Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine); degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65) nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use.
Last. Ramakrishna Sistla(Indian Institute of Chemical Technology)H-Index: 32
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Abstract Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced neph...
Last. Hong-Seob So(Wonkwang University)H-Index: 33
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Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD + is a cofactor for various enzymes associated with cellular homeo...
Abstract Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying...
#1In-Chul Lee(Chonnam National University)H-Index: 16
#2Sung-Hwan Kim(Chonnam National University)H-Index: 16
Last. Jong-Choon Kim(Chonnam National University)H-Index: 35
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Abstract This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl 4 )-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl 4 administration. Pretreatment with DADS attenuated CCl 4 -induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with indu...
Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exe...
Scope Lipid homeostasis in vertebrates is regulated at many levels including synthesis, degradation, and distribution. MicroRNAs (miRNAs) are key regulators of lipid homeostasis. The use of phytochemicals to target miRNA (miR) could provide new therapeutic approaches to human diseases. Thus, we investigated the regulation of lipid metabolism by the flavonoid fisetin during experimental analysis of hepatic miRs in mice. Methods and results Mice were separated into three groups. One group was main...
Last. Michel Tauc(University of Nice Sophia Antipolis)H-Index: 33
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The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic fibrosis transmembrane conductance regulator protein (CFTR), a Cl− channel not only involved in chloride secretion but as well in glutathione (GSH) transport. Thus, we tested whethe...
Last. Deepa Khanna(Chicago, Rock Island and Pacific Railroad)H-Index: 9
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Context Cisplatin, a coordination platinum complex, is used as a potential anti-neoplastic agent, having well recognized DNA-damaging property that triggers cell-cycle arrest and cell death in cancer therapy. Beneficial chemotherapeutic actions of cisplatin can be detrimental for kidneys.
Adipocytes are the key player in adipose tissue inflammation and subsequent systemic insulin resistance and its development involves complex process of proliferation and differentiation of preadipocytes. Fistein, a polyphenol flavonoid, is known to exert anti-inflammatory, anti-carcinogenic and anti-diabetic effects. In this study, we aimed to investigate the effect of fisetin on adipocyte proliferation and differentiation in 3T3-L1 preadipocyte cell line and its mechanism of action. We found th...
#1Ruey Hwang Chou(PRC: China Medical University (PRC))H-Index: 22
#2Shu Ching Hsieh(CSMU: Chung Shan Medical University)H-Index: 9
Last. Yi-Hsien Hsieh(CSMU: Chung Shan Medical University)H-Index: 28
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Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner....
Abstract null null Chronic kidney disease is an increasing burden for public health, especially in older population. Impaired regenerative capacity of endogenous renal stem or progenitor cells is partly responsible for renal tissue fibrosis. Accumulating evidences suggest that stress-induced cellular senescence is involved in acute or chronic kidney injury and may affect reparative cells and impair renal regenerative capacity. Several classes of drugs have been introduced to blunt cellular senes...
#1Maryam Pirani(Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 1
#2Marefat Ghaffari Novin(Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 13
Last. Zahra Shams Mofarahe(Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 5
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Exposure to heat in the male reproductive system can lead to transient periods of partial or complete infertility. The current study aimed to examine the beneficial effects of Fisetin against spermatogenic disorders in mice affected by long-term scrotal hyperthermia. For this purpose, hyperthermia was induced daily by exposure to the temperature of 43 °C for 20 min for 5 weeks. Except for the Healthy group, six other groups were exposed to heat stress: two treated groups including Preventive and...
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 or COVID-19 has been declared as a pandemic disease by the World Health Organization (WHO). Globally, this disease affected 159 million of the population and reported ~ 3.3 million deaths to the current date (May 2021). There is no definitive treatment strategy that has been identified, although this disease has prevailed in its current form for the past 18 months. The main challenges in the (SARS-CoV)-2 infections are in identifying the...
Abstract The graph of drug resistance in cancer is reportedly increasing in terms of therapeutic efficiency. As per the WHO reports, around 70% of death reported in low- and middle-income countries. The increase in death toll was imparted from improper diagnosis and inadequate therapy. The 25% increase in disease burden may be laden due to resistance mutations in cancer during treatment. Exposure of high concentrations of chemotherapeutic agents leads to toxicity in the normal cells. Long-term c...
Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with diffe...
Chlorpyrifos (CPF), a chlorinated organophosphate insecticide that is widely used in agriculture and public health, has neurotoxic effects in animals. In addition to acetylcholinesterase inhibition, CPF has been shown to induce alterations such as oxidative stress and lipid peroxidation. Fisetin is a dietary flavonol that protects the brain tissue against oxidative stress by modulating the activity of antioxidant enzymes. This study was designed to investigate the protective role of fisetin agai...
Aim To evaluate neuroprotective efficacy of fisetin against the experimental model of spinal cord injury (SCI). Materials and methods SCI was induced in male Sprague-Dawley rats by placing an aneurysm clip extradurally. Rats were treated either with vehicle or fisetin for 28 days after SCI. Results Treatment with fisetin significantly attenuated SCI-induced alternations in mechano-tactile and thermal allodynia, hyperalgesia and nerve conduction velocities. SCI-induced upregulated tumor necrosis ...
Last. Mohamed Salama(The: American University in Cairo)H-Index: 2
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Abstract Alzheimer's disease (AD) is the commonest neurodegenerative disorder with a wide array of manifestations, courses, and contributing causes. Despite being clinically characterized a long time ago; no treatment has been developed that could improve the pathology or slow down the disease manifestation- so far. Indian Catechu methanolic extract (ICME) has proved to have multiple beneficial effects that support its use in several disorders- especially those with complex etiology. In the pres...
#1Ge Chenxu(UEW: University of Education, Winneba)H-Index: 4
#2Dai Xianling(UEW: University of Education, Winneba)H-Index: 1
Last. Xu Minxuan(UEW: University of Education, Winneba)H-Index: 4
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Promoted inflammation enhances the development of nephropathy in obesity. Fisetin (3,3',4',7-tetrahydroxyflavone, FIS) is a naturally occurring dietary flavonoid, and exhibits anti-inflammatory and anti-oxidative properties. Inactive rhomboid protein 2 (iRhom2), an inactive member of the rhomboid intramembrane proteinase family, is an essential inflammation-associated regulator. Here, we attempted to investigate the protective mechanisms of FIS against high fat diet (HFD)-induced nephropathy, wi...