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.

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-1ß), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), 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-1ß, iNOS, TNF-α, 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.

Investigation of the effects of safranal on the experimentally created rheumatoid arthritis model in rats.

Rheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-α, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.