Pentoxifylline mitigates renal glycoxidative stress in obese mice by inhibiting AGE/RAGE signaling and increasing glyoxalase levels

In this study, we pursue determining the effect of pentoxifylline (Ptx) in delayed-onset muscle soreness (DOMS) triggered by exposing untrained mice to intense acute swimming exercise (120 min), which, to our knowledge, has not been investigated. Ptx treatment (1.5, 4.5, and 13.5 mg/kg; i.p., 30 min before and 12 h after the session) reduced intense acute swimming–induced mechanical hyperalgesia in a dose-dependent manner. The selected dose of Ptx (4.5 mg/kg) inhibited recruitment of neutrophils to the muscle tissue, oxidative stress, and both pro- and anti-inflammatory cytokine production in the soleus muscle and spinal cord. Furthermore, Ptx treatment also reduced spinal cord glial cell activation. In conclusion, Ptx reduces pain by targeting peripheral and spinal cord mechanisms of DOMS.

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“…in mice ( Pedretti et al, 2020 ), and 50 mg/kg/i.p. of Ptx does not induce liver or kidney damage in mice ( Inacio et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Brief research report: Repurposing pentoxifylline to treat intense acute swimming–Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms

et al. 2023

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“…Much activation of multiple intracellular cascades depends on the interaction of AGE-RAGE, including NADPH-oxidase/NF-κB and perhaps p21ras/MAPK/AP-1 pathways, and then induces oxidative stress, cellular dysfunction, increased vascular permeability, adhesion molecule expression, cytokine production and initiation of coagulation (Kang et al, 2012). In addition, AGEs themselves or conjugation of RAGE with AGE can activate endoplasmic reticulum (ER) stress-induced inflammatory responses (Inacio et al, 2020). Exogenous AGEs stimulate mesangial cells to produce cytoplasmic reactive oxygen species, which subsequently led to mitochondrial permeability transition and disrupted mitochondrial membrane potential, thereby causing mesangial cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol ameliorates inflammatory response partly by AGE‐RAGE pathway in diabetic mice

Li,

Fan,

et al. 2023

Drug Development Research

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Cannabidiol (CBD), the most abundant nonpsychoactive constituent of Cannabis sativa plant, is a promising potential pharmacotherapy for the treatment of diabetes and associated comorbidities. Previous studies have shown the potential of CBD to prevent diabetes in mice, the precise mechanisms of action remain unclear. The purpose of this study was to explore the mechanism of CBD alleviating hyperglycemia. The results demonstrated that CBD reduced blood glucose of STZ‐induced diabetic mice without causing hypoglycemia. To elucidate the possible mechanisms of CBD effect, RNA‐seq analysis was performed on high glucose‐induced human mesangial cells (HMCs). By cluster analysis of differential genes, the results showed that advanced glycation end products‐receptor of advanced glycation endproducts (AGE‐RAGE) pathway‐related genes CCL2 and interleukin‐1β (IL‐1β) play an important role in the biological of CBD. The expression of CCL2 and IL‐1β were significantly increased in HMCs. Whereas, treatment with CBD decreased the expression of CCL2 and IL‐1β. In addition, CBD significantly reduced AGE‐RAGE levels in high glucose‐induced HMCs. Similar results were confirmed in diabetic mice. In conclusion, we discovered for the first time that CBD ameliorates hyperglycemia partly through AGE‐RAGE mediated CCL2/IL‐1β pathway.

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“…The urinary albumin levels (semi-quantitative analysis) were determined according to Kakani et al [ 26 ] with modifications by Inacio et al [ 27 ] and adaptations for this study. The total protein concentration in 24 h urine samples (after 30 days of treatment) was measured by using the pyrogallol red method [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Lycopene in Combination with Insulin Triggers Antioxidant Defenses and Increases the Expression of Components That Detoxify Advanced Glycation Products in Kidneys of Diabetic Rats

Figueiredo,

Lima,

Carlstrom

et al. 2024

Nutrients

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Background: Biochemical events provoked by oxidative stress and advanced glycation may be inhibited by combining natural bioactives with classic therapeutic agents, which arise as strategies to mitigate diabetic complications. The aim of this study was to investigate whether lycopene combined with a reduced insulin dose is able to control glycemia and to oppose glycoxidative stress in kidneys of diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with 45 mg/kg lycopene + 1 U/day insulin for 30 days. The study assessed glycemia, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma. Superoxide dismutase (SOD) and catalase (CAT) activities and the protein levels of advanced glycation end-product receptor 1 (AGE-R1) and glyoxalase-1 (GLO-1) in the kidneys were also investigated. Results: An effective glycemic control was achieved with lycopene plus insulin, which may be attributed to improvements in insulin sensitivity. The combined therapy decreased the dyslipidemia and increased the PON-1 activity. In the kidneys, lycopene plus insulin increased the activities of SOD and CAT and the levels of AGE-R1 and GLO-1, which may be contributing to the antialbuminuric effect. Conclusions: These findings demonstrate that lycopene may aggregate favorable effects to insulin against diabetic complications resulting from glycoxidative stress.

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Pentoxifylline mitigates renal glycoxidative stress in obese mice by inhibiting AGE/RAGE signaling and increasing glyoxalase levels

Cited by 9 publications

References 44 publications

Brief research report: Repurposing pentoxifylline to treat intense acute swimming–Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms

Brief research report: Repurposing pentoxifylline to treat intense acute swimming–Induced delayed-onset muscle soreness in mice: Targeting peripheral and spinal cord nociceptive mechanisms

Cannabidiol ameliorates inflammatory response partly by AGE‐RAGE pathway in diabetic mice

Lycopene in Combination with Insulin Triggers Antioxidant Defenses and Increases the Expression of Components That Detoxify Advanced Glycation Products in Kidneys of Diabetic Rats

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