Adem Kara

Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg−1 body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4)

The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. CCl(4) challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl(4) group. Also, CD68(+) and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunopositive staining cells in the liver, but CD68(+) staining areas were significantly decreased in the PG+CCl(4) when compared to CCl(4) group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl(4)-induced liver damages in rats.

Pomegranate Seed Extract Attenuates Chemotherapy-Induced Acute Nephrotoxicity and Hepatotoxicity in Rats

Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.

Therapeutic Effects of Alpha Lipoic Acid and Vitamin C on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical, Histochemical, and Stereologic Study

BACKGROUND Alpha lipoic acid (ALA) and vitamin C (Vit-C) are very important and powerful antioxidants that have been used for the treatment of many diseases. The present study aims to investigate the role of ALA and Vit-C substances in the treatment of alveolar bone resorption in periodontal diseases. METHODS Thirty-six male Wistar albino rats were randomly divided into four groups as follows: 1) control rats; 2) rats with experimental periodontitis (PED); 3) rats with PED treated with ALA (ALA); and 4) rats with PED treated with ALA+Vit-C (ALA+Vit-C). PED was simulated by placing ligatures around the neck of teeth for 5 weeks. After ligature removal, the PED group was given a single intragastric dose of 1 mL saline, and the ALA and ALA+Vit-C groups were treated with an intragastric dose of 50 mg/kg ALA and ALA+Vit-C for 15 days, respectively. Levels of serum bone alkaline phosphatase (B-ALP) and myeloperoxidase (MPO) activity in gingival tissues were analyzed. To evaluate the osteoclast activation, expression of activated receptor activator nuclear factor-kappa B ligand (RANKL) and bone density index (BDI) were determined stereologically in the bone sections obtained from the mandibles of the rats. RESULTS The results showed statistically significant differences between the PED group and groups treated with antioxidant according to B-ALP, MPO, RANKL, and BDI values (P <0.05). ALA and ALA+Vit-C treatments showed beneficial effects on the mesial/distal periodontal bone support at the ligature-induced periodontitis tooth areas. CONCLUSION This study shows that ALA and Vit-C treatment provides therapeutic effects on inhibition of alveolar bone resorption and periodontal tissue destruction.

Effects of melatonin on islet neogenesis and beta cell apoptosis in streptozotocin-induced diabetic rats: an immunohistochemical study

This investigation was carried out to explore the antidiabetic, antiapoptotic and neogenetic effects of melatonin (MLT) in streptozotocin-induced diabetic rats. Sixty-four male rats were assigned randomly to one of four groups for periods of 21 and 42 d as follows; i) control, ii) MLT, iii) diabetic (DM), and iv) DM + MLT. Immunohistochemical methods were used -with pancreatic tissue to determine the intensity of insulin, caspase-3 and Bcl-x(L) immune reactivities, and new islet formation. In untreated DM rats, BW loss, increased plasma glucose and MLT concentrations, as well as cytoplasmic degranulation and vacuolization were observed. We also observed a marked increase in the number of apoptotic caspase-3 positive cells and a few insulin- positive cells, but not antiapoptotic Bcl-x(L) positive cells. Observations in the DM + MLT-treated group revealed a high intensity of insulin- and antiapoptotic Bcl-x(L) immune reactivities at 21 and 42 d. Moreover, data indicated that MLT may cause beta cell proliferation and that new small islets originate from cells associated with ductal epithelium and from centroacinar cells by day 21. These data indicate that; i) MLT treatment may stimulate neogenesis in the pancreas of diabetic rats, and ii) MLTs antiapoptotic action may increase beta cell differentiation and caspase-3 inactivation or Bcl-x(L) activation.

Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study

BACKGROUND The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats. METHODS Twenty-four male Sprague-Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel-Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel-Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b-ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor-kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group. RESULTS Melatonin treatment decreased serum CTX levels and increased b-ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel-Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel-Ped group compared to the Ped group (P <0.05). CONCLUSION This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.

Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis

BACKGROUND The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. METHODS Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. RESULTS Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups. CONCLUSION It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.

A Stereological Assessment Method for Estimating the Surface Area of Cycloids

OBJECTIVE In this study, we sought to determine differences in estimations of surface area made by classical vertical uniform random (VUR) section series and vertical section series obtained perpendicular to a fixed horizontal plane. MATERIALS AND METHODS One volunteer subject (male, 25 years of age) with no neurological deficit was chosen at random from a bank of controls in the magnetic resonance (MR) image data library of the Department of Radiology. First, a soccer ball with known geometrical features (radius: 9.75 cm) was imaged using a T1-weighted MR scanner at 5-mm thickness (total 40 sections) to test the validity and reliability of surface area and volume measurements obtained via stereological methods. Second, T1-weighted MR section profiles were obtained from a volunteer individual. Surface area and volume estimation procedures were carried out using the Stereo Investigator 6, MicroBright-Field, Inc., USA. CONCLUSIONS We determined that there are no differences in either surface area or volume estimations made using VUR sections and direct vertical sections. We have performed an exhaustive series analysis with a variety of objects.

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

Abstract 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.

Hepatic effects of ketamine administration for 2 weeks in rats

The aim of the present study was to investigate the long-term and high-dose application of ketamine on the liver by employing histologic and biochemical methods. A total of 30 male rats were randomly assigned to control and four treatment groups (n: 6). Saline for control group and different doses of ketamine for four treatment groups (40, 60, 80 and 100 mg kg−1) were administered intraperitoneal twice a day for 2 weeks. Immunohistological staining, light and electron microscopy were used to study tissue specimens. Histopathological changes were more severe and diverse in groups 80 and 100 mg kg−1 day−1, and the least significant change was observed in groups 40 and 60 mg kg−1 day−1. The most important ultrastructural changes were seen in mitochondria and in the rough endoplasmic reticulum. The immunoreactivity of calcineurin was determined as different. Prolonged use of ketamine caused hepatocellualar toxicity and histological changes in hepatocytes in a dose-dependent manner in all experimental groups.