{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:13:03Z","timestamp":1790885583524,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["PNURSP2023R171"],"award-info":[{"award-number":["PNURSP2023R171"]}]},{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["R.G.P.1\/167\/43"],"award-info":[{"award-number":["R.G.P.1\/167\/43"]}]},{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["PNURSP2023R171"],"award-info":[{"award-number":["PNURSP2023R171"]}]},{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["R.G.P.1\/167\/43"],"award-info":[{"award-number":["R.G.P.1\/167\/43"]}]},{"name":"Research Deanship of King Khalid University, Abha, Saudi Arabia","award":["PNURSP2023R171"],"award-info":[{"award-number":["PNURSP2023R171"]}]},{"name":"Research Deanship of King Khalid University, Abha, Saudi Arabia","award":["R.G.P.1\/167\/43"],"award-info":[{"award-number":["R.G.P.1\/167\/43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg\/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks. The control rats were injected with the vehicle for the same period. The metformin-treated group received 200 mg\/kg metformin daily for 10 weeks, beginning week 1, and received TAA injections with dosage and timing similar to those of the model group. All rats were culled at week 10. It was observed that TAA induced substantial renal injury, as demonstrated by significant kidney tissue damage and fibrosis, as well as augmented blood and kidney tissue levels of urea, creatinine, inflammation, oxidative stress, dyslipidemia, tissue inhibitor of metalloproteinases-1 (TIMP-1), and hypertension. TAA nephrotoxicity substantially inhibited the renal expression of phosphorylated AMPK. All these markers were significantly protected by metformin administration. In addition, a link between kidney fibrosis and these parameters was observed. Thus, metformin provides profound protection against TAA-induced kidney damage and fibrosis associated with the augmentation of the tissue protective enzyme AMPK and inhibition of oxidative stress, inflammation, the profibrogenic gene TIMP-1, dyslipidemia, and hypertension for a period of 10 weeks in rats.<\/jats:p>","DOI":"10.3390\/molecules28062756","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:30:31Z","timestamp":1679283031000},"page":"2756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7096-0221","authenticated-orcid":false,"given":"Mohammad Y.","family":"Alshahrani","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61413, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-9649","authenticated-orcid":false,"given":"Hasnaa A.","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed M.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nervana M.","family":"Bayoumy","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaa S.","family":"Kamar","sequence":"additional","affiliation":[{"name":"Department of Histology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"},{"name":"Histology Department, Armed Forces College of Medicine, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-0818","authenticated-orcid":false,"given":"Asmaa M.","family":"ShamsEldeen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0990-8093","authenticated-orcid":false,"given":"Mohamed A.","family":"Haidara","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5773-1160","authenticated-orcid":false,"given":"Bahjat","family":"Al-Ani","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-3891","authenticated-orcid":false,"given":"Alia","family":"Albawardi","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,18]]},"reference":[{"key":"ref_1","first-page":"113","article-title":"Molecular interactions with mercury in the kidney","volume":"52","author":"Zalups","year":"2000","journal-title":"Pharmacol. 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