Kazmi Imran, Al-Abbasi Fahad A, Afzal Muhammad, Nadeem Muhammad Shahid, Altayb Hisham N, Gupta Gaurav
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmacology, College of Pharmacy, Jouf University, Sakakah 72341, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Jul 20;15(7):899. doi: 10.3390/ph15070899.
Severe infections such as viral, bacterial, or fungal sepsis can cause an inflammatory response in the host, leading to organ failure and septic shock-phosphodiesterase-4 (PDE-4) inhibiting related agents from suppressing cyclic adenosine monophosphate (cAMP) degradation. Regulatory organisations have approved some substances in this category to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with chronic bronchitis and a history of COPD exacerbations. Roflumilast has been shown to alleviate inflammatory responses, thus regulating airway inflammation. Additionally, roflumilast therapy dramatically enhanced B-cell lymphoma 2 (Bcl-2) expression, an anti-apoptotic marker lowered in septic animals. Previous research has indicated that roflumilast may help reverse sepsis-induced liver and lung harm, but whether it is also effective in reversing sepsis-induced renal impairment remains unknown. Therefore, this review determines whether roflumilast protects against renal dysfunction, inflammatory response, and apoptosis in sepsis-induced kidney damage. Additionally, we discussed the molecular mechanism through which roflumilast exerts its protective effect to uncover a possible treatment agent for sepsis-induced renal impairment.
严重感染，如病毒、细菌或真菌性脓毒症，可在宿主体内引发炎症反应，导致器官衰竭和感染性休克。磷酸二酯酶-4（PDE-4）抑制相关药物可抑制环磷酸腺苷（cAMP）降解。监管机构已批准该类别中的一些物质，以降低慢性支气管炎且有慢性阻塞性肺疾病（COPD）加重病史患者发生COPD加重的风险。罗氟司特已被证明可减轻炎症反应，从而调节气道炎症。此外，罗氟司特治疗显著提高了B细胞淋巴瘤2（Bcl-2）的表达，Bcl-2是脓毒症动物体内降低的一种抗凋亡标志物。先前的研究表明，罗氟司特可能有助于逆转脓毒症引起的肝肺损伤，但它是否也能有效逆转脓毒症引起的肾功能损害尚不清楚。因此，本综述确定罗氟司特是否能预防脓毒症诱导的肾损伤中的肾功能障碍、炎症反应和细胞凋亡。此外，我们还讨论了罗氟司特发挥保护作用的分子机制，以发现一种可能治疗脓毒症诱导的肾功能损害的药物。
