The impact of apelin-13 on cisplatin-induced endocrine pancreas damage in rats: an in vivo study.

Apelin-13 is a peptide hormone that regulates pancreatic endocrine functions, and its benefits on the endocrine pancreas are of interest. This study aims to investigate the potential protective effects of apelin-13 in cisplatin-induced endocrine pancreatic damage. Twenty-four rats were divided into four groups: control, apelin-13, cisplatin, and cisplatin + apelin-13. Caspase-3, TUNEL, and Ki-67 immunohistochemical staining were used as markers of apoptosis and mitosis. NF-κB/p65 and TNFα were used to show inflammation. ß-cells and α-cells were also evaluated with insulin and glucagon staining in the microscopic examination. Pancreatic tissue was subjected to biochemical analyses of glutathione (GSH) and malondialdehyde (MDA). Apelin-13 ameliorated cisplatin-induced damage in the islets of Langerhans. The immunopositivity of apelin-13 on ß-cells and α-cells was found to be increased compared to the cisplatin group (p = 0.001, p = 0.001). Mitosis and apoptosis were significantly higher in the cisplatin group (p = 0.001). Apelin-13 reduced TNFα, NF-κB/p65 positivity, and apoptosis caused by cisplatin (p = 0.001, p = 0.001, p = 0.001). While cisplatin caused a significant increase in MDA levels (p = 0.001), apelin caused a significant decrease in MDA levels (p = 0.001). The results demonstrated a significant decrease in pancreatic tissue GSH levels following cisplatin treatment (p = 0.001). Nevertheless, apelin-13 significantly enhanced cisplatin-induced GSH reduction (p = 0.001). On the other hand, the serum glucose level, which was measured as 18.7 ± 2.5 mmol/L in the cisplatin group, decreased to 13.8 ± 0.7 mmol/L in the cisplatin + apelin-13 group (p = 0.001). The study shows that apelin-13 ameliorated cisplatin-induced endocrine pancreas damage by reducing oxidative stress and preventing apoptosis.

Preventive effects of melatonin on periodontal tissue destruction due to psychological stress in rats with experimentally induced periodontitis.

OBJECTIVE AND BACKGROUND: Psychological stress is a potential modifiable environmental risk factor causally related to the exacerbation of periodontitis and other chronic inflammatory diseases. This animal study aimed to investigate comprehensively the preventive efficacy of systemic melatonin administration on the possible effects of restraint stress on the periodontal structures of rats with periodontitis. METHODS: Forty-eight male Sprague Dawley rats were randomly divided into six groups: control, restraint stress (S), S-melatonin (S-Mel), experimental periodontitis (Ep), S-Ep, and S-Ep-Mel. Periodontitis was induced by placing a 3.0 silk suture in a sub-paramarginal position around the cervix of the right and left lower first molars of the rats and keeping the suture in place for 5 weeks. Restraint stress was applied simultaneously by ligation. Melatonin and carriers were administered to the control, S, Ep, and S-Ep groups intraperitoneally (10 mg/body weight/day, 14 days) starting on day 21 following ligation and subjection to restraint stress. An open field test was performed on all groups on day 35 of the study. Periodontal bone loss was measured via histological sections. Histomorphometric and immunohistochemical (RANKL and OPG) evaluations were performed on right mandibular tissue samples and biochemical (TOS (total oxidant status), TAS (total antioxidant status), OSI (oxidative stress index), IL-1ß, IL-10, and IL-1ß/IL-10) evaluations were performed on left mandibular tissue samples. RESULTS: Melatonin significantly limited serum corticosterone elevation related to restraint stress (p < .05). Restraint stress aggravated alveolar bone loss in rats with periodontitis, while systemic melatonin administration significantly reduced stress-related periodontal bone loss. According to the biochemical analyses, melatonin significantly lowered IL-1ß/IL-10, OSI (TOS/TAS), and RANKL/OPG rates, which were significantly elevated in the S-Ep group. CONCLUSION: Melatonin can significantly prevent the limited destructive effects of stress on periodontal tissues by suppressing RANKL-related osteoclastogenesis and oxidative stress.

