Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of oxidative stress, inflammation and extracellular matrix remodeling

Abstract

Diabetic peripheral neuropathy is one of the most common microvascular complications that occurs with both type 1 and type 2 diabetes mellitus. It has a significant negative impact on patients' quality of life; as it starts with loss of limbs' sensation and may lead to lower limb amputation. This study aimed at investigating the effect of liraglutide on peripheral neuropathy in diabetic rats. Experimental diabetes was induced by single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were allocated into five groups. Two groups were given saline or liraglutide (0.8 mg/kg, s.c.). Three diabetic groups were either untreated or treated with liraglutide (0.8 mg/kg, s.c.) or pregabalin (10 mg/kg, i.p.). After 2 weeks of treatment, behavioral, biochemical, histopathological, and immunohistochemical investigations were performed. Treatment with liraglutide-restored animals' body weight, normalized blood glucose, decreased glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of both tail flick and hind paw cold allodynia tests and reversed histopathological alterations. Treatment with liraglutide also normalized malondialdehyde, matrix metalloproteinase-2 and -9 contents in sciatic nerve. Likewise, it decreased sciatic nerve nitric oxide and interleukin-6 contents, DNA fragmentation and expression of cyclooxygenase-2. Meanwhile, it increased superoxide dismutase and interleukin-10 contents in sciatic nerve. These findings indicate the neuroprotective effect of liraglutide against diabetic peripheral neuropathy probably via modulating oxidative stress, inflammation, and extracellular matrix remodeling.

Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation

“…High glucose levels have adverse effects on apoptosis, metabolism, proliferation and migration of Schwann cells [ 10 ]. The overproduction of ROS caused by high glucose induces oxidative stress and inflammation, a recognized mechanism in the pathogenesis of DPN [ 6 , 38 ]. This study provides the first evidence that loganin treatment reduces the activation of NLRP3 inflammasomes and subsequent pyroptosis by inhibiting ROS generation in high-glucose-treated RSC96 Schwann cells.…”

“…Excessive activation of P2RX7 and NLRP3 leads to increased inflammatory cytokine secretion, such as IL-1β in depression and diabetes [ 61 ]. Colomar et al pointed out that the maturation and release of interleukin 1β is required to stimulate P2RX7 in lipopolysaccharide-primed mouse Schwann cells [ 38 ]. Gu et al revealed that TXNIP regulates the mechanism of NLRP3 inflammasome activation in diabetic nephropathy [ 39 , 40 ].…”

NFκB mediates the anti-inflammatory actions of liraglutide and sitagliptin in experimentally model of colitis in mice

“…While Sitagliptin, CLS and CSS groups decreased the CRP levels in comparison to A-A group with no signi cant difference than the control group. In a study investigating the effect of liraglutide on peripheral neuropathy in diabetic rats, treatment with liraglutide normalized MDA levels and increased superoxide dismutase level in sciatic nerve [39]. Similarly Varanasi et al (2012) documented a decline in the mean CRP concentration in patients with T2DM treated with liraglutide [40].…”

Interleukin-10 Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis via NF-κB Suppression

“…In experimental diabetic peripheral neuropathy models, sulforaphane or liraglutide normalized motor coordination and the latency withdrawal time of the tail-flick test, increased the latency withdrawal time of the cold allodynia test, and ameliorated histopathological changes. The mechanism of both drugs was partly related to the up-regulation of IL-10 [43,44]. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide exhibits neuroprotection through the autocrine release of IL-10 [45].…”