顺铂(CDDP)通常会导致肾脏损害,限制其在癌症治疗中的有效性。近端小管中线粒体自噬的缺乏加剧了这个问题。因此,靶向SIRT-3和PGC1-α有望减轻CDDP诱导的肾损伤。利格列汀的潜在肾脏保护作用,然而,仍然知之甚少。本研究首次探索了利格列汀对CDDP诱导的大鼠肾脏损害的影响。强调其在有丝分裂途径中的潜在作用。实验涉及四个大鼠组:组(I)仅接受生理盐水,组(II)接受单次腹膜内注射6mg/kg的CDDP。组(III)和(IV)接受6和10mg/kgp.o.利格列汀,分别,CDDP管理前七天,再继续四天。各种参数,包括肾功能测试,氧化应激,TNF-α,IL-1β,IL-6,PGC-1α,FOXO-3a,p-ERK1,SIRT-3和P62基因在肾组织中的表达,被评估。利格列汀改善肾功能,增加抗氧化酶活性,IL-1β减少,TNF-α,和IL-6表达。此外,利格列汀显著上调PGC-1α和PINK-1/Parkin-2表达,同时下调P62表达。此外,利格列汀激活FOXO-3a和SIRT-3,提示线粒体自噬的潜在增强。利格列汀在CDDP诱导的损害中对与肾脏健康相关的各种因素具有积极影响。这些研究结果表明,利格列汀在改善癌症治疗结果方面具有潜在作用。临床试验有必要进一步研究和验证其在临床环境中的疗效。
Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of
linagliptin, however, remain poorly understood. This study represents the first exploration of
linagliptin\'s impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received
linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1β, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1β, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover,
linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for
linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.