tissue infiltration and increasing endogenous antioxidant capacity. Nicotinamide riboside administration may represent a new treatment approach for the prevention of sepsis-induced ovarian injury.

Potential protective effect of astaxanthin on ovary ischemia-reperfusion injury.

Objectives: We thought that astaxanthin (ASX) might be a protective agent in oxidative stress damage that develops against ischemia and reperfusion injury in the rat ovary. Materials and Methods: The experimental groups consisted of healthy, I (Ischemia), I+ASX50, I+ASX100, I/R (Ischemia/Reperfusion), I/R+ ASX50, and I/R+ ASX100. Vascular clamps were applied to the ovaries for 3 hr to induce ischemia. For the reperfusion groups, the clamps were opened and blood flow was restored to the ovaries for 3 hr. At the end of the experiment, biochemical, histopathological, and immunohistochemical analyses were made from the tissue samples taken. Results: While MDA levels increased significantly in I and I/R groups, SOD levels decreased. It was found that ASX significantly decreased MDA levels and increased SOD activity in treatment groups depending on the dose. Caspase 3, IL-1 ß, and IL-6 expressions were severely increased in ischemia and I/R groups, while the severity of I+ASX50 and I/R+ASX100 immunoreactivity was decreased. While severe hemorrhage areas were observed in I and IR groups, minimal hemorrhage areas were observed in the treatment groups, especially in I/R+ASX100 groups. In addition, inflammatory cells and necrotic cells in the I/R group were not observed in I/R+ASX50 and I/R+ASX100 groups. Conclusion: As a result, it was determined that ASX has a strong protective role against oxidative damage in the treatment of ovarian ischemia-reperfusion injury.

Histopathological Overview of Experimental Ulcer Models.

Histopathology is the process of examining tissue that includes all the changes, when a diseased tissue shows compared to a healthy group with a result of a histological observation. Histopathology has become an essential process in medical experimental research and medical experimental models. Scientists have developed medical experimental animal models for these reasons and have pioneered new drug research for many years. One of these experimental researches is experimental ulcer models. This model, which was initially a single method, has led to the emergence of new models with the discovery of physiological processes on ulcers by scientists. Nowadays, researchers have performed many new peptic ulcer models on experimental animals over the years. The main point in the creation of the ulcer model is the increase in the stomach acid level and the removal or corruption of the gastric mucus. When the experimental models were examined histopathologically, it was seen that the most severe models were those induced by pyloric ligation, acetic acid application, and indomethacin. In these models, ulcer foci that progressed to the submucosa were common, while the superficial damage spreading to the entire surface was striking in the ethanol model. While epithelial losses are shown on the surface of the mucosa, foci of necrotic apoptotic cell clusters extending to the submucosa are shown according to the weight of the model. In addition, evidence of inflammation has been shared in almost all studies. All these results show that ulcer models can be created by many different mechanisms. However, similar findings were observed in almost all experiments. Whether the experimental model caused severe or mild ulceration changed the histological findings.

A novel effect of Aprepitant: Protection for cisplatin-induced nephrotoxicity and hepatotoxicity.

Cisplatin is widely used chemotherapeutic drug and have some serious side effects as tissue toxicity and nausea and vomiting. Aprepitant is used in clinic as an anti-emetic drug for cisplatin treated patient to prevent nausea and vomiting. We aimed to investigate the protective effects of Aprepitant on cisplatin-induced nephrotoxicity and hepatotoxicity. In total 42 male rats were separated into six groups (n = 7). A single dose of cisplatin (10 mg/kg i.p.) was administered to induce toxicity on first day. Different doses of Aprepitant (5, 10 and 20 mg/kg, p.o.) were given to treatment groups during 3 days. After the experimental procedures serum enzymes (ALT, AST, ALP, BUN and Creatinin), kidney and liver oxidative parameters (SOD, GSH and MDA), inflammatory cytokines (TNF-α and NF-κB) and Cyp2e1 expressions analyzed. Histopathological investigations also performed for all groups. Cisplatin caused tissue toxicity in both kidney and liver. Serum enzymes, tissue cytokines and oxidative stress were increased after the Cis treatment. Aprepitant treatment normalized all parameters compared to cisplatin treated group. Cisplatin significantly increased the Cyp2e1 expression in the kidney while significantly decreased in the liver compared to Healthy group. Histopathologically, it was shown that cisplatin causes a lot of abnormal structures as inflammatory infiltration and necrosis on the liver and kidney. Similar the biochemical and molecular results, aprepitant showed positive effects on tissue pathological parameters. With its main anti-emetic effect, Aprepitant treatment may be an effective option for cancer patients if they have additional injury as nephrotoxicity and hepatotoxicity due to cisplatin.

