Search Results (52)

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate the efficacy and safety of novel oral anti-cholestatic agents for PBC. Methods: A systematic literature search was conducted in electronic databases up to September 2024. Randomized controlled trials, cohort studies, and case-control studies evaluating novel oral anti-cholestatic agents in adult PBC patients were included. The primary outcome was a change in alkaline phosphatase (ALP) levels. Safety was assessed by the incidence of serious adverse events. Random-effect meta-analyses were performed. Results: Ten studies involving 878 patients were analyzed. Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. The meta-analysis showed significant reductions in ALP levels with novel agents compared to the controls (SMD −2.80; 95% CI −3.56, −2.03; p < 0.00001), with high heterogeneity (I² = 93%). Saroglitazar achieved the largest effect size. There was no significant difference in serious adverse events between novel agents and controls (OR 1.21; 95% CI 0.81, 1.83; p = 0.35). Conclusions: Novel oral anti-cholestatic agents show promise in improving biochemical markers in PBC patients with suboptimal UDCA responses, with a safety profile comparable to controls. However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety. Full article

Nature-based solutions represent a decentralized wastewater treatment proposal, offering diverse mechanisms for effectively removing emerging contaminants, particularly acidic pharmaceuticals. This study evaluated the performance of acidic-drug (diclofenac, fenofibrate, ibuprofen, gemfibrozil, fenoprofen, naproxen, and indomethacin) removal from wastewater using a surface-flow constructed wetland with an organic bed (Eichhornia crassipes (Mart.) Solms, 18 ind/m²), and a horizontal subsurface-flow constructed wetland, divided into three sections. The process was complemented by two stabilization ponds and other horizontal subsurface-flow wetlands using papyrus (Cyperus papyrus L., 8–13 ind/m²) and tezontle as support media. The industrial-scale system (67.8 m²) was fed with wastewater at a rate of 1.33 m³/d with a hydraulic time retention of about 5.8 days. Drugs were quantified by gas chromatography. The results showed that gemfibrozil and indomethacin were completely removed (100%), while diclofenac (73%) and naproxen (94%) showed significant removals. Fenoprofen was not removed. Ibuprofen and fenofibrate showed increased concentrations, resulting in negative removals due to anoxic conditions (ibuprofen) and a slightly neutral pH (fenofibrate). These findings underscore the system’s ability to improve water quality by removing most acidic drugs, suggesting that the hybrid design is particularly effective in treating specific wastewater contaminants. Full article

Background: Hypertriglyceridemia has serious health risks such as cardiovascular disease, type 2 diabetes mellitus, nephropathy, and others. Fenofibrate is an effective hypolipidemic drug, but its benefits for ameliorating disorders associated with hypertriglyceridemia failed to be proven in clinical trials. Methods: To search for possible causes of this situation and possibilities of their favorable influence, we tested the effect of FF monotherapy and the combination of fenofibrate with silymarin on metabolic disorders in a unique model of hereditary hypertriglyceridemic rats (HHTg). Results: Fenofibrate treatment (100 mg/kg BW/day for four weeks) significantly decreased serum levels of triglyceride, (−77%) and free fatty acids (−29%), the hepatic accumulation of triglycerides, and the expression of genes encoding transcription factors involved in lipid metabolism (Srebf2, Nr1h4. Rxrα, and Slco1a1). In contrast, the hypertriglyceridemia-induced ectopic storage of lipids in muscles, the heart, and kidneys reduced glucose utilization in muscles and was not affected. In addition, fenofibrate reduced the activity of the antioxidant system, including Nrf2 expression (−35%) and increased lipoperoxidation in the liver and, to a lesser extent, in the kidneys and heart. Adding silymarin (micronized form, 600 mg/kg BW/day) to fenofibrate therapy increased the synthesis of glycogen in muscles, (+36%) and reduced hyperinsulinemia (−34%). In the liver, it increased the activity of the antioxidant system, including PON-1 activity and Nrf2 expression, and reduced the formation of lipoperoxides. The beneficial effect of combination therapy on the parameters of oxidative stress and lipoperoxidation was also observed, to a lesser extent, in the heart and kidneys. Conclusions: Our results suggest the potential beneficial use of the combination of FF with SLM in the treatment of hypertriglyceridemia-induced metabolic disorders. Full article

