Ameliorating Effect of Pentadecapeptide Derived from Cyclina sinensis on Cyclophosphamide-Induced Nephrotoxicity

Jiang, Xiaoxia; Ren, Zhexin; Zhao, Bin; Zhou, Shuyao; Ying, Xiaoguo; Tang, Yunping

doi:10.3390/md18090462

Cited by 24 publications

(28 citation statements)

References 34 publications

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“…[23 -25] Indeed, numerous reports have shown that CTX depleted antioxidant enzymes (SOD, GSH, CAT and GPx), increased ROS and lipid peroxidation in the kidney, testes, liver and bladder of CTX exposed animals. [10,23,26] Likewise, the results obtained from this study indicated renal oxidative damage in the CTX treated animals as evident by significant declines in renal activities of SOD, CAT, GSH and GPx, while MDA content was increased. SRPF displayed significant antioxidant activity via restoration of renal antioxidant capacities (elevated SOD, CAT, GPx and GSH activities as well as decreased MDA level).…”

Section: Discussionsupporting

confidence: 63%

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations

Tong

Zhou

et al. 2022

Chemistry & Biodiversity

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Cyclophosphamide (CTX) is one of the most commonly used alkylating agents for the treatment of various cancers; however, CTX‐induced nephrotoxicity is one of the most prevailing side effects of the drug. Shorea roxburghii is a plant with diverse bioactivities including antioxidant, anti‐inflammatory and renoprotective effects. This study investigated the nephroprotective effect of Shorea roxburghii phenolic extract (SRPF) against CTX‐induced nephrotoxicity in rats. The rats were treated with SRPF (100 and 400 mg/kg) for 5 weeks and were concomitantly administered with CTX. The results indicated that treatment with SRPF significantly decreased serum creatinine, blood urea nitrogen (BUN), uric acid as well as renal MDA, IL‐6, TNF‐α, IL‐1β, NF‐kB and caspase‐3 levels. Furthermore, SRPF augmented the activities of renal SOD, CAT, GSH and GPx. SRPF also improved renal histopathological damages caused by CTX administration. In conclusion, these results suggested that SRPF showed substantial protective effects against CTX‐mediated renal toxicity via its antioxidant and anti‐inflammatory effects.

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Section: Discussionsupporting

confidence: 63%

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations

Tong

Zhou

et al. 2022

Chemistry & Biodiversity

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“…Research has revealed that CYP treatment promoted the level of apoptotic protein in mice (Jiang et al. 2020 ). To evaluate the anti-apoptotic role of HQH in CYP-treated rats, we determined the expression of caspase-3, caspase-9, and the ratio of the pro-apoptotic protein Bax to the anti-apoptotic protein Bcl-2 by western blot ting analysis ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation

Zhang

Chang

Gao

et al. 2021

Pharmaceutical Biology

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Context Severe nephrotoxicity greatly limits the clinical use of the common effective chemotherapeutic agent cyclophosphamide (CYP). Huaiqihuang (HQH) is a Chinese herbal complex with various pharmacological activities, widely used for treating kidney disease. Objective This study estimates the protective effect of HQH against CYP-induced nephrotoxicity in rats. Materials and methods Four groups of 10 Sprague-Dawley rats were pre-treated with once-daily oral gavage of 3 and 6 mg/kg HQH for 5 days before receiving a single dose of CYP (200 mg/kg i.p.) on the 5th day; the control group received equivalent dose of saline. Renal function indices, morphological changes, oxidative stress, apoptosis and inflammatory mediators were measured. In addition, phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were analysed. Results Both doses of HQH reduced the levels of serum creatinine (31.27%, 43.61%), urea nitrogen (22.66%, 32.27%) and urine protein (12.87%, 15.98%) in the CYP-treated rats, and improved histopathological aberrations. Additionally, HQH decreased the production of MDA (37.02%, 46.18%) and increased the activities of antioxidant enzyme CAT (59.18%, 112.25%) and SOD (67.10%, 308.34%) after CYP treatment. HQH protected against CYP-induced nephrotoxicity by modulating apoptosis-related protein and suppressing the inflammatory responses. Furthermore, the phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were significantly boosted in CYP-treated rats, which was also abrogated by HQH treatment. Conclusions HQH effectively protected against CYP-induced nephrotoxicity, which was associated with regulating oxidative stress, apoptosis and inflammation, and so HQH may be a useful agent for treating nephrotoxicity caused by CYP.

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“…8,9 CTX, as an inactive prodrug, enters into the human body and forms the unstable 4-hydroxycyclophosphamide through the metabolic transformation of the cytochrome P450 (CYP450) enzyme, then generates phosphoramide mustard and acrolein. [10][11][12] Phosphoramide mustard is an effective metabolite of CTX, which kills cancer cells. It can alkalize cellular nucleic acids and inhibit the proliferation and division of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…Cyclophosphamide (CTX) is a popular broad‐spectrum anticancer agent used in clinical practice 8,9 . CTX, as an inactive prodrug, enters into the human body and forms the unstable 4‐hydroxycyclophosphamide through the metabolic transformation of the cytochrome P450 (CYP450) enzyme, then generates phosphoramide mustard and acrolein 10‐12 . Phosphoramide mustard is an effective metabolite of CTX, which kills cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Laminaria japonica fucoidan ameliorates cyclophosphamide‐induced liver and kidney injury possibly by regulating Nrf2/HO‐1 and TLR4/NF‐κB signaling pathways

et al. 2021

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BACKGROUND: During clinical practice, cyclophosphamide (CTX) can lead to liver and kidney injury in vivo. In this study, we established a liver and kidney injury model by injecting CTX (80 mg kg −1 d −1 ) into male ICR mice, and then mice were treated with saline and fucoidan (20 or 40 mg kg −1 ), respectively. Subsequently, the liver and kidney toxicity indices, the expression levels of malonic dialdehyde (MDA), inflammatory factors, and the main protein levels of the Nrf2/HO-1 and TLR4/NF-κB pathways were determined. RESULTS: Our results indicated that fucoidan could significantly decrease serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and urea (BUN) in the test group compared to the model group. Fucoidan administration caused reductions in MDA, interleukin-6 (IL-6), IL-1⊎, and tumor necrosis factor alpha (TNF-⊍) levels and improved superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the liver and kidney of CTXinduced mice. Fucoidan up-regulated the Nrf2/HO-1 pathway and enhanced the protein levels of Nrf2, HO-1, GCLM, and NQO1. Moreover, fucoidan down-regulated the TLR4/NF-κB pathway, as indicated by decreased levels of TLR4, NF-κB p65, NF-κB p50, and increased IκB⊍ level in liver and kidney tissues. CONCLUSION: Our studies suggest that fucoidan can ameliorate CTX-induced liver and kidney injury, potentially via upregulating the Nrf2/HO-1 pathway and inhibiting the TLR4/NF-κB pathway.

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Ameliorating Effect of Pentadecapeptide Derived from Cyclina sinensis on Cyclophosphamide-Induced Nephrotoxicity

Cited by 24 publications

References 34 publications

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation

Laminaria japonica fucoidan ameliorates cyclophosphamide‐induced liver and kidney injury possibly by regulating Nrf2/HO‐1 and TLR4/NF‐κB signaling pathways

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