{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:08:18Z","timestamp":1771240098701,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine pyrophosphate (TPP) remain poorly defined. This study aimed to evaluate whether ATP and TPP mitigate metformin-induced renal injury through biochemical and histopathological assessments. Wistar rats were randomly divided into six groups: control, ATP, TPP, metformin, ATP + metformin, and TPP + metformin. Metformin (50 mg\/kg, oral), ATP (4 mg\/kg, intraperitoneal), or TPP (20 mg\/kg, intraperitoneal) was administered daily for 10 days. Oxidative stress markers, inflammatory cytokines, renal histopathology, and serum creatinine, BUN, lactate, and LDH levels were evaluated. Metformin induced significant oxidative stress, inflammation, metabolic disturbance, and renal injury. ATP provided partial protection, whereas TPP markedly restored redox balance, reduced inflammation, and preserved renal histology. TPP confers superior protection against metformin-induced renal injury compared with ATP by modulating oxidative, inflammatory, and metabolic pathways, highlighting its therapeutic potential in preventing metformin-related nephrotoxicity.<\/jats:p>","DOI":"10.3390\/ijms27041825","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Protective Strategy Against Metformin-Induced Renal Injury Involving Adenosine Triphosphate and Thiamine Pyrophosphate"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-7692","authenticated-orcid":false,"given":"Huseyin","family":"Kocaturk","sequence":"first","affiliation":[{"name":"Department of Urology, Erzurum City Hospital, University of Health Sciences, Erzurum 25240, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fevzi","family":"Bedir","sequence":"additional","affiliation":[{"name":"Department of Urology, Erzurum City Hospital, University of Health Sciences, Erzurum 25240, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-0678","authenticated-orcid":false,"given":"Bulent","family":"Yavuzer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3491-9798","authenticated-orcid":false,"given":"Esra Tuba","family":"Sezgin","sequence":"additional","affiliation":[{"name":"Anesthesia Program, Vocational School of Health Services, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24036, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renad","family":"Mammadov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahadir","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-5502","authenticated-orcid":false,"given":"Cengiz","family":"Sarigul","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferda Keskin","family":"Cimen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-0666","authenticated-orcid":false,"given":"Mehmet Sefa","family":"Altay","sequence":"additional","affiliation":[{"name":"Department of Urology, Erzurum City Hospital, University of Health Sciences, Erzurum 25240, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-4099","authenticated-orcid":false,"given":"Halis","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, Erzincan 24100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0889-8529(05)70265-6","article-title":"Metformin","volume":"26","author":"Bell","year":"1997","journal-title":"Endocrinol. 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