Cellular localisation of the kinin B1R in the pancreas of streptozotocin-treated rat and the anti-diabetic effect of the antagonist SSR240612

Abstract The mechanism by which kinin B1 receptor (B1R) contributes to type 1 diabetes is addressed by determining the impact of its inhibition on diabetes and on its pancreatic expression and cellular localisation on immunocompetent cells and primary sensory C-fibres. Rats were made diabetic with streptozotocin (STZ). On day 4, they were treated daily for 7 days with a B1R antagonist (SSR240612, 10 mg/kg) or its vehicle. The surviving β-cells were measured by immunostaining. The expression of B1R, iNOS, TNF-α, macrophages, TCD4+, CGRP and TRPV1 was measured by Western blotting, qRT-PCR and immunofluorescence. Macrophages and TCD4+ lymphocytes were absent in control, but distributed abundantly in the pancreas of STZ-diabetic rats. B1R was upregulated on these immune cells infiltrating the diabetic rat pancreas while it was not expressed on primary sensory C-fibres even if the expression of TRPV1 and CGRP was enhanced. SSR240612 prevented the infiltration of macrophages and TCD4+ lymphocytes and the upregulation of B1R, iNOS, TNF-α and TRPV1. SSR240612 corrected hyperglycaemia and hypoinsulinaemia by improving the Langerhans islets survival or regeneration. It is concluded that kinin B1R antagonism exerts anti-diabetic action by preventing the infiltration of immune cells in the pancreas and by preserving the integrity of Langerhans islets β-cells.

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Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat: autoradiographic and functional evidence

British Journal of Pharmacology ◽

10.1038/sj.bjp.0704999 ◽

2003 ◽

Vol 138 (1) ◽

pp. 13-22 ◽

Cited By ~ 26

Author(s):

Rose Mari J Vianna ◽

Brice Ongali ◽

Domenico Regoli ◽

João Batista Calixto ◽

Réjean Couture

Keyword(s):

Diabetic Rat ◽

B1 Receptor ◽

Kinin B1 Receptor ◽

Streptozotocin Diabetic Rat

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Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

The Scientific World JOURNAL ◽

10.1155/2014/908098 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 8

Author(s):

Mazen M. Jamil Al-Obaidi ◽

Fouad Hussain Al-Bayaty ◽

Rami Al Batran ◽

Jamal Hussaini ◽

Goot Heah Khor

Keyword(s):

Normal Saline ◽

Ellagic Acid ◽

Tooth Extraction ◽

Healing Process ◽

Diabetic Rats ◽

Male Rats ◽

Diabetic Rat ◽

Control Group ◽

Tooth Socket ◽

The Impact

Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.Methods. Twenty-fourSprague Dawleymale rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test.Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat.Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction.

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Ocular Application of the Kinin B1 Receptor Antagonist LF22-0542 Inhibits Retinal Inflammation and Oxidative Stress in Streptozotocin-Diabetic Rats

PLoS ONE ◽

10.1371/journal.pone.0033864 ◽

2012 ◽

Vol 7 (3) ◽

pp. e33864 ◽

Cited By ~ 41

Author(s):

Mylène Pouliot ◽

Sébastien Talbot ◽

Jacques Sénécal ◽

Florence Dotigny ◽

Elvire Vaucher ◽

...

Keyword(s):

Oxidative Stress ◽

Receptor Antagonist ◽

Diabetic Rats ◽

B1 Receptor ◽

Kinin B1 Receptor ◽

Streptozotocin Diabetic Rats ◽

Retinal Inflammation ◽

And Oxidative Stress

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Reciprocal Regulatory Interaction between TRPV1 and Kinin B1 Receptor in a Rat Neuropathic Pain Model

International Journal of Molecular Sciences ◽

10.3390/ijms21030821 ◽

2020 ◽

Vol 21 (3) ◽

pp. 821 ◽

Cited By ~ 1

Author(s):

Veronica Cernit ◽

Jacques Sénécal ◽

Rahmeh Othman ◽

Réjean Couture

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Mrna Expression ◽

Thermal Hyperalgesia ◽

Mrna Levels ◽

Regulatory Interaction ◽

B1 Receptor ◽

Tnf Α ◽

Kinin B1 Receptor ◽

Sensory Fibers

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg−1, i.p.) or TRPV1 (SB366791, 1 mg·kg−1, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP.

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Glucose and Lipid Lowering Potentials of Heliotropium indicum L. Leaves in Alloxan-Induced Hyperglycaemic Rats

Notulae Scientia Biologicae ◽

10.15835/nsb849850 ◽

2016 ◽

Vol 8 (4) ◽

pp. 414-421 ◽

Cited By ~ 2

Author(s):

Rasheed Bolaji IBRAHIM ◽

Jubril Olayinka AKOLADE ◽

Raliat Abimbola ALADODO ◽

Omoaruemike Ebele OKEREKE ◽

Sarah Abimbola AKANDE

Keyword(s):