Effects of soy isoflavonoids (genistein and daidzein) on endometrial receptivity.

OBJECTIVES: This study aimed to examine the effects of genistein and daidzein on endometrial receptivity by histopathological, immunohistochemical, and biochemical techniques. MATERIALS AND METHODS: In this study, 72 female Sprague-Dawley rats were randomly divided into 8 groups. The endometrial receptivity model was applied to identified groups. Experimental animals were given periorally 10 mg/kg and high 40 mg/kg doses of genistein and daidzein for 5 days by gavage. At the end of the experiment, uterine tissues were evaluated histopathologically, immunohistochemically, and biochemically. RESULTS: When histopathological findings were examined, significant decreases in pinopod formation were observed in high dose genistein and daidzein groups. When compared with the endometrial receptivity group, immunohistochemical staining findings showed a significant decrease in the expression of integrin ß3, integrin αvß3, LIF, and HOXA10 and an increase in MUC 1 expression in the high dose of genistein and daidzein groups. In biochemical evaluations, it was determined that genistein and daidzein increased estrogen levels and decreased progesterone levels in a dose-dependent manner. CONCLUSION: Genistein and daidzein have a negative effect on endometrial receptivity. Therefore, individuals with a risk of infertility should pay attention to the consumption of genistein and daidzein.

Effects of immunosuppressive drugs on oral mucosa in patients with Behçet's disease: cytomorphological and cytopathological assessment.

BACKGROUND/AIM: The aim of this study was to investigate cytomorphological and cytopathological changes in oral exfoliated smears collected from immunosuppressed patients with Behçet's disease (BD) using stereological methods. MATERIALS AND METHODS: For cytomorphometric analysis, mucosal cell smears were obtained from the buccal mucosa and the floor of the mouths of BD patients treated with immunosuppressive drugs and from healthy volunteers. All mucosal smears from the patients and the healthy volunteers were stained using the Papanicolaou method and examined cytopathologically under light microscopy and cytomorphologically via the stereological nucleator method. RESULTS: The cytomorphological analysis revealed 3 types of mucosal cells, with numbers of particularly pink cells lower in the aphthous areas of the patients with BD compared to the healthy controls (P < 0.05). The nuclear volumes (NVs) and cytoplasmic volume (CVs) were significantly higher in the BD patients (P < 0.05), but the NV/CV ratio was higher only in the drug-use patient groups (P > 0.05). There was lower apoptotic activity in the nondrug-use patients with BD and in the immunosuppressive-taking BD patients. CONCLUSION: The findings suggest that quantifiably morphological and morphometric changes in oral mucosa can be detected by stereological techniques. Changes in these parameters may indicate malignant transformation in the oral mucosa.

Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: an ultrastructural study.

PURPOSE: Symptoms and disorders related to menopause and its associated estrogen deficiency have become a considerable health concern worldwide. Ovarian hormone depletion/estrogen deficiency can be usefully studied using animal models after removal of the ovaries [ovariectomy (Ovx)]. This study assessed renal changes after Ovx-induced estrogen deficiency in a rat model. METHODS: Rats were randomly allotted into one control group (group I, healthy) and three study groups (group II, Ovx group; group III, Ovx +17ß-estradiol group; and group IV, Ovx + bortezomib group). RESULTS: In the Ovx group (group II), thickening of glomerular capillary walls, narrowing of Bowman's capsular space, glomerular hypertrophy, atrophic tubules, and loss of the basal membranes of the tubules were observed. Mesangial cell proliferation was observed, particularly in the glomerulus. Immunohistochemical (IHC) staining studies in this group showed dense staining in the mesangial cells, tubular cell Nf-KB/p65, and caspase-3. Groups III and IV (Ovx +17ß-estradiol and Ovx + bortezomib) showed decreased NF-kB/p65 and caspase-3 expression compared with the Ovx group (p < 0.05). CONCLUSION: In renal failure related to estrogen deficiency caused by Ovx, 17ß-estradiol and bortezomib have a protective effect on renal tissue.

Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study.

