Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Kim, Kiryeong; Leem, Jaechan

doi:10.3390/molecules27062019

Cited by 12 publications

(14 citation statements)

References 70 publications

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“…Renal amount of the lipid peroxidation product MDA [ 34 , 35 ] was also reduced by CS (UUO, 6.3 ± 0.6 nmol/mg protein vs. UUO+CS, 3.1 ± 0.4 nmol/mg protein, p < 0.001) ( Figure 5 C). In addition, IF staining for 8-OHdG, an oxidative nucleoside product [ 36 ], revealed that the number of 8-OHdG-positive cells increased after UUO surgery (Sham, 1.1 ± 0.4 vs. UUO, 40.3 ± 4.4, p < 0.001) ( Figure 5 D,E). However, CS treatment remarkably reduced the number of 8-OHdG-positive cells (UUO, 40.3 ± 4.4 vs. UUO+CS, 6.4 ± 1.3, p < 0.001) ( Figure 5 D,E).…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

2022

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Renal fibrosis is a common feature of chronic kidney disease and is a promising therapeutic target. However, there is still limited treatment for renal fibrosis, so the development of new anti-fibrotic agents is urgently needed. Accumulating evidence suggest that oxidative stress and endoplasmic reticulum (ER) stress play a critical role in renal fibrosis. Carnosol (CS) is a bioactive diterpene compound present in rosemary plants and has potent antioxidant and anti-inflammatory properties. In this study, we investigated the potential effects of CS on renal injury and fibrosis in a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice underwent sham or UUO surgery and received intraperitoneal injections of CS (50 mg/kg) daily for 8 consecutive days. CS improved renal function and ameliorated renal tubular injury and interstitial fibrosis in UUO mice. It suppressed oxidative injury by inhibiting pro-oxidant enzymes and activating antioxidant enzymes. Activation of ER stress was also attenuated by CS. In addition, CS inhibited apoptotic and necroptotic cell death in kidneys of UUO mice. Furthermore, cytokine production and immune cell infiltration were alleviated by CS. Taken together, these findings indicate that CS can attenuate renal injury and fibrosis in the UUO model.

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Section: Resultsmentioning

confidence: 99%

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

2022

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“…Renal levels of MDA, another lipid peroxidation product [ 29 ], were also reduced by OXA (CP, 4.5 ± 0.5 nmol/mg protein vs. CP + OXA, 1.8 ± 0.3 nmol/mg protein, p < 0.001) ( Figure 4 C). In addition, OXA reduced renal levels of 8-OHdG, a product of oxidative DNA damage [ 30 ] (CP, 92.6 ± 9.6 ng/g protein vs. CP + OXA, 65.9 ± 6.5 ng/g protein, p < 0.05) ( Figure 4 D). OXA also increased GSH levels (CP, 2.1 ± 0.3 nmol/mg protein vs. CP + OXA, 3.0 ± 0.2 nmol/mg protein, p < 0.01) and GSH/GSSG ratio (CP, 1.1 ± 0.2 vs. CP + OXA, 2.6 ± 0.2, p < 0.001), while decreasing GSSG levels (CP, 1.8 ± 0.2 nmol/mg protein vs. CP + OXA, 1.2 ± 0.2 nmol/mg protein, p < 0.05) ( Figure 4 E–G).…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Kim

Leem

2022

JCM

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Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

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“…HE‐staining results showed that hispidulin could alleviate renal pathological injury, renal interstitial fibrosis, and inflammatory infiltration in UAN rats. Consistently, in LPS‐induced acute kidney injury mice, hispidulin is determined to ameliorate endotoxin‐induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death (Kim & Leem, 2022). In addition, hispidulin is also reported to relieve high‐glucose‐induced podocyte injury by regulating protective autophagy (Wu et al., 2018).…”

Section: Discussionmentioning

confidence: 96%

Study of hispidulin in the treatment of uric acid nephropathy based on NF‐κB signaling pathway

Li,

Gu,

Ren

et al. 2023

Chem Biol Drug Des

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Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin‐C (cys‐C), neutrophil gelatinase‐associated lipocalin (NGAL), IL‐1β, IL‐8, TNF‐α, and IL‐6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys‐C, and NGAL, which all reduced after hispidulin treatment in a dose‐dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL‐1β, IL‐8, TNF‐α, and IL‐6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome‐related proteins of NLRP3 and Caspase‐1 was changeovered by hispidulin. The activation of NF‐kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF‐κB pathway.

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Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Cited by 12 publications

References 70 publications

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Study of hispidulin in the treatment of uric acid nephropathy based on NF‐κB signaling pathway

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