Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity
Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compou...
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223012441 |
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| author | Lina Joo Hye Yun Jeong Dong Hyuck Bae Joo Hyun Jee Woo Hee Choi Hye-Youn Kim Sejoong Kim Dong-Ho Yang Heon Yung Gee SeongGyeong Jeon Yun-Gil Roh Jongman Yoo |
| author_facet | Lina Joo Hye Yun Jeong Dong Hyuck Bae Joo Hyun Jee Woo Hee Choi Hye-Youn Kim Sejoong Kim Dong-Ho Yang Heon Yung Gee SeongGyeong Jeon Yun-Gil Roh Jongman Yoo |
| author_sort | Lina Joo |
| collection | DOAJ |
| description | Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity. |
| first_indexed | 2024-03-11T11:11:54Z |
| format | Article |
| id | doaj.art-be2be5f89b6c4951803d827109b4174c |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:11:54Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-be2be5f89b6c4951803d827109b4174c2023-11-12T04:38:38ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115446Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicityLina Joo0Hye Yun Jeong1Dong Hyuck Bae2Joo Hyun Jee3Woo Hee Choi4Hye-Youn Kim5Sejoong Kim6Dong-Ho Yang7Heon Yung Gee8SeongGyeong Jeon9Yun-Gil Roh10Jongman Yoo11Department of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of KoreaDivision of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, the Republic of KoreaDepartment of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of KoreaDepartment of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of KoreaDepartment of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of Korea; R&D Institute, ORGANOIDSCIENCES LTD., Seongnam, the Republic of KoreaDepartment of Pharmacology, Yonsei University College of Medicine, Seoul 03722, the Republic of KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonnggi-do 13620, the Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine Seoul, 03080, the Republic of KoreaDivision of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, the Republic of KoreaDepartment of Pharmacology, Yonsei University College of Medicine, Seoul 03722, the Republic of KoreaDepartment of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of KoreaProgram in Health Policy, Chung-Buk National University, Republic of KoreaDepartment of Microbiology, CHA University School of Medicine, Seongnam, the Republic of Korea; CHA Organoid Research Center, CHA University, Seongnam, the Republic of Korea; R&D Institute, ORGANOIDSCIENCES LTD., Seongnam, the Republic of Korea; Corresponding author at: Department of Microbiology, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam-si, 13496, the Republic of Korea.Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity.http://www.sciencedirect.com/science/article/pii/S0753332223012441BimatoprostColistinNephrotoxicityDrug repurposingOxidative stressApoptosis |
| spellingShingle | Lina Joo Hye Yun Jeong Dong Hyuck Bae Joo Hyun Jee Woo Hee Choi Hye-Youn Kim Sejoong Kim Dong-Ho Yang Heon Yung Gee SeongGyeong Jeon Yun-Gil Roh Jongman Yoo Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity Biomedicine & Pharmacotherapy Bimatoprost Colistin Nephrotoxicity Drug repurposing Oxidative stress Apoptosis |
| title | Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity |
| title_full | Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity |
| title_fullStr | Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity |
| title_full_unstemmed | Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity |
| title_short | Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity |
| title_sort | prostaglandin f2α analogue bimatoprost ameliorates colistin induced nephrotoxicity |
| topic | Bimatoprost Colistin Nephrotoxicity Drug repurposing Oxidative stress Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223012441 |
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