{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T21:34:22Z","timestamp":1782164062463,"version":"3.54.5"},"reference-count":56,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>In the present study, the protective effect of Roflumilast (ROF, a selective phosphodiesterase (PDE-4) inhibitor) was investigated against cadmium (Cd)-induced nephrotoxicity in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A total of 24 rats were selected and randomly divided into four groups ( n = 6). Group 1 served as the control; groups 2\u20134 administered with CdCl\n                      <jats:sub>2<\/jats:sub>\n                      (3 mg\/kg, i.p.) for 7 days; groups 3 and 4 were co-administered with ROF in doses of 0.5 and 1.5 mg\/kg, orally for 7 consecutive days. Nephrotoxicity was evaluated by measuring urine volume, urea and creatinine levels in urine and serum. Oxidative stress was confirmed by measuring malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in kidney tissue followed by histopathological studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      CdCl\n                      <jats:sub>2<\/jats:sub>\n                      administration results in a significant ( p &lt; 0.01) decrease in urine volume, urea, and creatinine levels in urine, as well as GSH, SOD, and CAT levels in renal tissue. In addition, Cd also produced significantly increased ( p &lt; 0.01) urea and creatinine levels in serum and TBARS levels in renal tissues. Rats treated with ROF significantly ( p &lt; 0.01) restore the altered levels of kidney injury markers, nonenzymatic antioxidant, as well as depleted enzymes in dose-dependent manner. An increased expression of NF-\u03baB p65 and decreased expression of GST and NQO1 in the Cd only treated group were significantly reversed by high dose of ROF (1.5 mg\/kg). Histopathological changes were also ameliorated by ROF administration in Cd-treated groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In conclusion, ROF treatment showed protective effect against renal damage and increased oxidative stress induced by Cd administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0960327119829521","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T15:40:02Z","timestamp":1549986002000},"page":"588-597","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":31,"title":["Roflumilast, a phosphodiesterase 4 inhibitor, attenuates cadmium-induced renal toxicity via modulation of NF-\u03baB activation and induction of NQO1 in rats"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-3002","authenticated-orcid":false,"given":"MN","family":"Ansari","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RI","family":"Aloliet","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MA","family":"Ganaie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TH","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Najeeb-ur-Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Imam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-7916","authenticated-orcid":false,"given":"AM","family":"Hamad","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Preparatory year Deanship, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia"},{"name":"Department of Histopathology and Cytopathology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Madani, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"bibr1-0960327119829521","doi-asserted-by":"publisher","DOI":"10.3390\/molecules161210443"},{"key":"bibr2-0960327119829521","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/457327"},{"key":"bibr3-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2007.07.007"},{"key":"bibr4-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.12.024"},{"key":"bibr5-0960327119829521","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4103\/sjfms.sjfms_7_17","volume":"1","author":"Ibrahim MA","year":"2018","journal-title":"Saudi J Forensic Med Sci"},{"key":"bibr6-0960327119829521","first-page":"45","volume":"45","author":"Galley HF","year":"2000","journal-title":"J R Coll Surg Edinb"},{"key":"bibr7-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1007\/1-4020-2586-6_33"},{"key":"bibr8-0960327119829521","first-page":"465","volume":"22","author":"Orororo OC","year":"2018","journal-title":"J Appl Sci Environ Manage"},{"key":"bibr9-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.08.007"},{"key":"bibr10-0960327119829521","first-page":"443","volume-title":"The liver: biology and pathobiology","author":"Inoue M","year":"2011","edition":"5"},{"key":"bibr11-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2018.02.003"},{"key":"bibr12-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-014-1302-y"},{"key":"bibr13-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.03.008"},{"key":"bibr14-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2018.03.009"},{"key":"bibr15-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(00)00199-X"},{"key":"bibr16-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101053200"},{"key":"bibr17-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-007-9279-9"},{"key":"bibr18-0960327119829521","first-page":"1223","volume":"24","author":"Chiu MM","year":"2009","journal-title":"Histol Histopathol"},{"key":"bibr19-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-12-92"},{"key":"bibr20-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.05.049"},{"key":"bibr21-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-015-0453-x"},{"key":"bibr22-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2014-0114"},{"key":"bibr23-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2016.1236425"},{"key":"bibr24-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2005.41.10.920428"},{"key":"bibr25-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002907"},{"key":"bibr26-0960327119829521","first-page":"479","volume-title":"Tietz Textbook of Clinical Chemistry and Molecular Diagnostics","author":"Lamb EJ","year":"2018","edition":"6"},{"key":"bibr27-0960327119829521","volume-title":"Textbook of clinical chemistry","author":"Tietz N","year":"1986"},{"key":"bibr28-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)86134-H"},{"key":"bibr29-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1159\/000136485"},{"key":"bibr30-0960327119829521","first-page":"243","volume-title":"Handbook of methods for oxygen radical research","author":"Marklund SL","year":"1985"},{"key":"bibr31-0960327119829521","first-page":"283","volume-title":"Handbook of methods of oxygen radical research","author":"Caliborne AL","year":"1985"},{"key":"bibr32-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2013.01.024"},{"key":"bibr33-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"bibr34-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr031"},{"key":"bibr35-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(00)00210-9"},{"key":"bibr36-0960327119829521","first-page":"456","volume":"7","author":"Patrick L","year":"2002","journal-title":"Altern Med Rev"},{"key":"bibr37-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2004.05.001"},{"key":"bibr38-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020229923095"},{"key":"bibr39-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.02.007"},{"key":"bibr40-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.03.010"},{"key":"bibr41-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2006.07.012"},{"key":"bibr42-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.01.002"},{"key":"bibr43-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2006.04.004"},{"key":"bibr44-0960327119829521","first-page":"41","volume":"49","author":"Kawamoto S","year":"2007","journal-title":"Nihon Jinzo Gakkai Shi"},{"key":"bibr45-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2005.08.006"},{"key":"bibr46-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1159\/000070241"},{"key":"bibr47-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07913.x"},{"key":"bibr48-0960327119829521","first-page":"177","volume":"88","author":"Kamiyama T","year":"1995","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"bibr49-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04560.x"},{"key":"bibr50-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2009.03.010"},{"key":"bibr51-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfj131"},{"key":"bibr52-0960327119829521","first-page":"2905","volume":"7","author":"Yuan G","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"bibr53-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-016-7953-x"},{"key":"bibr54-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.suppl_2.35"},{"key":"bibr55-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(02)00595-4"},{"key":"bibr56-0960327119829521","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2008.00041.x"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327119829521","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0960327119829521","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327119829521","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:48:45Z","timestamp":1777448925000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0960327119829521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,11]]},"references-count":56,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1177\/0960327119829521"],"URL":"https:\/\/doi.org\/10.1177\/0960327119829521","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,11]]}}}