Decline of estrogen during menopause has been associated with numerous significant changes that have been linked to many pathophysiological complications. In addition, ovarian hormone deficiency increases the production of reactive oxygen radicals which could result in oxidative stress and cell damage. While estrogen therapy is often considered to overcome the behavioral and physiological shortcomings, antioxidants are gaining popularity for their beneficial property. For this purpose, in the present study, utilizing the antioxidant properties of beta glucan has been examined in treatment of menopause induced oxidative stress in cerebral neurons. Four groups of female Wistar rats were used: control, ovariectomy, ovariectomy + estrogen treated and ovariectomy + beta glucan treated. We observed a significant increase in neural degeneration in ovariectomized rats as compared to controls. Moreover, increased oxidative stress in the brains of the ovariectomized rats has been detected by performing immunohistochemical analysis. A large number of immuno-positive cerebral neurons have been observed in ovariectomy group rat brains. Interestingly, providing beta glucan treatment to ovariectomized rats reduced the number of degenerated neurons. Our study is the first to examine light and electron microscopic examination and immunohistochemical and stereological analysis of estrogen depletion in rats and to test protective role of beta glucan in the experimental study.

Effects of Diabetes on Post-Menopausal Rat Submandibular Glands: A Histopathological and Stereological Examination.

OBJECTIVE: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models. MATERIALS AND METHODS: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups. RESULTS: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups. CONCLUSION: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation.

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.

The effect of estrogen usage on eccentric exercise-induced damage in rat testes.

BACKGROUND: Recent years, lots of scientific studies are focused on the possible mechanism of inflammatory response and oxidative stress which are the mechanism related with tissue damage and exercise fatigue. It is well-known that free oxygen radicals may be induced under invitro conditions as well as oxidative stress by exhaustive physical exercise. OBJECTIVES: The aim of this study was to investigate the effects of anabolic steroids in conjunction with exercise in the process of spermatogenesis in the testes, using histological and stereological methods. MATERIALS AND METHODS: Thirty-six male Sprague Dawley rats were divided to six groups, including the control group, the eccentric exercise administered group, the estrogen applied group, the estrogen applied and dissected one hour after eccentric exercise group, the no estrogen applied and dissected 48 hours after eccentric exercise group and the estrogen applied and dissected 48 hours after eccentric exercise group. Eccentric exercise was performed on a motorized rodent treadmill and the estrogen applied groups received daily physiological doses by subcutaneous injections. Testicular tissues were examined using specific histopathological, immunohistochemical and stereological methods. Sections of the testes tissue were stained using the TUNEL method to identify apoptotic cells. Apoptosis was calculated as the percentage of positive cells, using stereological analysis. A statistical analysis of the data was carried out with one-way analysis of variance (ANOVA) for the data obtained from stereological analysis. RESULTS: Conventional light microscopic results revealed that testes tissues of the eccentric exercise administered group and the estrogen supplemented group exhibited slight impairment. In groups that were both eccentrically exercised and estrogen supplemented, more deterioration was detected in testes tissues. Likewise, immunohistochemistry findings were also more prominent in the eccentrically exercised and estrogen supplemented groups. CONCLUSIONS: The findings suggest that estrogen supplementation increases damage in testicular tissue due to eccentric exercise.

The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular Torsion Injury in Rats.

PURPOSE: Testicular torsion is a urological emergency. Failure of timely intervention for this issue leads the testicles to go into necrosis. If left untreated, it can lead to loss of the reproductive organs. The aim of this study was to examine the role of aliskiren in testicular torsion and detorsion injuries. MATERIALS AND METHODS: Rats were divided into 8 groups of 12 each, including no torsion-detorsion, no torsion-detorsion plus 200 mg/kg aliskiren orally, torsion, torsion-detorsion, torsion plus 100 mg/kg aliskiren orally, torsion plus 200 mg/kg aliskiren orally, torsion-detorsion plus 100 mg/kg aliskiren orally and torsion-detorsion plus 200 mg/kg aliskiren orally. Aliskiren was administered 30 minutes before ischemia and reperfusion, and also 24 hours before the experimental protocol in all treatment groups. Ischemia and reperfusion were each applied for 2 hours. RESULTS: Testicular damage decreased superoxide dismutase and glutathione, and increased malondialdehyde in the testis tissues of rats. Aliskiren administration increased superoxide dismutase and glutathione, and decreased malondialdehyde in the testis tissues. Values were measured by a biochemical autoanalyzer. In addition, this torsion-detorsion damage caused a significant increase in levels of the inflammatory cytokine and agents interleukin-1ß and inducible nitric oxide synthase, as examined by real-time polymerase chain reaction. Aliskiren administration decreased these parameters. On pathological evaluation administration of a 200 mg/kg dose of aliskiren was found to protect the testis. Renin-angiotensin-aldosterone system inhibition by aliskiren caused an increase in serum renin levels and a decrease in serum angiotensin II levels. CONCLUSIONS: It appears that aliskiren protects the testis from ischemia-reperfusion damage by regulating inflammation and the oxidant-antioxidant balance via renin-angiotensin-aldosterone system inhibition.

