Elimination of etimicin in rat kidneys and alterations of its cytotoxicity to tubular epithelial cells

Etimicin (ETM) can accumulate in kidneys and cause tubular epithelial cell cytotoxicity. This article aims to study ETM elimination in kidneys and its nephrotoxicity, apoptosis, and histopathological insults of renal tubular epithelial cells, after repeated administration. A total of 36 rats were randomly divided into ETM-treated group and vehicle control group. Rats in ETM-treated group were treated intraperitoneally (i.p.) with 100 mg/kg/day ETM and rats in control group received physiological saline (i.p.) for 5 consecutive days. Determination of ETM concentrations accumulated in rat kidneys was carried out by high-performance liquid chromatography on the basis of derivatization with o-phthalaldehyde and by ultraviolet detector. Apoptotic renal tubular epithelial cells were identified by a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Histopathological insults in kidneys were evaluated by hematoxylin and eosin staining. On day 1 after cessation of ETM administration, the accumulation concentration was 347.50 ± 193.30 μg/g tissue; on day 15, ETM concentration became 16.71 ± 9.99 μg/g tissue. Elimination half-life of ETM in rat kidney was about 3.05 days. Apoptotic renal tubular epithelial cells induced by etimicin was recovered gradually from 1544 ± 138 n/mm2 on day 1 to 716 ± 208 n/mm2 on day 15. Histopathological damage was also gradually recovered from vacuolation of tubular epithelial cells as well as renal tubular edema on days 1, 3, and 7 to nearly normal on day 15. From these results, we concluded that renal tubular epithelial cell cytotoxicity induced by ETM can gradually restore with its decreasing concentration in rat kidneys.

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Expression of Fas and Fas Ligand on Mouse Renal Tubular Epithelial Cells in the Generalized Shwartzman Reaction and Its Relationship to Apoptosis

Infection and Immunity ◽

10.1128/iai.67.8.4112-4118.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 4112-4118 ◽

Cited By ~ 13

Author(s):

Naoki Koide ◽

Kayo Narita ◽

Yutaka Kato ◽

Tsuyoshi Sugiyama ◽

Dipshikha Chakravortty ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Fas Ligand ◽

Cell Injury ◽

Tubular Epithelial Cell ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cell ◽

Renal Tubular ◽

Epithelial Cell Injury

ABSTRACT Previously we reported that the consecutive injection of lipopolysaccharide (LPS) into LPS-sensitized mice for the generalized Shwartzman reaction (GSR) appeared to induce the injury of renal tubular epithelial cells via apoptosis. The aim of this study was to characterize the mechanism of renal tubular epithelial cell injury in GSR. The expression of Fas and Fas ligand was immunohistochemically detected on renal tubular epithelial cells from GSR-induced mice, although neither Fas nor Fas ligand was found in cells from untreated control mice or in cells from mice receiving a single injection of LPS. GSR-induced renal tubular epithelial cell injury was produced in neither Fas-negative MRL-lpr/lpr mice nor Fas ligand-negative MRL-gld/gld mice. The administration of anti-gamma interferon antibody together with a preparative injection of LPS prevented the expression of Fas and Fas ligand and the apoptosis of renal tubular epithelial cells. A provocative injection of tumor necrosis factor alpha into LPS-sensitized mice augmented Fas and Fas ligand expression and the apoptosis of renal tubular epithelial cells. The administration of tumor necrosis factor alpha to interleukin-12-sensitized mice resulted in Fas and Fas ligand expression and the apoptosis. Sensitization with interleukin-12 together with anti-gamma interferon antibody did not cause the apoptosis of renal tubular epithelial cells. It was suggested that the Fas/Fas ligand system probably plays a critical role in the development of renal tubular epithelial cell injury through apoptotic cell death.

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PSTPIP2 inhibits cisplatin-induced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells

Cell Death and Disease ◽

10.1038/s41419-020-03267-2 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Hong Zhu ◽

Wenjuan Jiang ◽

Huizi Zhao ◽

Changsheng He ◽

Xiaohan Tang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Epithelial Cell ◽

Epithelial Cells ◽

Histone Acetylation ◽

Kidney Tissue ◽

Kidney Injury ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Cisplatin Nephrotoxicity ◽

