Phospholipase A2 inhibitor varespladib prevents wasp sting-induced nephrotoxicity in rats

Wang, Rui; Gao, Dan; Yu, Fanglin; Han, Jiamin; Yuan, Hai; Hu, Fengqi

doi:10.1016/j.toxicon.2022.06.007

Cited by 5 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AKI pathogenesis in the wasp venom-induced AKI in vivo model was confirmed to be secondary to rhabdomyolysis and intravascular hemolysis [ 5 ]. In addition, using this model, we further demonstrated that myoglobin reabsorption and PLA2 may be potential targets for treating wasp venom-induced AKI [ 41 , 42 ]. Tang et al.…”

Section: From Clinical Renal Biopsy To An Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

Wasp venom-induced acute kidney injury: current progress and prospects

Yu,

Wang,

Yuan

et al. 2023

Renal Failure

Self Cite

View full text Add to dashboard Cite

Wasp venom can trigger local and systemic reactions, with the kidneys being commonly affected, potentially causing acute kidney injury (AKI). Despite of the recent advances, our knowledge on the underlying mechanisms of toxicity and targeted therapies remain poor. AKI can result from direct nephrotoxic effects of the wasp venom or secondary rhabdomyolysis and intravascular hemolysis, which will release myoglobin and free hemoglobin. Inflammatory responses play a central role in these pathological mechanisms. Noteworthily, the successful establishment of a suitable experimental model can assist in basic research and clinical advancements related to wasp venom-induced AKI. The combination of therapeutic plasma exchange and continuous renal replacement therapy appears to be the preferred treatment for wasp venom-induced AKI. In addition, studies on cilastatin and varespladib for wasp venom-induced AKI treatment have shown their potential as therapeutic agents. This review summarizes the available evidence on the mechanisms and treatment of wasp venom-induced AKI, with a particular focus on the role of inflammatory responses and potential targets for therapeutic drugs, and, therefore, aiming to support the development of clinical treatment against wasp venom-induced AKI.

show abstract

Section: From Clinical Renal Biopsy To An Animal Modelmentioning

confidence: 99%

“…We are inclined to agree with that interpretation and suppose that rhabdomyolysis was the primary mechanism of wasp venom-induced AKI. Our recent animal study further demonstrated that myoglobin is one of the most upregulated genes in the AKI group compared with the normal group [ 42 ].…”

Section: Aki Pathophysiology Induced By Wasp Venommentioning

confidence: 99%

Wasp venom-induced acute kidney injury: current progress and prospects

Yu,

Wang,

Yuan

et al. 2023

Renal Failure

Self Cite

View full text Add to dashboard Cite

show abstract

“…Heme, the core chemical structure in hemoglobin and myoglobin [ 21 ], has been implicated in triggering rapid complement deposition in the kidney [ 10 ]. Our previous study revealed that heme oxygenase 1, a critical enzyme for heme metabolism, is one of the most upregulated genes in a rat model of wasp venom-induced AKI [ 22 ], suggesting the significant role of heme in AKI induced by wasp venom. The indirect effects of heme, resulting from rhabdomyolysis and intravascular hemolysis, may contribute to complement activation in the kidney of a wasp venom-induced AKI model.…”

mentioning

confidence: 99%

“…Previous studies have provided evidence that local complement activation in the kidney can induce cell death and inflammation during AKI development [ 12 , 25 ]. Our previous studies have shown that cell death (apoptosis, necroptosis) and inflammation in the kidney are significant features of wasp venom-induced AKI [ 17 , 22 ]. Additionally, C5b-9 has been found to play a pathological role in the kidneys.…”

mentioning

confidence: 99%

“…C5b-9 may contribute to wasp venom-induced AKI by inducing kidney cell death and promoting inflammation. Our recent studies have highlighted the significant contribution of cell death and inflammation to the development of AKI induced by wasp venom [ 11 , 17 , 22 ]. These findings suggest an association between complement activation and cell death and inflammation in wasp venom-induced AKI.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Complement activation in wasp venom-induced acute kidney injury

Cheng,

Xu,

Gong

et al. 2024

Renal Failure

Self Cite

View full text Add to dashboard Cite

Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

show abstract

STING deficiency protects against wasp venom-induced acute kidney injury

Liu

Lü

et al. 2023

Inflamm. Res.

View full text Add to dashboard Cite

Phospholipase A2 inhibitor varespladib prevents wasp sting-induced nephrotoxicity in rats

Cited by 5 publications

References 33 publications

Wasp venom-induced acute kidney injury: current progress and prospects

Wasp venom-induced acute kidney injury: current progress and prospects

Complement activation in wasp venom-induced acute kidney injury

STING deficiency protects against wasp venom-induced acute kidney injury

Contact Info

Product

Resources

About