Hepatoprotective effect of 17ß-estradiol as antioxidant modulators against stress damage.

BACKGROUND: Liver is one of the most important organs affected by exercise. According to the literature a few study to date has investigated the effects of estrogen supplementation on exercise-induced oxidative stress in liver tissue of rats. OBJECTIVES: We aimed to investigate the effects of estrogen supplementation on oxidative stress markers in liver tissue of exercised rats. MATERIALS AND METHODS: Male rats (n = 35) were divided as estrogen supplemented (n = 18) and non-supplemented groups (n = 17); these groups were further divided as rest and eccentric exercised groups. Eccentric exercise groups were further divided as rats killed after 1 hour and 48 hours of eccentric exercise. Estrogen (10 mg/kg) was administered subcutaneously for 30 days. Eccentric exercise was applied as treadmill run (15° downhill, 20 m/min) consisting of periods of "5 min" run and 2 min rest repeated 18 times. The rat liver was examined biochemically and histologically. Activities of GST, GSH-Px, CAT, SOD and MDA concentration were also measured spectrophotometrically. RESULTS: Some disruptions were detected in experimental groups compared with the control group. Additionally, exercise training caused an increase in SOD and decrease in GSH-Px activities in some experimental groups. SOD activities increased significantly in group 3 (Estrogen (-), eccentric exercise (+) killed (after 1 h), compared with group 5 (Estrogen (-), eccentric exercise (+) killed (after 48 h). On the other hand, GSH-Px activities were also significantly decreased in groups 3, 4 and 5 compared with the control group. Leukocyte infiltration in liver increased after 48 hours compared with after 1 hour and estrogen supplementation was not able to prevent this infiltration. CONCLUSIONS: Estrogen seemed to be not very effective to prevent eccentric exercise-induced liver damage.

Treatment with α-lipoic acid enhances the bone healing after femoral fracture model of rats.

This study investigated the fracture-healing effects of α-lipoic acid (α-LA), which was applied orally once daily in preventive treatment mode during 1 month after fracture induction. Rats were randomly divided into sham-operated group (group 1), femoral fracture control (group 2), femoral fracture + 25 mg/kg α-LA (group 3), and femoral fracture + 50 mg/kg α-LA (group 4). Rats in the experimental groups were orally administered 25 or 50 mg/kg α-LA once daily for 30 days starting from postoperative day 1. Thirty days postoperatively, the rats underwent X-ray imaging and were then euthanized for blood and tissue collection. Histopathological, biochemical, molecular, computed tomography (CT), and mechanical strength tests were performed on samples. The serum levels of osteocalcin (OC), osteopontin (OP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) did not differ significantly between groups 2 and 3. Serum OC, OP, TNF-α, and IL-6 levels in group 4 were significantly lower than those in group 3. From X-ray images, staging for fracture healing was scored as <2 in group 2, >2 in group 3, and >3 in group 4. In group 2, the average score of less than 2 suggests insufficient fracture healing; those of both the α-LA groups were >2, indicating progression of healing. Transforming growth factor beta (TGF-ß) messenger RNA (mRNA) levels were significantly higher in the sham group than in the femoral fracture control. Both doses of α-LA increased TGF-ß mRNA expression compared to the fracture group. CT results and biomechanical testing at 4 week after fracture demonstrated that α-LA has fastened bone healing, which was confirmed by stereological analyses in which 50 mg/kg α-LA increased the number of osteoclasts. Our findings indicate that α-LA supplementation promotes healing of femoral fractures in rats.

Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study.

Diabetes mellitus (DM) is one of the most common and chronic diseases, especially in post-menopausal periods. Neuro-degeneration occurs more frequently in post-menopausal diabetics. Therefore, we investigated ovariectomized rats cerebellar cortex response to the estradiol deficiency and hyperglycemia. For the ovariectomy, the rats were bilaterally ovariectomized, and then DM induced by a single dose of Alloxan monohydrate injection in ovariectomy or/and diabetic groups. During light and electron microscopic examination, degenerated Purkinje cells membrane, swollen organelles, degenerated mitochondria, edema formation and vacuolization were seen in the ovariectomy and ovariectomy-diabetic groups sections. In addition, increased apoptotic activity was observed in the ovariectomy and ovariectomy-diabetic groups compared to the control group. We demonstrated that estradiol and insulin deficiency can affect the cerebellar cortex, which support the hypothesis that the execution of neuronal damages in post-menopausal diabetics. Also, diabetes and menopause are major risks factors for many disorders including nervous system and the number of post-menopausal-diabetics are increasing world-wide.