Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats

Khames, Ali; Khalaf, Marwa M.; Gad, Amany M.; El‐Raouf, Ola M. Abd

doi:10.1016/j.ejphar.2017.02.046

Cited by 38 publications

(12 citation statements)

References 40 publications

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“…The adriamycin-induced rodent nephrotoxicity model is considered to represent "general" progressive chronic renal disease (Ajith et al, 2008; Lee & Harris, 2011; Taskin, Ozdogan, Kunduz, & Dursun, 2014). Many drugs, such as vitamins, quercetin, and sildenafil, have been applied to treat rodent adriamycin-induced nephropathy even though the detailed mechanism of adriamycin-induced nephropathy remains unclear (Khalil, Mohammed, Abd El-Fattah, & Zaglool, 2018;Khames, Khalaf, Gad, & Abd El-Raouf, 2017;Kumral et al, 2016). Notably, naturally occurring antioxidants, such as vitamins and flavonoids, have been widely studied in the treatment of nephropathy, which is considered to be of great clinical relevance (Injac & Strukelj, 2008).…”

Section: Discussionmentioning

confidence: 99%

Catalpol alleviates adriamycin‐induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro

Zhang

Meng

et al. 2019

British J Pharmacology

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Background and Purpose: Catalpol, a water-soluble active ingredient isolated from Rehmannia glutinosa, exhibits multiple pharmacological activities. However, the mechanism(s) underlying protection against renal injury by catalpol remains unknown. Experimental Approach: Adriamycin-induced kidney injury models associated with podocyte damage were employed to investigate the nephroprotective effects of catalpol. In vivo, TUNEL and haematoxylin-eosin staining was used to evaluate the effect of catalpol on kidney injury in mice. In vitro, effects of catalpol on podocyte damage induced by adriamycin was determined by ELISA kit, flow cytometry, Hoechst 33342, and TUNEL staining. The mechanism was investigated by siRNA, EX527, and docking simulations. Key Results: In vivo, catalpol treatment significantly improved adriamycin-induced kidney pathological changes and decreased the number of apoptotic cells. In vitro, catalpol markedly decreased the intracellular accumulation of adriamycin and reduced the calcium ion level in podocytes and then attenuated apoptosis. Importantly, the regulatory effects of catalpol on sirtuin 1 (SIRT1), multidrug resistance-associated protein 2 (MRP2), and the TRPC6 channel were mostly abolished after incubation with SIRT1 siRNA or the SIRT1-specific inhibitor EX527. Furthermore, docking simulations showed that catalpol efficiently oriented itself in the active site of SIRT1, indicating a higher total binding affinity score than that of other SIRT1 activators, such as resveratrol, SRT2104, and quercetin. Conclusion and Implications: Taken together, our results suggest that catalpol exhibits strong protective effects against adriamycin-induced nephropathy by inducing SIRT1-mediated inhibition of TRPC6 expression and enhancing MRP2 expression. 1 | INTRODUCTION The anthracycline antibiotic adriamycin, a broad-spectrum anti-tumour drug, has been widely used to treat various cancers (Rivankar, 2014). The toxic side effect of adriamycin, mainly associated with cardiotoxicity (Octavia et al., 2012), limits its clinical applications. It has been noted that nephrotoxicity can be induced by adriamycin in rodents but rarely occurs in humans. Anthracycline-induced chronic kidney damage was reported early in 1970 (Sternberg, 1970) and since then animal models of adriamycin-induced kidney injury have been widely established (Bucciarelli, Binazzi, Santori, & Vespasiani, 1976; Chen et al., 2015). It has been reported that the adriamycin-induced classic nephrotoxicity model is very similar to human progressive chronic renal disease (Ajith, Aswathy, & Hema, 2008). Subsequently, Jiangnan Zhang and Ran Bi should be considered joint first author.

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Section: Discussionmentioning

confidence: 99%

Catalpol alleviates adriamycin‐induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro

Zhang

Meng

et al. 2019

British J Pharmacology

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“…divided on three injections (6 mg/kg) every week for 3 consequent weeks. This was according to a pilot study for the dose modified from [1,18,24,25], i.e. DXR was given to the animals at the 1 st , 8 th and 15 th day of the study.…”

Section: Experimental Groupsmentioning

confidence: 99%

Boswellic acids ameliorate doxorubicin-induced nephrotoxicity in mice: a focus on antioxidant and antiapoptotic effects

