Unver, Edhem; Tosun, Mustafa; Olmez, Hasan; Kuzucu, Mehmet; Cimen, Ferda Keskin; Suleyman, Zeynep; Xiao, Cheng

The effect of taxifolin on cisplatin-induced oxidative pulmonary damage was investigated biochemically and histopathologically in male albino Wistar rats. There were four groups, with six animals in each group: 50 mg/kg of taxifolin plus 2.5 mg/kg of cisplatin (TC) group, 2.5 mg/kg of cisplatin only (CIS) group, 50 mg/kg of taxifolin only (TG) group, and a healthy control group (HG). In terms of the experimental procedure, the animals in the TC and TG groups were first treated via oral gavage. The CIS and HG groups received distilled water as solvent, respectively. One hour later, the TC and CIS groups received cisplatin at a dose of 2.5 mg/kg (injected intraperitoneally). Taxifolin, cisplatin, and the distilled water were administered at the indicated dose and volume, using the same method daily for 14 d. At the end of this period, the animals were killed with a high dosage of thiopental anaesthesia (50 mg/kg). Blood and lung tissue samples were taken for biochemical (malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), and 8-hydroxy-2 deoxyguanosine (8-OHdG)) analyses and histopathological examinations. The biochemical and histopathological results in the TC and HG groups were then compared with those in the CIS group. Cisplatin increased the levels of MDA, myeloperoxidase, and 8-OHdG, a marker of oxidative DNA damage, and reduced the amount of tGSH in the lung tissue. Moreover, severe alveolar damage, including oedema and extensive alveolar septal fibrosis, in addition to infiltration of polymorphic nuclear leucocytes and haemorrhagic foci, was observed in the CIS group. These histopathological findings demonstrate that taxifolin provides protection against pulmonary oxidative stress by preventing increases in oxidant parameters and decreases in antioxidants.

Onk, Didem; Onk, Oruc Alper; Turkmen, Kultigin; Erol, Huseyin Serkan; Ayazoglu, Tulin Akarsu; Keles, Osman Nuri; Halici, Mesut; Topal, Ergun

Background. Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p<0.05). Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.