• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.125-131
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• 1998

Cisplatin is one of the most effective antitumor agents currently available for cancer chemotherapy. However its clinical use has been limited by its severe side effects, especially nephrotoxicity. To evaluate the effect of schizandrin, one of radical scavengers and constituents of Schizandra chimensis, cisplatin and schizandrin were given intraperitoneally. Protective effect of schizandrin against nephrotoxicity of cisplatin was observed when schizandrin was administerd to rats 1,24 hr after cisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and schizandrin was evaluated by measuring sGPT and sGOT. Combination treatment did not affect the levels of sGPT and sGOT. The present result indicate that schizandrin when it is given after cisplatin, may provide protection against cisplatin nephrotoxicity without hepatotoxicity.

• Toxicological Research
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• v.29 no.1
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• pp.61-67
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• 2013

Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d, oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration). Treatments were administered once daily for 12 d. After 12 d, biochemical and histopathological analyses were conducted to evaluate oxidative stress and renal nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant activity. Animals treated with GS alone showed a significant increase in serum levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and CAT. Treatment of rats with HC showed significant improvement in renal function, presumably as a result of decreased biochemical indices and oxidative stress parameters associated with GS-induced nephrotoxicity. Histopathological examination of the rat kidneys confirmed these observations. Therefore, the novel natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative stress in rats.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Korean Journal of Medicinal Crop Science
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• v.25 no.4
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.194-194
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• 2003

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.28-32
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• 2007

Cisplatin, an antitumor agent widely used in the treatment of cancers, has nephrotoxicity. This side effect is closely related to oxidative stress. In the present study, we studied to protective effect of ethanol extract of Bojungbangam-tang (EBJT) on cisplatin-induced nephrotoxicity. Bojungbangam-tang is a new herbal prescription composed of nine crude drugs. Pretreatment of EBJT prevented cisplatin-induced cytotoxicity and generation of ROS. Also, cellular GSH content and gluathione peroxidase activity were recovered by EBJT. EBJT also decreased cisplatin-induced expression of HO-1 via inhibition of ERK activation. Taken together, these results suggest that EBJT has a cytoprotective effect against cisplatin-induced nephrotoxicity through anti-oxidant activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6061-6066
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• 2015

Methotrexate (Mtx), used for its anticancer and immunsuppresive properties, is known to be a nephrotoxic agent. We aimed to investigate the effects of lycopene (Lyc) alone or combined with melatonin (Mel) on Mtxinduced nephrotoxicity since both of these agents have antioxidant and anti-inflammatory effects. Nephrotoxicity was induced by intraperitoneal administration of methotrexate at a dose of 20 mg/kg. Treatment both with Lyc alone and Lyc combined with Mel provided significant reduction in tumor necrosis factor-alpha, interleukin 1-beta and ceruloplasmin levels in Mtx administered rats. Hovewer, Lyc combined with Mel provided a significant reduction also in NO levels. Hstopathological examination showed that there was an obvious improvement in the degenerative changes compared to Mtx administrated group with the Lyc combined Mel group giving best protection. In conclusion Lyc alone and combined with Mel provided significant improvement against renal damage caused by Mtx, preseumably via antioxidant and anti-inflammatory activities.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.133-144
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• 1996

This study investigated the effect of InJinORyungSan on the nephrotoxicity in rat treated with cyclosporin A. Control group were injected with cyclosporin A alone. whereas test group were injected with cyclosporin A and InJinORyungSan extract. In the control group, blood urea nitrogen(BUN), serum creatinine(S-Cr) and renal lipid peroxidation(LPO) level were significantly increased, but renal superoxide dismutase(SOD) activity was significantly decreased. In the kidney of control group, the destruction of distal convoluted tubules(DCT) and proximal convoluted tubules(PCT) were observed in renal cortex, lymphocytes and fibroblast were appeared in the portion of DCT destruction. However, in the test group, BUN, S-Cr and renal LPO level were significantly decreased as compared with control group, on the other hand, renal SOD activity was significantly increased. In the kidney of test group, the destruction of DCT and PCT were repaired as compared with control group. These results demonstrated that InJinORyungSan. can be attributed to recovery from nephrotoxicity, We consider that activated SOD by InJinORyungSan suppress renal LPO or production of free radicals induced by cyclosporin A.

• Advances in Traditional Medicine
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• v.6 no.2
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• pp.108-111
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• 2006

The effect of Kundur (oleo-gum resin of Boswellia serrata) and its fractions viz: methanol soluble (MS) and methanol insoluble (MI) were investigated on mercuric chloride induced nephrotoxicity in rats. The animals of group I and II were administered with 1% carboxymethyl cellulose (CMC) (1,000 mg/kg, p.o.) and the animals of groups III, IV and V were administered with Kundur (1,000 mg/kg, p.o.), MS (650 mg/kg, p.o.) and MI (350 mg/kg, p.o.) respectively for ten days. On 10th day a single dose of the mercuric chloride (3 mg/kg, 5.c.) was also administered to all groups except the group I which received only 1% CMC (10 ml/kg, p.o.). After two days of mercuric chloride administration the blood samples of each animal were collected and analyzed for blood urea nitrogen and creatinine concentration. Rats fed with Kundur and MI fraction showed a significant prevention in the rise of serum markers while MS failed to prevent the rise of these serum makers. These results suggest that Kundur and MI fraction may have potential to reduce the nephrotoxicity in rats.

• Advances in Traditional Medicine
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• v.4 no.1
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• pp.22-27
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• 2004

Cisplatin is a highly effective and extensively used anticancer drug. Higher doses of cisplatin manifest acute nephrotoxicity and this is one of the limiting factors of this drug in cancer chemotherapy. The effect of the oyster mushroom extract to ameliorate cisplatin ( cis platinum (II) diammine dichloride) induced nephrotoxicity and restoration of antioxidant defence system in mice was investigated. The investigations showed that prior administration of methanolic extract of Pleurotus florida at a dose of 500 and 1000mg/Kg body weight significantly reduced elevated serum creatinine and urea levels and increased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the kidney, consequent to cisplatin treatment, in a dose dependent manner. The extract restored the decreased reduced glutathione (GSH) activity and increased malondialdehyde (MDA) level due to cisplatin administration. The results thus indicated that oyster mushroom extract rendered significant protection against cisplatin induced nephrotoxicity and depletion of antioxidant defence system in a dose dependent manner. Since oyster mushrooms are excellently edible and non-toxic, the finding reported here is of significant use in cancer chemotherapy.