Investigation of symptoms and lung functions in tea packaging factory employees.

Inhalation of organic powders may lead to various diseases such as asthma-like syndrome and hypersensitivity pneumonia. The study aim to evaluate respiratory health effects by respiratory function measurements, respiratory survey, ambient dust concentration, and toxic gas in workers of a tea packaging factory. 69 employees from different departments of the tea packaging factory were included. A group of 53 office workers of a separate establishment was included as a control. Sputum production in the morning was significantly higher in the tea packaging workers (p=0.013). Among the respiratory function values, only FEV1/FVC was lower in this group than in the control group. There was a significant decrease in FEF75% value among smokers in the study group compared to non-smokers. Respiratory effects observed in some food processing industry workers are also seen in the tea packaging industry. Effective dust control will positively affect the health of the workers. More studies are needed to better identify potential risks.

Agomelatine on cisplatin-induced nephrotoxicity via oxidative stress and apoptosis.

Drug-induced nephrotoxicity is the greatest deterrent to the use of cisplatin, which is a frequently used chemotherapeutic with proven effectiveness in cancer therapy. Agomelatine, which is used in the treatment of sleep disorders and depression, has gained attention in recent years with its antioxidative and anti-inflammatory effects. In this study, the effects of the synthetic melatonin agonist agomelatine on nephrotoxicity were investigated in a rat model of cisplatin-induced nephrotoxicity using biochemical, histological, and immunohistochemical methods. Thirty-two male rats were divided into 4 groups: 1. control group, 2. agomelatine group, 3. cisplatin group, 4. cisplatin + agomelatine group. In the cisplatin group, there were widespread atypical glomerular structures and vacuolization in tubular epithelial cells, necrotic tubules, deterioration of brush border structure in proximal tubules, and fibrotic areas characterized by diffuse polymorphonuclear leukocyte (PNL) and extensive collagen deposition in the interstitial spaces. However, in the cisplatin + agomelatine group, we observed a reduction in glomeruli of atypical structure and necrotic tubules, in PNL infiltration in interstitial spaces, and fibrotic areas compared to the cisplatin group. The cisplatin + agomelatine group showed lower malondialdehyde (MDA) serum creatinine, serum urea levels, and higher glutathione (GSH) levels compared to the cisplatin group. Immunohistochemical analyses revealed that the elevated NF-kß/p65, 8-OHdG, and cleaved caspase-3 positivity in the cisplatin group had significantly decreased in the cisplatin + agomelatine group. In conclusion, agomelatine showed a nephroprotective effect against cisplatin-induced nephrotoxicity.

Agomelatine attenuates cisplatin-induced cognitive impairment via modulation of BDNF/TrkB signaling in rat hippocampus.

Cisplatin is a drug used effectively in the treatment of malignant tumors. However, cisplatin has many side effects, including cognitive impairment. Agomelatine, a synthetic melatonin analogue, is an important antidepressant. Increasing evidence has shown that agomelatine may be a potential neuroprotective agent. The aim of this study was to investigate the effect of agomelatine on learning and memory functions in cisplatin-induced cognitive impairment in a rat model. Male rats were administered agomelatine and cisplatin for 4 weeks. Neurobehavioral tests were performed at the end of the 4th week. After behavioral tests, rats were euthanized and BDNF, TNF, IL-1ß, MDA and GSH levels were measured in hippocampal homegenates by ELISA. In addition, nNOS and TrkB receptor activity were measured immunohistochemically. The results showed that agomelatine significantly improved cognitive functions in spatial memory tests in rats with cisplatin-induced cognitive impairment. In addition, agomelatine treatment positively affected the discrimination index (DI). On the other hand, agomelatine treatment elevated cisplatin-suppressed hippocampal BDNF levels. Agomelatine treatment reduced cisplatin-induced neuroinflammation by suppressing TNF and IL-1ß levels. Similarly, agomelatine reduced oxidative stress in the hippocampus. Histological findings showed that agomelatine treatment reduced pyramidal neuron damage in hippocampal DG, CA1 and CA3. Cisplatin increased nNOS and TrkB positivity in DG, CA1 and CA3 neurons compared to control. In contrast, agomelatine treatment decreased both nNOS and TrkB positive scores. These findings indicate that agomelatine reduces cisplatin-related cognitive impairment by exerting anti-inflammatory action and possibly by the modulation of the BDNF/TrkB/nNOS pathways in the hippocampus.