Renal Tubular

AbstractCisplatin (CP) is an effective chemotherapeutic agent widely used in the treatment of various solid tumours. However, CP nephrotoxicity is an important limitation for CP use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Recently, we identified a specific role of proline–serine–threonine phosphatase-interacting protein 2 (PSTPIP2) in cisplatin-induced AKI. PSTPIP2 was reported to play an important role in a variety of diseases. However, the functions of PSTPIP2 in experimental models of cisplatin-induced AKI have not been extensively studied. The present study demonstrated that cisplatin downregulated the expression of PSTPIP2 in the kidney tissue. Administration of AAV-PSTPIP2 or epithelial cell-specific overexpression of PSTPIP2 reduced cisplatin-induced kidney dysfunction and inhibited apoptosis of renal tubular epithelial cells. Small interfering RNA-based knockdown of PSTPIP2 expression abolished PSTPIP2 regulation of epithelial cell apoptosis in vitro. Histone acetylation may impact gene expression at the epigenetic level, and histone deacetylase (HDAC) inhibitors were reported to prevent cisplatin-induced nephrotoxicity. The UCSC database was used to predict that acetylation of histone H3 at lysine 27 (H3K27ac) induces binding to the PSTPIP2 promoter, and this prediction was validated by a ChIP assay. Interestingly, an HDAC-specific inhibitor (TSA) was sufficient to potently upregulate PSTPIP2 in epithelial cells. Histone acetylation-mediated silencing of PSTPIP2 may contribute to cisplatin nephrotoxicity. PSTPIP2 may serve as a potential therapeutic target in the prevention of cisplatin nephrotoxicity.

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Caspase 3/GSDME-dependent pyroptosis contributes to chemotherapy drug-induced nephrotoxicity

Cell Death and Disease ◽

10.1038/s41419-021-03458-5 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xiujin Shen ◽

Haibing Wang ◽

Chunhua Weng ◽

Hong Jiang ◽

Jianghua Chen

Keyword(s):

Epithelial Cells ◽

Caspase 3 ◽

Tubular Epithelial Cell ◽

Tubular Epithelial Cells ◽

Chemotherapeutic Drug ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cell ◽

Drug Induced ◽

Jnk Signaling ◽

Renal Tubular

AbstractChemotherapy drug-induced nephrotoxicity limits clinical applications for treating cancers. Pyroptosis, a newly discovered programmed cell death, was recently reported to be associated with kidney diseases. However, the role of pyroptosis in chemotherapeutic drug-induced nephrotoxicity has not been fully clarified. Herein, we demonstrate that the chemotherapeutic drug cisplatin or doxorubicin, induces the cleavage of gasdermin E (GSDME) in cultured human renal tubular epithelial cells, in a time- and concentration-dependent manner. Morphologically, cisplatin- or doxorubicin-treated renal tubular epithelial cells exhibit large bubbles emerging from the cell membrane. Furthermore, activation of caspase 3, not caspase 9, is associated with GSDME cleavage in cisplatin- or doxorubicin-treated renal tubular epithelial cells. Meanwhile, silencing GSDME alleviates cisplatin- or doxorubicin-induced HK-2 cell pyroptosis by increasing cell viability and decreasing LDH release. In addition, treatment with Ac-DMLD-CMK, a polypeptide targeting mouse caspase 3-Gsdme signaling, inhibits caspase 3 and Gsdme activation, alleviates the deterioration of kidney function, attenuates renal tubular epithelial cell injury, and reduces inflammatory cytokine secretion in vivo. Specifically, GSDME cleavage depends on ERK and JNK signaling. NAC, a reactive oxygen species (ROS) inhibitor, reduces GSDME cleavage through JNK signaling in human renal tubular epithelial cells. Thus, we speculate that renal tubular epithelial cell pyroptosis induced by chemotherapy drugs is mediated by ROS-JNK-caspase 3-GSDME signaling, implying that therapies targeting GSDME may prove efficacious in overcoming chemotherapeutic drug-induced nephrotoxicity.

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Gambaran histopatologik ginjal wistar yang diberi ekstrak binahong pasca pemberian gentamisin

Jurnal e-Biomedik ◽

10.35790/ebm.4.2.2016.13911 ◽

2016 ◽

Vol 4 (2) ◽

Author(s):

Zularsil F.W. Rajak ◽

Lily Loho ◽

Poppy Lintong

Keyword(s):

