PMID- 38115227 OWN - NLM STAT- MEDLINE DCOM- 20240422 LR - 20240422 IS - 1537-6524 (Electronic) IS - 1537-6516 (Linking) VI - 34 IP - 4 DP - 2024 May TI - Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis. PG - 413-422 LID - 10.1080/15376516.2023.2297234 [doi] AB - Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1beta), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-alpha (TNF-alpha), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1beta, iNOS, TNF-alpha, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity. FAU - Akcakavak, Gokhan AU - Akcakavak G AUID- ORCID: 0000-0001-5949-4752 AD - Department of Pathology, Yozgat Bozok University, Yozgat, Turkey. FAU - Kazak, Filiz AU - Kazak F AUID- ORCID: 0000-0002-9065-394X AD - Department of Biochemistry, Hatay Mustafa Kemal University, Hatay, Turkey. FAU - Karatas, Ozhan AU - Karatas O AUID- ORCID: 0000-0002-2778-8059 AD - Department of Pathology, Cumhuriyet University, Sivas, Turkey. FAU - Alakus, Halil AU - Alakus H AUID- ORCID: 0000-0001-9265-2310 AD - Department of Surgery Hatay Mustafa Kemal University, Hatay, Turkey. FAU - Alakus, Ibrahim AU - Alakus I AUID- ORCID: 0000-0002-2031-7035 AD - Department of Surgery Hatay Mustafa Kemal University, Hatay, Turkey. FAU - Kirgiz, Omer AU - Kirgiz O AUID- ORCID: 0000-0002-0222-1363 AD - Department of Surgery Hatay Mustafa Kemal University, Hatay, Turkey. FAU - Celik, Zeynep AU - Celik Z AUID- ORCID: 0000-0002-9667-5728 AD - Department of Pathology, Selcuk University, Konya, Turkey. FAU - Yilmaz Deveci, Mehmet Zeki AU - Yilmaz Deveci MZ AUID- ORCID: 0000-0002-9532-247X AD - Department of Surgery Hatay Mustafa Kemal University, Hatay, Turkey. FAU - Ozdemir, Ozgur AU - Ozdemir O AUID- ORCID: 0000-0002-1595-0557 AD - Department of Pathology, Selcuk University, Konya, Turkey. FAU - Tuzcu, Mehmet AU - Tuzcu M AUID- ORCID: 0000-0003-3118-1054 AD - Department of Pathology, Selcuk University, Konya, Turkey. LA - eng PT - Journal Article DEP - 20231226 PL - England TA - Toxicol Mech Methods JT - Toxicology mechanisms and methods JID - 101134521 RN - 0 (NF-kappa B) RN - 0 (Gentamicins) RN - RV6J6604TK (Eucalyptol) RN - EC 3.4.22.- (Caspase 3) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Antioxidants) RN - 0 (Anti-Inflammatory Agents) SB - IM MH - Rats MH - Animals MH - *NF-kappa B/metabolism MH - *Gentamicins/toxicity MH - Eucalyptol/metabolism/pharmacology/therapeutic use MH - Caspase 3/metabolism MH - NF-E2-Related Factor 2/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Kidney MH - Oxidative Stress MH - Antioxidants/metabolism MH - Inflammation/metabolism MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Apoptosis OTO - NOTNLM OT - Gentamicin OT - apoptosis OT - eucalyptol OT - inflammation OT - nephrotoxicity OT - oxidative stress EDAT- 2023/12/20 06:42 MHDA- 2024/04/22 06:42 CRDT- 2023/12/20 00:42 PHST- 2024/04/22 06:42 [medline] PHST- 2023/12/20 06:42 [pubmed] PHST- 2023/12/20 00:42 [entrez] AID - 10.1080/15376516.2023.2297234 [doi] PST - ppublish SO - Toxicol Mech Methods. 2024 May;34(4):413-422. doi: 10.1080/15376516.2023.2297234. Epub 2023 Dec 26.