An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management.

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.

Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity - possible modulatory role of IL-11.

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

Análise de metabólitos secundários presentes nas plantas Cynara scolymus L e Artemisia absinthium L durante o tratamento de dislipidemias / Analysis of secondary metabolites present in the plants Cynara scolymus L and Artemisia absinthium L during the treatment of dyslipidemia

O uso de plantas medicinais como forma de tratamento para várias doenças é uma tradição que se estende entre gerações, há milhares de anos. Os povos antigos costumavam usar partes específicas de alguns vegetais para a realização de chás e curativos para feridas. Ainda nos dias atuais, muitas pessoas preferem as formas naturais como tratamento para suas comorbidades, principalmente como adjuvantes no combate às dislipidemias. O presente trabalho teve o objetivo de analisar as plantas Cynara scolymus L e Artemisia absinthium L para confirmar a presença ou ausência de proteases específicas contra a hipercolesterolemia. A pesquisa foi realizada através de uma triagem das plantas no software RCSB (https://www.rcsb.org/). No final, pode-se confirmar que a planta Cynara scolymus L atende às perspectivas de tratamento da hipercolesterolemia, enquanto a Artemisia absinthium L não apresentou valores suficientes que sejam eficazes no tratamento.

The use of medicinal plants as a form of treatment for various diseases is a tradition that has spanned generations for thousands of years. Ancient people used to use specific parts of some vegetables to make teas and dressings for wounds. Even today, many people prefer natural forms as a treatment for their comorbidities, especially as adjuvants in the fight against dyslipidemia. The present work aimed to analyze the plants Cynara scolymus L and Artemisia absinthium L to confirm the presence or absence of specific proteases against hypercholesterolemia. The research was carried out by screening the plants using the RCSB software (https://www.rcsb.org/). In the end, it can be confirmed that the Cynara scolymus L plant meets the prospects for treating hypercholesterolemia, while Artemisia absinthium L did not present sufficient values that are effective in the treatment.