Agri Ibrahim Cecen University, Faculty of Pharmacy, Department of Biochemistry, Agri, Turkey.
Ataturk University, Faculty of Pharmacy, Department of Pharmacology, Erzurum, Turkey.
Life Sci. 2021 Feb 1;266:118869. doi: 10.1016/j.lfs.2020.118869. Epub 2020 Dec 9.
Cisplatin (Cis) is widely used chemotherapeutic and has some serious side effects as nephrotoxicity. Phloretin (PH) and Phloridzin (PZ) are known their anti-oxidant anti-inflammatory effects. We aimed to examine the protective effects of PH and PZ on cisplatin-induced nephrotoxicity.
Totally, 48 Balb/C female mice were separated into eight groups (n = 6). First day, single dose of cisplatin (20 mg/kg intraperitoneal) was administered to induce toxicity. PH and PZ were given (50 and 100 mg/kg orally) to treatment groups during 3 days. After the experimental procedures serum renal function enzymes (BUN and Creatinine), oxidative parameters (SOD, GSH and MDA), nuclear agent NFKβ, inflammatory cytokines (Tnf-α and IL1β) and HSP70 expressions and histopathological assessments were analyzed.
Serum enzymes, tissue cytokines and oxidative stress were increased after the Cis treatment. PH and PZ treatments normalized all parameters compared to Cis administrated group. After the treatments, SOD activities and GSH levels were increased while MDA levels were decreased. PH and PZ treatments decreased Tnf-α, IL1β and NFKβ mRNA expressions. Cis significantly increased the HSP70 expression while PH and PZ administrations significantly decreased. Similar the biochemical and molecular results, PH and PZ showed positive effects on tissue pathological parameters. Cisplatin cause a lot of abnormal structures as tubular and glomeruli damages on the kidney.
PH and PZ play important physiological roles in the prevention of nephrotoxicity. Antioxidant and anti-inflammatory effects of PH and PZ demonstrated visible protective effects in the cisplatin-induced nephrotoxicity model.
顺铂（Cis）被广泛用作化疗药物，但其具有肾毒性等严重的副作用。根皮苷（PH）和根皮素（PZ）具有抗氧化和抗炎作用。本研究旨在探讨 PH 和 PZ 对顺铂诱导的肾毒性的保护作用。
将 48 只雌性 Balb/C 小鼠分为 8 组（n=6）。第一天，给予单剂量顺铂（20mg/kg 腹腔注射）诱导毒性。在 3 天内，通过口服给予 PH 和 PZ（50 和 100mg/kg）进行治疗。实验程序结束后，分析血清肾功能酶（BUN 和肌酐）、氧化参数（SOD、GSH 和 MDA）、核因子 NFKβ、炎症细胞因子（TNF-α 和 IL1β）和 HSP70 的表达以及组织病理学评估。
顺铂处理后，血清酶、组织细胞因子和氧化应激增加。与顺铂给药组相比，PH 和 PZ 治疗使所有参数正常化。治疗后，SOD 活性和 GSH 水平增加，MDA 水平降低。PH 和 PZ 治疗降低了 TNF-α、IL1β 和 NFKβ 的 mRNA 表达。顺铂显著增加 HSP70 的表达，而 PH 和 PZ 的给药显著降低。与生化和分子结果相似，PH 和 PZ 对组织病理参数显示出积极的影响。顺铂导致肾脏的管状和肾小球损伤等大量异常结构。
PH 和 PZ 在预防肾毒性方面发挥着重要的生理作用。PH 和 PZ 的抗氧化和抗炎作用在顺铂诱导的肾毒性模型中显示出明显的保护作用。