The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment.

OBJECTIVE: Alzheimer's disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide. Novel therapeutic agents therefore need to be discovered in addition to traditional medications. Nimodipine appears to possess the potential to reverse cognitive impairment-induced dysfunction in learning and memory through its regulatory effect on the brain-derived neurotrophic factor (BDNF), acetylcholine (Ach), and acetylcholinesterase (AChE) pathway in the hippocampus and prefrontal cortex. METHODS: Twenty-four male Sprague Dawley rats weighing 380 ± 10 g were used for behavioral and biochemical analyses. These were randomly and equally assigned into one of three groups. Group 1 received saline solution alone via the intraperitoneal (i.p) route, and Group 2 received 1 mg/kg/day i.p. scopolamine once a day for three weeks for induction of learning and memory impairments. In Group 3, 10 mg/kg/day nimodipine was prepared in tap water and administered orally every day for three weeks, followed after 30 min by 1 mg/kg/day scopolamine i.p. Behavior was evaluated using the Morris Water Maze test. BDNF, ACh, and AChE levels were determined using the ELISA test in line with the manufacturer's instructions. RESULTS: Nimodipine treatment significantly increased the time spent in the target quadrant and the number of entries into the target quadrant compared to the scopolamine group alone. Additionally, BDNF and ACh levels in the hippocampus and prefrontal cortex decreased following 20-day scopolamine administration, while AChE activation increased. CONCLUSION: Nimodipine exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration in the hippocampus and prefrontal cortex.

The effects of apelin-13 against cisplatin-induced nephrotoxicity in rats.

Acute kidney injury (AKI) is observed in nearly 60% of patients undergoing cisplatin (CP) therapy. The aim of this study was to reveal the potential effects of apelin-13 (AP-13) in the prevention of CP-induced renal toxicity, together with its antioxidant and anti-inflammatory effect mechanisms. Four experimental groups were established. Group 1, the control group, received 0.9% saline solution alone intraperitoneally (IP). Group 2, the CP group, received CP IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 3, the CP + Apelin-13 (AP-13) group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free saline before injection every day for four weeks and administered IP. CP was administered IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 4, the AP-13 group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free 0.9% saline before injection every day for four weeks and administered IP. Thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin-1 beta, cleaved caspase-3, 8-hydroxy 2-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κß/p65) levels were then measured. Increased oxidative stress, inflammation, and apoptosis as a result of CP application activated the cascade. However, AP-13 administration reduced the oxidative stress increased by CIS with the determined antioxidant effect and reduced the damage by increasing total -SH levels. 8-OHdG and NF-κß/p65, which were up-regulated by triggering oxidative stress and inflammation, were down-regulated through the antioxidant and anti-inflammatory effects of AP-13.

Bee pollen increases hippocampal brain-derived neurotrophic factor and suppresses neuroinflammation in adult rats with chronic immobilization stress.