Epithelial Cells ◽

Wistar Rats ◽

Aminoglycoside Antibiotic ◽

Negative Control ◽

Control Group ◽

Tubular Damage ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular ◽

Group B

Abstract: Kidney damage can be caused by many things, such as hypovolemia, sepsis, acute glomeluronefritis, rhabdomyolysis and drugs (gentamicin and NSAID). Gentamicin is an broad spectrum antimicrobial with high toxicity. Gentamicin is an aminoglycoside antibiotic known to be toxic to the kidneys and the side effects that gentamicin cause are renal tubular damage. There are many kinds of herbal plant in Indonesia with benefit, one of them is the binahong plants. Binahong (Anredera cordifoli (Ten) Steenis), has a high antioxidant that is equal to 9.614% of the compound flavonoid.5 Antioxidant contained in binahong leaves can be said as nefroprotective on kidney function. This study aims to reveal the renal histopathologic of wistar rat that have administered binahong extract after gentamicin administration. This study was an experimental study using 25 wistar rats that were divided into 5 groups. Group A is the negative control group (terminated the 7th day), while group B, C, D and E (the treatment group) were administered gentamicin 0.3 ml/day for 6 days. After administration of gentamicin, group B immediately terminated (day 7), group C were administered 50 mg/day of binahong extratct for 3 days (terminated on day 10), group D were administered 100 mg/day of binahong extract for 3 days (terminated on day 10), group E were administered gentamicin for 6 days (terminated on day 10). The results showed that the renal histopathological of wistar rats group that were administered gentamicin for 6 days, showed swelling and necrotic tubular epithelial cells. Wistar rats group that were administered of binahong showed regeneration of renal tubular epithelial cells. Conclusion: The administration of Gentamicin with toxical dose or 0.3 ml/day for 6 days showed acute tubular necrosis. Regeneration of renal tubular epithelial cells is better in the group that were administered binahong extract than the group that were administered pellets. Renal histopathologic of wistar rats at administration of binahong extract with dose of 100 mg are better compared to 50 mg. Keywords: gentamicin, binahong extract, histopathologogical image of wistar rat’s kidney Abstrak: Kerusakan ginjal dapat disebabkan oleh berbagai hal, seperti hipovolemia, sepsis, glomeluronefritis akut, rabdomiolisis dan obat-obatan (Gentamisin dan NSAID). Gentamisin tergolong antibiotika (aminoglikosida) yang berspektrum luas dan memiliki toksisitas tinggi. Salah satu efek toksik dari gentamisin adalah menyebabkan kerusakan pada tubulus ginjal. Ada berbagai jenis tanaman herbal di Indonesia yang mempunyai khasiat, salah satunya adalah tanaman binahong, Tanaman binahong (Anredera cordifoli (Ten) Steenis), memiliki antioksidan yang cukup tinggi yaitu sebesar 9,614% senyawa flavonoid. Antioksidan yang terkandung dalam daun binahong dapat dikatakan sebagai nefroprotektif terhadap fungsi ginjal. Penelitian ini bertujuan untuk mengetahui gambaran histopatologik ginjal tikus wistar yang diberi ekstrak binahong pasca pemberian gentamisin. Penelitian ini merupakan penelitian eksperimental yang menggunakan 25 ekor tikus wistar yang dibagi dalam 5 kelompok. Kelompok A merupakan kelompok kontrol negatif (diterminasi pada hari ke-7), sedangkan kelompok B, C, D dan E (kelompok perlakuan) diberi gentamisin 0,3 ml/hari selama 6 hari. Setelah pemberian gentamisin, kelompok B langsung diterminasi (hari ke-7), kelompok C diberi ekstrak binahong 50 mg/hari selama 3 hari (diterminasi pada hari ke-10), kelompok D ekstrak binahong 100 mg/hari selama 3 hari (diterminasi pada hari ke-10). kelompok E diberi gentamisin selama 6 hari (diterminasi pada hari ke-10). Hasil penelitian menunjukkan bahwa kelompok tikus yang diinduksi gentamisin selama 6 hari secara histopatologik memperlihatkan adanya pembengkakan dan nekrosis sel epitel tubulus. Kelompok tikus yang diberi ekstrak binahong menunjukkan regenerasi sel epitel tubulus ginjal Simpulan: Pemberian gentamisin injeksi dosis toksik yaitu 0,3 ml setiap hari selama 6 hari menunjukkan nekrosis tubular akut (NTA). Regenerasi sel epitel tubulus ginjal lebih baik pada kelompok yang diberi ekstrak binahong dibandingkan kelompok yang hanya diberi pelet. Gambaran histopatologik ginjal lebih baik pada pemberian binahong dengan dosis 100 mg dibandingkan dosis 50 mg.Kata kunci: gentamisin, ekstrak binahong, gambaran histopatologik ginjal.

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Intranuclear Crystals in Regenerating Canine Kidneys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072502 ◽

1973 ◽

Vol 31 ◽

pp. 412-413

Author(s):

D.G. Osborne ◽

L.J. McCormack ◽

M.O. Magnusson ◽

W.S. Kiser

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Tubular Epithelial Cell ◽

Tubular Epithelial Cells ◽

Cell Nuclei ◽

Crystalline Structures ◽

Small Crystals ◽

Membrane Bound

During a project in which regenerative changes were studied in autotransplanted canine kidneys, intranuclear crystals were seen in a small number of tubular epithelial cells. These crystalline structures were seen in the control specimens and also in regenerating specimens; the main differences being in size and number of them. The control specimens showed a few tubular epithelial cell nuclei almost completely occupied by large crystals that were not membrane bound. Subsequent follow-up biopsies of the same kidneys contained similar intranuclear crystals but of a much smaller size. Some of these nuclei contained several small crystals. The small crystals occurred at one week following transplantation and were seen even four weeks following transplantation. As time passed, the small crystals appeared to fuse to form larger crystals.

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