Background/Objectives: Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic disease of the liver that symptomatically can present with pruritus and fatigue. Its established first- and second-line therapies are ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) although they provide limited symptom management. Liver transplantation offers a potentially curative therapeutic option in refractory cases progressing to cirrhosis. Novel research published after the current guidelines highlights the importance of providing an up-to-date analysis of treatment options available. Methods: In this study, we conducted a literature search using Pubmed, Ovid Medline, and SCOPUS to provide a narrative review of first-line, second-line, and emerging therapies in PBC. Results: UDCA has been well established as a long-term, safe therapy within the literature although it is possible that treatment dosage can be further optimised in refractory patients. It has a favourable side effect profile. Despite improving biochemical markers, histopathological profile, and overall outcomes, up to 30–40% of patients are refractory to it. Age and sex are highlighted as independent indicators of non-responsiveness. This necessitates effective second-line therapies. Future trials could aim to investigate UDCA as a co-first-line therapy. Further supporting results for OCA were found in the interim extension trial of the seminal POISE study. The long-term phase 4 COBOLT trial is still awaiting results to further assess the complications, adherence, and potential adverse effects. It is a viable option in UDCA-refractory patients. The high incidence rate of dose-related pruritis indicates that alternative second-line options are needed. Bezafibrate is an off-label antilipemic agent that shows promise as a prospective second-line therapy option. The landmark BEZURSO trial alleviated some efficacy and safety concerns, but it remains associated with elevated serum creatinine; thus, it should be considered with caution. Other prospective second-line therapies are budesonide, triple therapy, and novel agents such as seladelpar and elafibranor. Conclusions: UDCA should remain the treatment of choice for PBC, though perhaps not as monotherapy. With further investigation, BF shows promise as a new second-line therapy alongside OCA, which it may outperform. Full article

Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg⁻¹ or fenofibrate at 4 mg·kg⁻¹. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues. Full article

Hyperlipidemia is the root cause of numerous chronic conditions, leading to high mortality rates around the globe. Spirulina (Arthrospira platensis) microalgae serve as a promising reservoir of bioactive compounds with diverse pharmacological properties. The current study examined the nutritional profile of spirulina powder in relation to strict glycemic control, specifically focusing on its potential to lower lipid levels. In an in vivo investigation, normal healthy male Wistar albino rats (n = 60) were divided into two groups: a negative control group (NC) of ten rats and a high-fat diet group (n = 50) that were fed a cholesterol-rich diet until their cholesterol levels reached or exceeded 250 mg/dL. Subsequently, the hypercholesterolemic rats were then randomly allocated to several treatment groups: a positive control (PC); a standard treatment diet (STD) involving fenofibrate at a dose of 20 mg/kg body weight; and three experimental groups (T1, T2, and T3) that received spirulina powder supplementation at doses of 300, 600, and 900 mg per kg body weight, respectively, for the period of 12 weeks. Blood samples were analyzed for oxidative stress biomarkers, insulin levels, lipid profiles, liver function, and expression of gene levels in the diabetogenic pathway. The study utilized spectrophotometric colorimetric methods to identify oxidative stress biomarkers, serum kit methods to measure lipid profiles and liver enzymes, and the assessment of qPCR for mRNA quantity. According to the research findings, spirulina powder has certain noteworthy features. It had the greatest quantity of chlorogenic acid (4052.90 µg/g) among seven phenolics and two flavonoid compounds obtained by HPLC-UV analysis. Furthermore, the proximate analysis demonstrated that spirulina is high in protein (16.45 ± 0.8%) and has a significant energy yield of 269.51 K-calories per 100 g. A maximal spirulina dose of 900 mg/kg/wt significantly lowered oxidative stress, cholesterol, triglyceride, low-density lipoproteins (LDL), and insulin levels (p ≤ 0.05). In contrast, high-density lipoprotein (HDL) and total antioxidant capacity (TAC) levels increased significantly (p ≤ 0.05) compared to all other groups, except the NC group. The study provides remarkable proof about the pharmacological impact of spirulina powders. Significant reductions (p ≤ 0.05) in liver enzymes {alanine aminotransferase (ALT) and aspartate aminotransferase (AST)} were observed across all treatment groups, with the exception of the NC, compared to the positive control. The treatment groups had significantly greater gene expression levels of INS-1, PDX-1, IGF-1, and GLUT-2 than the positive control group (p ≤ 0.05). These findings highlight spirulina’s potential as a long-term regulator of hyperglycemia in rat models with induced hyperlipidemia, owing to its phenolic bioactive components that serve as antioxidants. Full article