Chronic stress is a potential problem associated with anxiety, depression, and cognitive dysfunction. Bee pollen, a powerful antioxidant, has many therapeutic effects. In this study, we aimed to examine the effects of one of the Anatolian bee pollens on depression/anxiety. 24 male Sprague Dawley rats were divided into 3 groups as control, stress, and bee pollen + stress. Bee pollen (200 mg/kg/day) was given to rats exposed to physical stress for 10 days. Open field test (OFT) and forced swimming test (FST) were applied to monitor the behavioral changes of the rats. After behavioral tests, the rats were euthanized. Brain-derived neurotrophic factor (BDNF), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) levels were measured by ELISA to evaluate neurological and biochemical changes in rat hippocampal tissue. In addition, malondialdehyde (MDA) and glutathione (GSH) levels in the brain were evaluated. According to the behavioral test results, bee pollen reduced anxiety-like behavior but did not affect depression-like behavior. We also found that bee pollen suppressed neuroinflammation while reducing oxidative stress and lipid peroxidation in hippocampal tissues. Moreover, bee pollen significantly increased the level of BDNF in the hippocampus. In conclusion, bee pollen reduced oxidative damage and neuroinflammation caused by immobilization stress in rat brain tissue. Therefore, we suggest that bee pollen may be an effective natural compound in alleviating the negative effects caused by immobilization stress.

Effect of white tea consumption on serum leptin, TNF-α and UCP1 gene expression in ovariectomized rats.

BACKGROUND: Obesity and dyslipidemia due to estrogen deficiency are among the important health problems in menopausal women. Increasing evidence reports the anti-obesity and anti-hyperlipidemic properties of tea polyphenols. However, the effect of white tea (WT) with high polyphenol content on overweight and lipid profile is uncertain. Here, we aimed to examine the effects of long-term WT consumption on serum leptin, tumor necrosis factor- alpha (TNF-α) and uncoupling protein 1 (UCP1) mRNA gene expression in ovariectomized (OVX) rats. METHODS: Adult rats were divided into four groups (n = 8): (i) sham, (ii) OVX, (iii) WT and (iv) OVX + WT. WT was given at a dose of 0.5% w/v for 12 weeks. In the study, body weight, serum leptin, TNF, estradiol (E2) levels, lipid profile and UCP1 mRNA gene expression in brown adipose tissue (BAT) were evaluated. RESULTS: There was a significant increase in body weight of OVX rats, which was decreased following WT consumption. While leptin and E2 levels decreased in the OVX group, TNF levels increased. There was no difference between the NF-kB levels of the groups. In addition, BAT UCP1 mRNA expression was significantly decreased in OVX groups, while WT treatment stimulated UCP1 activity. CONCLUSION: We explain the stimulatory effect of WT on weight loss mainly by the induction of UCP1 gene-mediated thermogenesis and suppression of inflammation. Therefore, we suggest that prolonged WT consumption may have beneficial effects in limiting excess weight gain caused by estrogen deficiency.

Can Dexmedetomidine Be Effective in the Protection of Radiotherapy-Induced Brain Damage in the Rat?

Approximately 7 million people are reported to be undergoing radiotherapy (RT) at any one time in the world. However, it is still not possible to prevent damage to secondary organs that are off-target. This study, therefore, investigated the potential adverse effects of RT on the brain, using cognitive, histopathological, and biochemical methods, and the counteractive effect of the α2-adrenergic receptor agonist dexmedetomidine. Thirty-two male Sprague Dawley rats aged 5-6 months were randomly allocated into four groups: untreated control, and RT, RT + dexmedetomidine-100, and RT + dexmedetomidine-200-treated groups. The passive avoidance test was applied to all groups. The RT groups received total body X-ray irradiation as a single dose of 8 Gy. The rats were sacrificed 24 h after X-ray irradiation, and following the application of the passive avoidance test. The brain tissues were subjected to histological and biochemical evaluation. No statistically significant difference was found between the control and RT groups in terms of passive avoidance outcomes and 8-hydroxy-2'- deoxyguanosine (8-OHdG) positivity. In contrast, a significant increase in tissue MDA and GSH levels and positivity for TUNEL, TNF-α, and nNOS was observed between the control and the irradiation groups (p < 0.05). A significant decrease in these values was observed in the groups receiving dexmedetomidine. Compared with the control group, gradual elevation was determined in GSH levels in the RT group, followed by the RT + dexmedetomidine-100 and RT + dexmedetomidine-200 groups. Dexmedetomidine may be beneficial in countering the adverse effects of RT in the cerebral and hippocampal regions.

Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction.

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. The aim of this study was to investigate the role of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway and the potential inhibitory effects of apelin-13 in the mechanism of cisplatin-induced hippocampal damage and cognitive impairment. Apelin-13 was administered to adult sprague dawley male rats at a dose of 20 nmol/kg every day for 4 weeks, cisplatin was administered at a dose of 5 mg/kg once a week for 4 weeks. The spatial and recognition memory tests of the rats were performed on the 5th week. BDNF and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were measured by ELISA in hippocampal homogenates. Pyramidal neuron and glial cell damage in the hippocampal CA1, CA3 and dentate gyrus (DG) were analyzed histologically. TrkB activity in the hippocampus was determined by immunohistochemical methods. Cisplatin impaired spatial and recognition memory in rats, while apelin-13 improved spatial memory but did not affect recognition memory. Cisplatin suppressed BDNF in the hippocampus while increased IL-1ß and TNF-α. In contrast, apelin-13 administration increased BDNF but significantly suppressed TNF-α and IL-1B. Cisplatin caused pyramidal neuron and glial cell damage in CA1, CA3 and DG. In the cisplatin + apelin-13 group, however, pyramidal neuron and glial cell damage was less than those without apelin-13. Cisplatin increased TrkB activity in the hippocampus, which was counteracted by apelin-13. In conclusion, apelin-13 reduced the cisplatin-induced cognitive deficiency, by suppressing inflammation and stimulating the synthesis and activation of neurotrophic factors in hippocampal tissue.

White Tea Reduced Bone Loss by Suppressing the TRAP/CTX Pathway in Ovariectomy-Induced Osteoporosis Model Rats.

Osteoporosis is an important skeletal disease characterized by bone weakness and high risk of fracture in postmenopausal women. Tea consumption is known to play an important role in the prevention or alleviation of osteoporosis. However, the therapeutic effects of aqueous extracts of white tea (WT) have not been evaluated in osteoporosis rat models. The aim of this study was to investigate the potential anti-osteoporotic role of WT in ovariectomized (OVX) rats. WT was given orally at 0.5% w/v doses for 12 weeks in OVX rats. Biochemical parameters in blood samples, bone tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type 1 collagen (CTX) and estradiol levels were evaluated. Bone mineral density and bone mineral content values were measured in the left femur. In addition to histopathological examination, osteolcalcin, osteopontin and TUNEL levels were determined. OVX group data demonstrated that bone loss occurred by thinning of the metaphyseal growth plates of the femur. Similarly, the levels of TRAP and CTX, markers of osteoclastic activity, were found to be high concurrently with a decrease in femoral bone mineral density. In addition, increased osteolcalcin and osteopontin levels were present in the metaphyseal growth zones. On the other hand, while TRAP and CTX levels were suppressed in the OVX-WT group, bone mineral content increased. In ad-dition, TUNEL, osteocalcin and osteopontin positivity decreased in the right femoral metaphysis growth zones, proliferating zone and resting zone cells. These results showed that chronic WT consumption has a protective effect by reducing bone resorption in OVX-induced osteoporotic rats.

The effect of bee pollen on reproductive and biochemical parameters in methotrexate-induced testicular damage in adult rats.

