The modulation of sirtuins by natural compounds in the management of cisplatin-induced nephrotoxicity.

Cisplatin is a highly effective antitumor agent. However, its use is limited due to severe adverse effects, particularly nephrotoxicity, which occurs in approximately 30% of patients. There is a need for novel renoprotective compounds. Sirtuins play a vital role in various physiological and pathological processes such as oxidative stress, apoptosis, inflammation, and mitochondrial bioenergetics. It has been shown that sirtuins can exert a protective effect on cisplatin-induced acute kidney injury by targeting multiple signaling pathways. Besides, sirtuins not only did not reduce the anticancer effect of cisplatin but also increased it. Several natural compounds have been reported to inhibit cisplatin-mediated nephrotoxicity through sirtuin stimulation. These compounds exert their therapeutic effects on cisplatin-induced renal injury by targeting various signaling pathways including Sirt1/p53, Sirt1/NF-κb/p56, AMPK/Sirt1, Sirt1/PGC-1α, and/or by enhancing mitochondrial function.

Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters. METHODS: The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle-Ottawa Scale score. RESULTS: Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression. CONCLUSION: Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.

Inhibition of Interleukin-1 in the Treatment of Selected Cardiovascular Complications.

BACKGROUND: Interleukin-1 (IL-1) is a pro-inflammatory cytokine that is produced by endothelial cells, smooth muscle cells, and macrophages. It is an important regulator of a complex humoral and cellular inflammatory response. IL-1ß is known to be implicated in the development of chronic inflammatory disorders such as rheumatoid arthritis. We aimed to review the effects of IL-1ß antagonists in various cardiovascular disorders and to discuss their effectiveness in such diseases. METHODS: Major biomedical databases, including PubMed and Scopus, were searched for clinical studies regarding the treatment of cardiovascular diseases (CVD) using IL-1ß antagonists. RESULTS: The drugs currently used in clinical trials are anakinra, the monoclonal antibodies canakinumab and gevokizumab, and the soluble decoy receptor rilonacept. There are clinical trials and case reports of patients with CVD in which anakinra administration, at the standard dose, has caused rapid clinical improvement and recovery in a few months. Our comprehensive search revealed that IL-1ß antagonists have beneficial effects in the treatment of various cardiovascular disorders such as myocarditis, pericarditis, heart failure, acute coronary syndrome, myocardial infarction, atherosclerosis, and Kawasaki disease. CONCLUSION: The present review article shows that IL-1ß has a major role in the pathophysiology of cardiovascular disorders, its antagonists have beneficial effects in these conditions, and their use should be considered in future studies.