Background: (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, has significant anti-adipogenesis potential; it regulates adipogenic transcription factors. However, whether HMC improves hepatic steatosis in hepatocytes remains vague. This study investigated whether HMC ameliorates hepatic steatosis in free fatty acid-treated human hepatocellular carcinoma (HepG2) cells, and if so, its mechanism of action was analyzed. Methods: Hepatic steatosis was induced by a free fatty acid mixture in HepG2 cells. Thereafter, different HMC concentrations (10, 30, and 50 µM) or fenofibrate (10 µM, a PPARα agonist, positive control) was treated in HepG2 cells.Results: HMC markedly decreased lipid accumulation and triglyceride content in free fatty acid-treated HepG2 cell; it (10 and 50 μM) markedly upregulated protein expressions of pAMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. HMC (10 and 50 μM) markedly inhibited the expression of sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl-coA desaturase 1, which are the enzymes involved in lipid synthesis. Furthermore, HMC (10 and 50 μM) markedly upregulated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) and enhanced the protein expressions of carnitine palmitoyl transferase 1 and acyl-CoA oxidase 1. Conclusion: HMC inhibits lipid accumulation and promotes fatty acid oxidation by AMPK and PPARα pathways in free fatty acid-treated HepG2 cells, thereby attenuating hepatic steatosis. Full article

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1_C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice. Full article

Peroxisome proliferator-activated receptor-alpha (PPAR-α) and its exogenous activators (fibrates) promote autophagy. However, whether the deleterious effects of PPAR-α deficiency on doxorubicin (DOX)-induced podocytopathy are associated with reduced autophagy remains to be clarified. We investigated the mechanisms of PPAR-α in DOX-induced podocytopathy and tubular injury in PPAR-α knockout (PAKO) mice and in a murine podocyte cell line. DOX-treated PAKO mice showed higher serum levels of triglycerides and non-esterified fatty acids and more severe podocytopathy than DOX-treated wild-type mice, as evidenced by higher urinary levels of proteins and podocalyxin at 3 days to 2 weeks and higher blood urea nitrogen and serum creatinine levels at 4 weeks. Additionally, there was an increased accumulation of p62, a negative autophagy marker, in the glomerular and tubular regions in DOX-treated PAKO mice at Day 9. Moreover, DOX-treated PAKO mice showed more severe glomerulosclerosis and tubular damage and lower podocalyxin expression in the kidneys than DOX-treated control mice at 4 weeks. Furthermore, DOX treatment increased p-p53, an apoptosis marker, and cleaved the caspase-3 levels and induced apoptosis, which was ameliorated by fenofibrate, a PPAR-α activator. Fenofibrate further enhanced AMPK activation and autophagy under fed and fasting conditions. Conclusively, PPAR-α deficiency enhances DOX-induced podocytopathy, glomerulosclerosis, and tubular injury, possibly by reducing autophagic activity in mouse kidneys. Full article

Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), result from an impairment of bile flow that leads to the hepatic retention of bile acids, causing liver injury. Until recently, the only approved treatments for PBC were ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). While these therapies slow the progression of PBC in the early stage of the disease, approximately 40% of patients respond incompletely to UDCA, and advanced cases do not respond. UDCA does not improve survival in patients with PSC, and patients often have dose-limiting pruritus reactions to OCA. Left untreated, these diseases can progress to fibrosis and cirrhosis, resulting in liver failure and the need for transplantation. These shortcomings emphasize the urgent need for alternative treatment strategies. Recently, nuclear hormone receptors have been explored as pharmacological targets for adjunct therapy because they regulate enzymes involved in bile acid metabolism and detoxification. In particular, the peroxisome proliferator-activated receptor (PPAR) has emerged as a therapeutic target for patients with PBC or PSC who experience an incomplete response to UDCA. PPARα is predominantly expressed in the liver, and it plays an essential role in the regulation of cytochrome P450 (CYP) and uridine 5’-diphospho-glucuronosyltransferase (UGT) enzymes, both of which are critical enzyme families involved in the regulation of bile acid metabolism and glucuronidation, respectively. Importantly, PPARα agonists, e.g., fenofibrate, have shown therapeutic benefits in reducing elevated markers of cholestasis in patients with PBC and PSC, and elafibranor, the first PPAR (dual α, β/δ) agonist, has been FDA-approved for the second-line treatment of PBC. Additionally, newer PPAR agonists that target various PPAR isoforms (β/δ, γ) are under development as an adjunct therapy for PBC or PSC, although their impact on glucuronidation pathways are less characterized. This review will focus on PPAR-mediated bile acid glucuronidation as a therapeutic pathway to improve outcomes for patients with PBC and PSC. Full article