OBJECTIVES: Methotrexate (MTX) is an anticancer drug used in chemotherapy. MTX was known for its toxic effects involving most of the organs including testis. Bee pollen is healthy food for human and has antioxidant effect. We intended to determine protective effect of bee pollen against testicular injury caused by MTX in rats. METHODS: Thirty-two adult Sprague Dawley male rats were used, and 4 groups were formed: control, MTX, pollen, and MTX + pollen. Rats were given pollen at a dose of 400 mg/kg with intragastric gavage for 10 days. On day 7, MTX was administered a single dose of 30 mg/kg ip. Serum testosterone and LH, tissue MDA level, and SOD and CAT enzyme activities were examined. In addition, spermatological parameters were evaluated. RESULTS: MDA level and SOD activity increased while testosterone level decreased significantly in the MTX group compared to the control group. In the MTX + pollen group, MDA level and SOD activity decreased while testosterone level increased. There was no significant change in CAT activity and LH values. Abnormal sperm ratio decreased in the MTX + pollen group compared to the MTX group. CONCLUSIONS: Our results suggest that bee pollen has a healing effect on reproductive parameters in testicular damage caused by MTX.

The effect of white tea on serum TNF-α/NF-κB and immunohistochemical parameters in cisplatin-related renal dysfunction in female rats.

OBJECTIVE: Nephrotoxicity is the most important side effect of the antineoplastic drug cisplatin, thereby restricting its use. The aim of this study was to investigate the protective effects of white tea infusions (WT) against renal damage induced by cisplatin (CP) in rats by biochemical and histopathological means. MATERIALS AND METHODS: This study used 24 female Sprague Dawley rats at 12-14 weeks of age and weighing 250-300 g. Rats were divided into three groups: Control, CP and CP + WT groups. CP was injected 7 mg/kg i.p as a single dose/rat in the CP group. White tea was given at a dose of 0.5% (w/v) for 4 weeks. At the end of the experiment, blood urea nitrogen (BUN), creatinine, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) along with caspase-3 in the kidney were evaluated in study. RESULTS: BUN, creatinine, TNF-α, NF-κB and IL-6 levels of the CP group showed a statisically significant increase in comparison to the control group. TNF-α, NF-κB and IL-6 levels showed a statistically significant decrease in the CP + WT group with respect to the CP group. Caspase-3 levels in tubular epithelial cells decreased in CP + WT group compared with CP group (p = 0.02). CONCLUSION: White tea infusions reduced significantly the nephrotoxicity of CP. The anti-nephrotoxic feature of the infusion may be attributed primarily to its anti-inflammatory and anti-apoptotic characteristics.

The Effects of Hesperidin and Quercetin on Serum Tumor Necrosis Factor-Alpha and Interleukin-6 Levels in Streptozotocin-induced Diabetes Model.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder that occurs as a result of absolute or relative insufficiency of insulin release and/or insulin effect due to impairment of carbohydrate, fat and protein metabolism, and it is characterized by hyperglycemia and leads to various complications. OBJECTIVE: In this study, it was aimed to investigate the effects of hesperidin (HP) and quercetin, which are natural flavonoids, on serum malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels in rats with streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: Group 1 served as control rats (C); Group 2 served as diabetic rats (DM); Group 3 served as diabetic rats administered HP (DM + HP) (100 mg/kg b. w.); and Group 4 served as diabetic rats administered quercetin (DM + Q) (100 mg/kg b. w.). RESULTS: Serum MDA and GSH levels were significantly higher in STZ-induced DM group than control group (P < 0.05). In DM + HP and DM + Q groups, MDA levels were significantly decreased compared to DM groups (P < 0.05), but there was no significant difference GSH levels between DM, DM + HP, and DM + Q groups (P > 0.05). TNF-α levels in STZ-induced DM group were significantly decreased compared to control group (P < 0.05), and groups of DM + HP and DM + Q had higher serum TNF-α levels than STZ-induced DM group (P < 0.05). In STZ-induced DM group, serum IL-6 levels were decreased compared to control group (P < 0.05). CONCLUSION: As a result, in this study, we determined that HP and quercetin may play an effective role in regulating insulin metabolism metabolism in diabetes. However, considering the incompatibility of various results in the literature as well as our own results, we think that the actual role of cytokines in the pathogenesis of diabetes is one of the issues that need to be clarified in further studies. SUMMARY: Hesperidin (HP) and quercetin reduced the insulin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and malondialdehyde (MDA) serum levels and raised the glutathione (GSH) levels compared to diabetes mellitus (DM) groupSZT-induced DM increased the MDA serum levels and decreased the GSH levels compared to control groupHP and quercetin-treated rats showed higher interleukin-6 and tumor necrosis factor alpha cytokine levels than DM groupHP and quercetin may play an effective role in regulating insulin metabolism in diabetes. Abbreviations used: DM: Diabetes mellitus, MDA: Malondialdehyde, GSH: Glutathione; IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, HP: Hesperidin, Q; Quercetin, STZ: Streptozotocin, TC: Total cholesterol, TG: Triglyceride, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, VLDL-C: Very-low-density lipoprotein cholesterol.

