Cisplatin (CP), an effective chemotherapeutic agent, is known to cause cardiotoxicity, limiting its clinical application. This study aimed to investigate the potential cardioprotective effects of linagliptin (LG) against cisplatin-induced cardiac injury and to elucidate its underlying mechanisms. There were four groups of male Wistar rats: control, cisplatin (CP, 8 mg/kg, IP), and two groups with LG treatment (5 mg/kg and 10 mg/kg, orally) and CP. CP significantly increased cardiac injury markers (CK, CK-MB, TNNC1) and oxidative stress (decreased SOD and GSH, increased MDA) compared to controls (p < 0.05). It also elevated inflammatory cytokines (TNF-α, IL-6) and disrupted mitochondrial function (altered ATP level and NADP/NADPH ratios). Furthermore, CP decreased the expression of SIRT1 and Nrf2 and the level of p-AMPK. LG treatment dose-dependently attenuated these changes, with the 10 mg/kg dose showing greater efficacy. Histopathological examination and immunohistochemistry confirmed these biochemical findings, showing improved cardiac structure and increased expression of SIRT1 and Nrf2 with LG treatment. Linagliptin demonstrates potent cardioprotective effects against cisplatin-induced toxicity, primarily through modulation of the SIRT1/AMPK/Nrf2 signaling pathway, thereby resulting in reduced oxidative stress and inflammation. These findings suggest that linagliptin may serve as a potential adjuvant therapy to mitigate cisplatin-induced cardiotoxicity.
Mahdi H Alsugoor, Naif Al Suhaymi, Bassim M S A Mohamed et al.· Drug and chemical toxicology...· 0 citations
Cisplatin (Cis), a commonly used chemotherapy drug, is associated with liver toxicity, which restricts its broader clinical use. This study investigated the potential protective effects of linagliptin (Lina), a DPP‐4 inhibitor, in preventing liver damage induced by Cis in rats. There were four groups of male rats: a control group, a Cis group (8 mg/kg, IP), and cotreated groups given Lina (5 and 10 mg/kg, orally) with Cis. Lina was administered daily for 15 days, with Cis injected on Day 8. Liver function, oxidative stress markers, inflammatory mediators, energy metabolism indicators, and key signaling proteins were assessed. Cis administration resulted in significant hepatotoxicity, evidenced by elevated liver enzymes, increased oxidative stress, enhanced inflammatory response, and disrupted energy metabolism. Lina treatment, particularly at the 10‐mg/kg dose, demonstrated marked hepatoprotective effects. It significantly reduced liver enzyme levels, improved antioxidant status, attenuated inflammatory markers, and restored energy metabolism indicators. Moreover, Lina positively modulated essential signaling proteins involved in cellular stress response and metabolism, including signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta 1 (TGF‐β), silent information regulator 1 (SIRT1), and peroxisome proliferator–activated receptor gamma coactivator 1‐alpha (PGC‐1α). The results indicate that Lina protects against Cis‐induced liver damage by leveraging its antioxidant, anti‐inflammatory, and metabolic regulation properties. This study offers new insights into potential strategies for mitigating Cis‐induced hepatotoxicity and enhancing its therapeutic index in cancer treatment.
M. A. Elbaset, Bassim M S A Mohamed, Passant E. Moustafa et al.· Advances in pharmacological...· 0 citations