Sami

Ali

Galhom

et al. 2019

Egyptian Journal of Basic and Applied Sciences

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Doxorubicin (DXR) is a broad-spectrum anti-cancer. Doxorubicin irreversible toxicity resulting from oxidative damage limits its therapeutic use. Boswellic acids (BAs) are inhibitors of 5-lipoxygenase and have been used in traditional medicine for their powerful anti-inflammatory effects and cellular protective effects. This study tested the protecting mechanisms of BAs against nephrotoxicity induced by DXR in mice and explored their antioxidant and antiapoptotic activities in the form of immunohistochemical expression of Bcl2 in the tissue of the kidney. DXR (6 mg/kg) was injected intraperitoneally weekly to mice along with BAs (125, 250 and 500 mg/kg) daily. The experiment continued for three weeks. It was found that the elevated serum urea and creatinine in DXR-treated mice were ameliorated by BAs. Furthermore, BAs decreased malondialdehyde and increased glutathione levels in renal tissues of DXR-treated mice. The immunostained kidney tissue showed an antiapoptotic effect for BAs as it increased expression of Bcl2 in mice co-treated with BAs with DXR compared to the DXR control mice. Western blot analysis demonstrated that DXR control group showed greater expression for renal caspase 3 and mice administered BAs (125-500 mg/kg) along with DXR showed significant downregulations. These findings were supported by the DNA laddering assay and histopathological examination of renal tissues stained with haematoxylin+eosin or periodic acid Schiff. Results suggest BAs for nephroprotection against toxicity induced by DXR.

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“…It is generally recognized that inflammation and oxidative stress are central pathogenic factors in the progression of ADR-induced NS [34,37]. ADR has been reported to result in direct oxidative damage to DNA and induce generation of lipid peroxidation [41].…”

Section: Discussionmentioning

confidence: 99%

“…The mice were anesthetized and sacrificed on day 25, and the left kidney was removed and then homogenized as mentioned anteriorly [34]. The SOD activity and MDA level in plasma and kidney homogenate were detected according to the protocols of corresponding assay kit from Nanjing Jiancheng Bioengineering Institute (Nanjing, China), respectively.…”

Section: Experimental Verification Determination Of Renal Oxidative Smentioning

confidence: 99%

Exploring protective effect of Glycine tabacina aqueous extract against nephrotic syndrome by network pharmacology and experimental verification

Tan

Wang

et al. 2020

Chin Med

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Background: Glycine tabacina (Labill.) Benth, one of the traditional Chinese herbal medicines, has been used for treatment of nephritis, osteoporosis, rheumatism, and menopausal syndrome. The aim of this study was to illuminate the therapeutic effect and mechanism of Glycine tabacina aqueous extract (GATE) in the treatment of nephrotic syndrome (NS). Methods: UHPLC-DAD-MS/MS was used to analyze the chemical profile of GATE. Adriamycin (ADR)-induced NS mouse model and network pharmacology methods were conducted to explore the protective effect and mechanism of GATE on NS treatment. Results: GATE administration significantly ameliorated symptoms of proteinuria and hyperlipidemia in NS mice, as evidenced by reduced excretion of urine protein and albumin, and decreased plasma levels of total cholesterol and triglyceride. Decreased blood urea nitrogen (BUN) and creatinine levels in NS mice suggested that GATE could prevent renal function decline caused by ADR. GATE treatment also inhibited ADR-induced pathological lesions of renal tissues as indicated by periodic acid Schiff staining. Six flavonoids of GATE were identified by using UHPLC-DAD-MS/ MS. Network pharmacology analysis indicated that the protection of GATE in treating NS might be associated with the regulation of oxidative stress and inflammation. In addition, the in vivo experiment validated that treatment with GATE markedly decreased reactive oxygen species production, malonaldehyde level, and increased superoxide dismutase activity both in plasma and renal tissues. TNF-α level in plasma and protein expression in kidney were significantly decreased in GATE treatment groups. Conclusions: Combination of network pharmacology analysis and experimental verification revealed that GATE exerts anti-NS effect possibly through modulating oxidative stress and inflammation, suggesting the potential application of GATE or its derivatives in the prevention and treatment of NS and other related kidney diseases.

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Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats

Cited by 38 publications

References 40 publications

Catalpol alleviates adriamycin‐induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro

Catalpol alleviates adriamycin‐induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro

Boswellic acids ameliorate doxorubicin-induced nephrotoxicity in mice: a focus on antioxidant and antiapoptotic effects

Exploring protective effect of Glycine tabacina aqueous extract against nephrotic syndrome by network pharmacology and experimental verification

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