• Archives of Pharmacal Research
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• v.22 no.4
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• pp.367-371
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• 1999

Effects of several durgs on rabbit renal proximal tubules were examined for the applicability of renal dipeptidase (RDPase, EC 3. 4. 13. 11) release as a model system to study nephrotoxicity. The proximal tubule prepared by the method of Taub (1990) released RDPase spontaneously in the control experiment which was confirmed by Western blotting. RDPase was also released form cisplatin, lipopolysaccardie (LPS), and indomethacin-treated tubules. Gentamicin inhibited RDPase release in a concentration-dependent manner. This RDPase release system may not be a general model to screen nephrotoxicity but could be a useful source of RDPase purification in a simple and inexpensive way.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.250.2-251
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• 2003

There are contradicting reports on the nephrotoxicity of heptaplatin, a new platinum derivative. A retrospective study was performed to compare the toxicities of heptaplatin-containing regimens with the ones not. Seventy-seven patients with advanced gastric cancer who did not receive any chemotherapy within the last 3 months before the treatment were evaluated. Among them 38 patients received heptaplatin-containing regimens (heptaplatin/epirubicin/5-FU: 26, heptaplatin/5-FU: 12) and 39 patients received other regimens (cisplatin/epirubicin/5-FU:11, epirubicin/leucovorin/5-FU: 28). (omitted)

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Korean Journal of Veterinary Research
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• v.59 no.3
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• pp.133-139
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• 2019

Autophagy is a fundamental cellular process that maintains homeostasis and cell integrity, under stress conditions. Although the involvement of autophagy in various conditions has been elucidated, the role of autophagy in renal structure is not completely clarified. Our aim was to investigate the cytoprotective effect of autophagy against acute kidney injury (AKI) through cisplatin deteriorative pathway, which leads to AKI via renal cell degradation. For in vivo experiments, male Sprague Dawley rats were divided in to 2 groups (n = 6/group) as control, Cis-5D. Following a single intraperitoneal injection of cisplatin, rats were sacrificed after 5 days. Blood urea nitrogen (BUN), creatinine (Cr) and histological alterations were examined. Further, expression of key regulators of autophagy, light-clain 3 (LC3), p62, and Beclin1, was evaluated by immunohistochemistry (IHC). The rats exhibited severe renal dysfunction, indicated by elevated BUN, Cr. Hematoxylin and eosin staining revealed histological damages in cisplatin-treated rats. Furthermore, IHC analysis revealed increased expression of LC3, Beclin1 and decreased expression of p62. Furthermore, expression of aforementioned autophagy markers was restricted to proximal tubule. Taken together, our study demonstrated that cisplatin can cause nephrotoxicity and lead to AKI. This phenomenon accelerated autophagy in renal proximal tubules and guards against AKI.

• 대한임상약리학회:학술대회논문집
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• 2001.12a
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• pp.27-28
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• 2001

• Microbiology and Biotechnology Letters
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• v.32 no.3
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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.

• 한국약용작물학회:학술대회논문집
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• 2008.05a
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• pp.190-191
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• 2008

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.208.3-209
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• 2002

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.358.2-358.2
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• 2002

Platinum(II) coordination complex(cisplatin) has been currently used as one of the most effective compounds in the treatment of various solid tumors. However. its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.395-401
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• 1998

We have synthesized new platinum(II) analogs containing 1,2-diaminocyclohexane (dach) as a carrier ligand, 1,3-bis(diphenylphosphino) propane (DPPP) /1,2-bis(diphenylphosphino)ethane (DPPE) as a leaving group and nitrates to improve solubility. In the present study, the cytotoxicity of $[Pt(trans-l-dach)(DPPP)]\;2NO_3$ (KHPC-001) and $[Pt(trans-l-dach)(DPPE)]\;2NO_3$ (KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine kidney cell line ($LLC-PK_1$). The new platinum complexes demonstrated high efficacy on P-388 mouse leukemia cell line as well as cisplatin-resistant (P-388/CDDP) and adriamycin-resistant (P-388/ADR) P-388 cell lines. The intracellular platinum content was measured by a flame atomic absorption spectrophotometer (FAAS), and it was comparable to the results of $IC_{50}$ of the three complexes on $LLC-PK_1$ and P-388/S cells, while only DPPE compound was accumulated in high volume in P-388/ADR and P-388/CDDP cells. While the DNA-interstrand cross-links of KHPC-001, KHPC-002 and cisplatin were similar on P-388/S leukemia cells, these new platinum complexes were much less DNA cross-linking to a kidney derived cell line, $LLC-PK_1$. These results indicate that KHPC-001 and KHPC-002 are a third-generation platinum complexes with potent antitumor activity and low nephrotoxicity.