Fasting Blood Glucose ◽

Clinical Importance ◽

Hdl Cholesterol ◽

Diabetic Rats ◽

Lipid Lowering ◽

Diabetic Rat ◽

Hepatic Glycogen ◽

Β Cells ◽

Aqueous Leaf Extract ◽

Heliotropium Indicum

The antidiabetic potentials of Heliotropium indicum L. leaf aqueous (HILA) extract used for the management of diabetes by Traditional Medicinal Practitioners (TMPs) in Nigeria was assessed. Alloxan (ALX)-induced hyperglycaemic rats were orally administered with known folkloric dosage of 30 and 75 mg/kg b. wt. of HILA extract, once a day, for 14 days. Fasting blood glucose (FBG) levels were monitored and pancreatic histology was examined. Net hepatic glycogen (GLY) concentration and lipid profiles were also determined. Prior to treatment, ALX-induced hyperglycaemia (>250 mg/dL) was established in rats. Oral administration of 30 and 75 mg/kg b. wt. HILA extract to diabetic rats for 14 days caused significant reduction in FBG to baseline values observed in non-diabetic conditions. Treatment with HILA extract also showed improvement in lipid abnormalities observed in hyperglycaemic condition, levels of triglyceride, total cholesterol and LDL-cholesterol were significantly reduced and HDL-cholesterol increased resulting in improved artherogenic index. Hepatic GLY concentration was significantly increased in diabetic rat treated with the extract. Histological examinations showed degenerated and sparse pancreatic islets β-cells in non-treated diabetic rat, whereas microscopy of treated rats showed mild to normal architecture with enriched β-cells. Preliminary phytochemical profiling of the extract revealed the presence of alkaloids (2.54 mg/g), saponins (0.28 mg/g), phenols (0.04 mg/g) and anthraquinones (0.01 mg/g). Results from this study revealed that the aqueous leaf extract of H. indicum possesses not only antihyperglycaemic, but also antidyslipidemic activities, that may prove to be of clinical importance in the management of diabetes and associated secondary complications.

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Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes

BioMed Research International ◽

10.1155/2015/153573 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 48

Author(s):

Mohamed Afifi ◽

Omar A. Almaghrabi ◽

Naif Mohammed Kadasa

Keyword(s):

Zinc Oxide ◽

Mrna Expression ◽

Zinc Oxide Nanoparticles ◽

Sperm Count ◽

Testicular Tissue ◽

Diabetic Rats ◽

Diabetic Rat ◽

Oxide Nanoparticles ◽

Sperm Characteristics ◽

The Impact

The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats.

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Role of the Kinin B1 Receptor (B1R) in Diabetic Rats exposed to Septic Shock

Canadian Journal of Diabetes ◽

10.1016/s1499-2671(08)24135-3 ◽

2008 ◽

Vol 32 (4) ◽

pp. 333

Author(s):

Nejla Tidjane ◽

Réjean Couture

Keyword(s):

Septic Shock ◽

Diabetic Rats ◽

B1 Receptor ◽

Kinin B1 Receptor

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Immunological Changes in Peripheral Blood of Ankylosing Spondylitis Patients during Anti-TNF-α Therapy and Their Correlations with Treatment Outcomes

Journal of Immunology Research ◽

10.1155/2021/1017938 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Rongjuan Chen ◽

Hongyan Qian ◽

Xiaoqing Yuan ◽

Shiju Chen ◽

Yuan Liu ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Treatment Response ◽

Immune Cells ◽

Peripheral Blood ◽

Regulatory B Cell ◽

Follicular Helper ◽

Tnf Α ◽

The Difference ◽

Factor Α ◽

The Impact

Tumor necrosis factor-α (TNF-α) inhibitors are the main types of biological conventional synthetic disease-modifying antirheumatic drugs and have efficacy in treating ankylosing spondylitis (AS) which is not sensitive for nonsteroidal anti-inflammatory drug. However, the impact of TNF-α inhibitors on immune cells in patients with AS is still clearly undefined, and the impact of immune cells on treatment response is also largely elusive. This study is aimed at evaluating the longitudinal changes of circulating immune cells after anti-TNF-α therapy and their associations with treatment response in AS patients. Thirty-five AS patients receiving the treatment of anti-TNF-α therapy were included into this prospective observational study. The frequencies of immune cells including Th1, Th2, Th17, regulatory T cell (Treg), T follicular helper cell (Tfh), and regulatory B cell (Breg) in the peripheral blood were measured by flow cytometry at baseline and 4 time points after therapy. The difference in the circulating immune cells between responders and nonresponders was compared. This study suggested that anti-TNF-α therapy could significantly reduce circulating proinflammatory immune cells such as Th17 and Tfh, but significantly increased the percentages of circulating Treg and Breg. Moreover, circulating Breg may be a promising predictor of response to anti-TNF-α therapy in AS patients.

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Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6421 ◽

2020 ◽

Vol 40 (12) ◽

pp. 1077-1087

Author(s):

Marina G.P. Baptista ◽

Cintia G.M. Ferreira ◽

Yuri M.L. Albuquerque ◽

Carolline G. D’assunção ◽

Rebeca C. Alves ◽

...

Keyword(s):

Cerebral Cortex ◽

Frontal Cortex ◽

Intraperitoneal Administration ◽

Diabetic Rats ◽

Hypoglycemic Agents ◽

Albino Rats ◽

Tnf Α ◽

Frontal Cerebral Cortex ◽

The Impact ◽

The Brain

ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.

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