Liraglutide treatment attenuates inflammation markers in the cardiac, cerebral and renal microvasculature in streptozotocin‐induced diabetic rats

Baylan, Umit; Korn, Amber; Emmens, Reindert W.; Schalkwijk, Casper G.; Niessen, Hans W.M.; Krijnen, Paul A J; Şimşek, Suat

doi:10.1111/eci.13807

Cited by 17 publications

(9 citation statements)

References 46 publications

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“…Liraglutide has been studied the most extensively. In STZ-induced diabetic rats, liraglutide decreased the levels of IL-1β, TNF-α, ICAM-1, and VCAM-1 in the ventricle [63,64]. In parallel, serum levels of IL-6 and IL-1β were decreased in liraglutidetreated diabetic non-human primates [65].…”

Section: Glp-1ramentioning

confidence: 86%

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Balogh

Wagner

Fekete

2023

IJMS

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Metabolic diseases, particularly diabetes mellitus (DM), are significant global public health concerns. Despite the widespread use of standard-of-care therapies, cardiovascular disease (CVD) remains the leading cause of death among diabetic patients. Early and evidence-based interventions to reduce CVD are urgently needed. Large clinical trials have recently shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) ameliorate adverse cardiorenal outcomes in patients with type 2 DM. These quite unexpected positive results represent a paradigm shift in type 2 DM management, from the sole importance of glycemic control to the simultaneous improvement of cardiovascular outcomes. Moreover, SGLT2i is also found to be cardio- and nephroprotective in non-diabetic patients. Several mechanisms, which may be potentially independent or at least separate from the reduction in blood glucose levels, have already been identified behind the beneficial effect of these drugs. However, there is still much to be understood regarding the exact pathomechanisms. This review provides an overview of the current literature and sheds light on the modes of action of novel antidiabetic drugs, focusing on inflammation, oxidative stress, and fibrosis.

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Section: Glp-1ramentioning

confidence: 86%

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Balogh

Wagner

Fekete

2023

IJMS

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“…High glucose induces oxidative stress on vessels can cause endothelial dysfunction (Tian et al, 2014;Goulopoulou et al, 2015;Kaur et al, 2022). In streptozotocin-induced-diabetic vessels of rats, the contractile response was greater as compared to control (Majithiya and Balaraman, 2005;Baylan et al, 2022). However, in another study with streptozotocininduced -diabetic rats, the vessels contractions were smaller in comparison to control (Lingbo et al, 2005).…”

Section: Discussionmentioning

confidence: 97%

Effect of sulfasalazine on endothelium-dependent vascular response by the activation of Nrf2 signalling pathway

Sonmez

Shahzadi²,

Kose³

et al. 2022

Front. Pharmacol.

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Background: Diabetes mellitus leads to endothelial dysfunction and accumulation of oxygen radicals. Sulfasalazine-induced Nrf2 activation reduces oxidative stress in vessels. Thus, in the present study, we investigated the effects of sulfasalazine on endothelial dysfunction induced by high glucose. We also ascribed the underlying mechanism involved in glucose-induced endothelial dysfunction.Methods: For this experiment we used 80 Wistar Albino rats thoracic aorta to calculate the dose response curve of noradrenaline and acetylcholine. Vessels were incubated in normal and high glucose for 2 h. To investigate glucose and sulfasalazine effects the vessels of the high glucose group were pre-treated with sulfasalazine (300 mM), JNK inhibitor (SP600125), and ERK inhibitor (U0126) for 30 min. The dose response curve was calculated through organ bath. The eNOS, TAS, TOS, and HO-1 levels were estimated by commercially available ELISA kits.Results: In the high glucose group, the Emax for contraction was significantly higher (p < 0.001), and Emax for relaxation was lower than that of control. These functional changes were parallel with the low levels of eNOS (p < 0.05). High glucose vessel treated with sulfasalazine showed low Emax value for contraction (p < 0.001) however, the Emax for relaxation was significantly high (p < 0.001) when compared to high glucose group. In the JNK group, Emax for contraction and relaxation was inhibited (p < 0.001) compared to sulfasalazine treated vessels. HO—1 enzyme levels were significantly low (p < 0.01) with sulfasalazine but higher with ERK inhibitor (p < 0.05).Conclusion: High glucose induced endothelial dysfunction and sulfasalazine reduced damage in high glucose vessels by activating eNOS, antioxidant effect through HO-1 enzymes and particularly inducing Nrf2 via the ERK and JNK pathways.

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“…Group I (control group) received vehicle distilled water (0.5 mL) per oral plus normal saline subcutaneously for 2 weeks followed by subcutaneous injection of normal saline only for 14 days. Group II (liraglutide group) received daily liraglutide subcutaneous injection (200 μg/kg body weight) dissolved in normal saline for 4 weeks 10,11 . Group III (valproic acid‐treated group) was administrated sodium valproate (500 mg/kg) dissolved in distilled water (0.5 mL) via oral gavage for 2 weeks 12 .…”

Section: Methodsmentioning

confidence: 99%

“…weight) dissolved in normal saline for 4 weeks. 10,11 Group III (valproic acid-treated group) was administrated sodium valproate (500 mg/kg) dissolved in distilled water (0.5 mL) via oral gavage for 2 weeks. 12 Group IV (combined valproic acid & liraglutide treated group) received the previously mentioned valproic acid dose plus liraglutide subcutaneously (200 μg/kg body weight) daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration.…”

Section: Significance Statementmentioning

confidence: 99%

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis

Atef,

Abou Hashish,

Hafez

et al. 2023

Cell Biochemistry & Function

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Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon‐like peptide 1 receptor (GLP‐1R) agonist that act as a novel antidiabetic drug with broad‐spectrum anti‐inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA‐induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid‐treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT‐PCR technique. Hepatic NF‐κB and TNF‐α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA‐hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA‐induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.

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Liraglutide treatment attenuates inflammation markers in the cardiac, cerebral and renal microvasculature in streptozotocin‐induced diabetic rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 46 publications

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Effect of sulfasalazine on endothelium-dependent vascular response by the activation of Nrf2 signalling pathway

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis

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