• 한국미생물·생명공학회지
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• 제32권3호
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• pp.271-276
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• 2004

$\beta$-Immunan was proteoglycan obtained from mycelium of Ganoderma lucidum IY009. In this study, the protective effects of $\beta$-Immunan, against the CDDP induced in vitro cytotoxicity and in vivo renal toxicity, was measured. Concentration dependent cytotoxicities of CDDP in normal kidney cells (Vero, TCMK-l) were reduced by $\beta$-Immunan treatment. Increased renal toxicity factors, such as elevation of blood urea nitrogen (BUN) and serum creatinine, reduction of kidney weight and malonidialdehyde (MDA), by intraperitoneal administration of CDDP in rats was improved. These results indicated that $\beta$-Immunan have a protective effects against the CDDP induced renal toxicity, however, it needed to confirm the detailed mechanism for therapeutic effects.

• 한국한의학연구원논문집
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• 제7권1호
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• pp.135-144
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• 2001

Objectives : This study was carried out to research the protective effects of Sagunja-Tang(SA) through in vivo experiments, and tried to investigate the relation between oxidation of renal tissues and deficiency of Qi. Methods : Acute renal injury which initiated from free radical induced by $HgCl_2$, were applied to mice and metabolic data were obtained. In order to measure the degree of renal injury, serum level of creatinine, blood urea nitrogen(BUN), total protein(TP) and glucose were measured. Besides, serum level of alanine aminotransferase(AST), aspartate aminotransferase(ALT) were measure too. Lipid peroxidation of renal cortex was examined by measuring malondialdehyde(MDA), a product of lipid peroxidation. Results : SA had protective effects on acute renal injury caused by decrease of glomerular filtration which was initiated by subcutaneous injection of $HgCl_2$. SA protected acute liver injury too. Conclusions : Through this study, we found that SA have healing effects on renal injury of $HgCl_2$ induced oxidative stress that is similar to deficiency of Qi. And further studies have to be followed to certify the mechanisms.

• Food Science and Biotechnology
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• 제16권6호
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• pp.988-993
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• 2007

The protective effect of the water extract of Fraxinus rhynchophylla leaves (FLE) was determined using an animal model of acetaminophen (AAP)-induced nephrotoxicity. The BALB/c male mice used in this study were divided into 3 groups; the normal, AAP-administered, and FLE-pretreated AAP groups. A single dose of AAP induced necrosis of renal tubules and congestion along with edema to a remarkable degree as observed by hematoxylin and eosin stain, and also increased the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive renal tubular epithelial cells. Blood urea nitrogen and plasma creatinine levels were determined to be significantly higher in the AAP group than in the normal group. However, FLE pretreatment resulted in an attenuation of renal tubule necrosis. Regeneration and dilatation of renal tubules were noted, and the numbers of TUNEL-positive cells were reduced in the FLE-pretreated groups. In an effort to detect the bioactive compounds exerting protective effects in FLE, the analysis of phenolic compounds via gas chromatography/mass spectrometry (GC/MS) were performed, and identified esculetin and esculin. The present study indicates that these compounds may exert a protective effect against AAP-induced nephrotoxicity.

• Molecules and Cells
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• 제39권6호
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• pp.508-513
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• 2016

To investigate the potential therapeutic effects of polyphenols in treating Pb induced renal dysfunction and intoxication and to explore the detailed underlying mechanisms. Wistar rats were divided into four groups: control groups (CT), Pb exposure groups (Pb), Pb plus Polyphenols groups (Pb+PP) and Polyphenols groups (PP). Animals were kept for 60 days and sacrificed for tests of urea, serum blood urea nitrogen (BUN) and creatinine. Histological evaluations were then performed. In vitro studies were performed using primary kidney mesangial cells to reveal detailed mechanisms. Cell counting kit-8 (CCK-8) was used to evaluate cell viability. Pb induced cell apoptosis was measured by flow cytometry. Reactive oxygen species (ROS) generation and scavenging were tested by DCFH-DA. Expression level of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1-${\beta}$ (IL-1-${\beta}$) and IL-6 were assayed by ELISA. Western blot and qPCR were used to measure the expression of ERK1/2, JNK1/2 and p38. Polyphenols have obvious protective effects on Pb induced renal dysfunction and intoxication both in vivo and in vitro. Polyphenols reduced Pb concentration and accumulation in kidney. Polyphenols also protected kidney mesangial cells from Pb induced apoptosis. Polyphenols scavenged Pb induced ROS generation and suppressed ROS-mediated ERK/JNK/p38 pathway. Downstream pro-inflammatory cytokines were inhibited in consistency. Polyphenol is protective in Pb induced renal intoxication and inflammatory responses. The underlying mechanisms lie on the antioxidant activity and ROS scavenging activity of polyphenols.

• Molecules and Cells
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• 제37권3호
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• pp.234-240
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• 2014

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

• Natural Product Sciences
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• 제26권1호
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• pp.28-49
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• 2020

The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.321-331
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• 2021

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

• Journal of Acupuncture Research
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• 제18권4호
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• pp.143-151
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• 2001

Objective : This study was undertaken to determine whether Scutellaria balicalensis Georgi (SbG) extract exerts the protective effect against oxidant-induced alterations in organic cation transport in the renal proximal tubule. Methods : Organic cation transport was estimated by examining alterations in tetraethylammon - ium(TEA) uptake in rabbit renal cortical slices. The slices were treated with 0.2 mM tBHP for 60 min at $37^{\circ}C$. tBHP caused an inhibition in TEA uptake by renal cortical slices. Such an effect was accompanied by depressed Na+-K+-ATPase activity and ATP depletion. tBHP also induced a significant increase in LDH release. Results : SbG prevented tBHP-induced inhibition of TEA uptake in a dose-dependent manner at the concentration ranges of 0.05-0.1%. tBHP-induced inhibition of Na+-K+-ATPase activity and ATP depletion were significantly prevented by 0.05% SbG. tBHP-induced LDH release also was blocked by SbG. tBHP caused a significant increase in lipid peroxidation and its effect was prevented by SbG. Conclusion : These results suggest that SbG prevents oxidant-induced alterations in organic cation transport in rabbit renal cortical slices. Such protective effects of SbG may be attributed to inhibition of peroxidation of membrane lipid.

• Journal of Ginseng Research
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• 제41권2호
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• pp.188-194
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• 2017

Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the $4^{th}$ d. Results: The DPPH radical-scavenging activity of FBG ($IC_{50}=384{\mu}g/mL$) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of $NF-{\kappa}B/p65$, COX-2, and caspase-3 activation. Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.

• 대한약침학회지
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• 제4권2호
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• pp.49-56
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• 2001

This study was undertaken to determine whether Scutellaria baicalensis Georgi (SbG) extract exerts the protective effect against $HgCl_2$-induced alterations in membrane transport function in rabbit renal cortical slices. The slices were treated with 0.1 mM $HgCl_2$ for 60 min at $37^{\circ}C$. $HgCl_2$ caused an inhibition in PAH uptake by renal cortical slices. Such an effect was accompanied by depressed $Na^+-K^+$-ATPase activity and ATP depletion. SbG prevented $HgCl_2$-induced inhibition of PAH uptake in a dose-dependent manner at the concentration ranges of 0.01-0.1%. $HgCl_2$-induced inhibition of $Na^+-K^+$-ATPase activity and ATP depletion were significantly prevented by 0.05% SbG. These results suggest that SbG prevents $HgCl_2$-induced alterations in membrane transport function in rabbit renal cortical slices. Such protective effects of SbG may be attributed to inhibition of peroxidation of membrane lipid.