The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model.

OBJECTIVE: The aim of this study is to investigate the roles of SIRT1 and NF-κB in the pathogenesis of diabetes mellitus in rats with STZ-induced diabetes and determine the effects of hesperidin and quercetin on oxidative stress and on the levels of SIRT1 and NF-κB. MATERIALS AND METHODS: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: group 1 served as control rats (C); group 2 served as diabetic rats (DM); group 3 served as diabetic rats administered hesperidin (DM+HSP) (100mg/kg b.w.) in aqueous suspension orally for 15 days; and group 4 served as diabetic rats administered quercetin (DM+Q) (100mg/kg b.w.) in aqueous suspension orally for 15 days. RESULTS: In diabetic group, liver and kidney SIRT1, SOD and CAT activities were significantly lower than control group (p<0.05). Hesperidin and quercetin caused significant increase in the SIRT1, SOD and CAT activities of both DM+HP and DM+Q groups kidney tissues compared to DM group (p<0.05). Liver SOD activies were not found to differ significantly between DM, DM+Q and DM+HP groups (p>0.05). In DM+HP group, liver CAT activities were significantly higher than DM (p<0.05), but there was no significant difference in liver CAT activities between DM and DM+Q (p>0.05). In diabetic group, liver and kidney NF-κB and MDA levels were increased compared to control group (p<0.05), and groups of DM+HP and DM+Q had lower NF-κB and MDA levels than diabetic group (p<0.05). CONCLUSION: As a conclusion, based on the results we obtained from this study and the literature data discussed above, we determined in STZ-induced diabetic rats that, increased glucose levels and liver and kidney damage markers decreased significantly after administration of hesperedin and quercetin, and that oxidative stress and NF-κB levels increased while SIRT1 levels decreased in the diabetic group.

Effects of apelin-13 in mice model of experimental pain and peripheral nociceptive signaling in rat sensory neurons.

OBJECTIVE: Apelin-13 is an endogenous peptide with potential analgesic action, although the sites of its analgesic effects remain uncertain and the results are even controversial with regard to its pain modulating action. This study evaluated the possible pain-modulating action of peripherally administered apelin-13 using heat-induced, withdrawal latency to the thermal stimuli, acute pain model in mice. Involvement of peripheral mechanisms was tested, by using the intracellular calcium concentrations as a key signal for nociceptive transmission, in cultured rat dorsal root ganglion (DRG) neurons. METHODS: DRG neurons were cultured on glass coverslips following enzymatic digestion and mechanical agitation, and loaded with the calcium-sensitive dye Fura-2 acetoxymethyl ester (1 µM). Intracellular calcium responses in individual DRG neurons were quantified by ratiometric calcium imaging technique. RESULTS: Peripheral injection of a single dose of apelin-13 (100 mg/kg and 300 mg/kg) significantly decreases the latency to painful stimuli in a dose and time-dependent manner (p < 0.01, p < 0.05, respectively, n = 8 each). Apelin-13 (0.1 µM and 1 µM) did not produce a significant effect on cytoplasmic Ca(2+) ([Ca(2+)](i)) responses, evoked by membrane depolarization, in cultured rat DRG neurons. CONCLUSION: Together these results indicate that apelin-13 can cause increased pain sensitivity after peripheral administration, but this effect does not involve calcium mediated signaling in primary sensory neurons.