Three peroxisome proliferator-activated receptor subtypes, PPARα, PPAR(ß/)δ, and PPARγ, exert ligand-dependent transcriptional control in concert with retinoid X receptors (RXRs) on various gene sets harboring PPAR response elements (PPREs) in their promoter regions. Ligand-bound PPAR/RXR complexes do not directly regulate transcription; instead, they recruit multiprotein coactivator complexes to specific genomic regulatory loci to cooperatively activate gene transcription. Several coactivators are expressed in a single cell; however, a ligand-bound PPAR can be associated with only one coactivator through a consensus LXXLL motif. Therefore, altered gene transcription induced by PPAR subtypes/agonists may be attributed to the recruitment of various coactivator species. Using a time-resolved fluorescence resonance energy transfer assay, we analyzed the recruitment of four coactivator peptides (PGC1α, CBP, SRC1, and TRAP220) to human PPARα/δ/γ-ligand-binding domains (LBDs) using eight PPAR dual/pan agonists (bezafibrate, fenofibric acid, pemafibrate, pioglitazone, elafibranor, lanifibranor, saroglitazar, and seladelpar) that are/were anticipated to treat nonalcoholic fatty liver disease. These agonists all recruited four coactivators to PPARα/γ-LBD with varying potencies and efficacy. Only five agonists (bezafibrate, pemafibrate, elafibranor, lanifibranor, and seladelpar) recruited all four coactivators to PPARδ-LBD, and their concentration-dependent responses differed from those of PPARα/γ-LBD. These results indicate that altered gene expression through consensus PPREs by different PPAR subtypes/agonists may be caused, in part, by different coactivators, which may be responsible for the unique pharmacological properties of these PPAR agonists. Full article

We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes’ expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly. Full article

Fenofibrate is a fibric acid derivative used as an antihyperlipidemic drug in humans. Its active metabolite, fenofibric acid, acts as an agonist to the peroxisome proliferator-activated receptor alpha (PPAR-α), a transcription factor involved in different metabolic pathways. Some studies have reported the potential protective role of this drug in cell lines and in vivo models against bacterial and viral infections. The aim of this study was to assess the in vitro effect of fenofibrate in the macrophage cell line J744A.1 against infections produced by Aeromonas, a pathogen for humans whose resistance to antibiotics has increased in recent decades. Macrophages were infected at MOI 10 with four strains of Aeromonas caviae and Aeromonas hydrophila isolated from human clinical samples and subsequently treated with fenofibrate. It was observed that fenofibrate-treated macrophages showed lower levels of cytotoxicity and intracellular bacteria compared to non-treated macrophages. In addition, the viability of treated macrophages was dependent on the dose of fenofibrate used. Furthermore, transcriptional analysis by RT-qPCR revealed significant differences in the expression of the PPAR-α gene and immune-related genes TNF-α, CCL3, and BAX in fenofibrate-treated macrophages compared to the macrophages without treatment. This study provides evidence that fenofibrate offered some protection in vitro in macrophages against Aeromonas infection. However, further studies are needed with other bacteria to determine its potential antibacterial effect and the route by which this protection is achieved. Full article

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy. Full article

Kidney dysfunction significantly increases the cardiovascular risk, even in cases of minor functional declines. Hypertriglyceridemia is the most common lipid abnormality reported in patients with kidney disorders. PPAR-α (peroxisome proliferator-activated receptor-α) agonists called fibrates are the main agents used to lower triglyceride levels. Kynurenic acid (KYNA) is a tryptophan (Trp) derivative directly formed from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KYNA is classified as a uremic toxin, the level of which is correlated with kidney function impairments and lipid abnormalities. The aim of this study was to analyze the effect of the most commonly used triglyceride-lowering drugs, fenofibrate and gemfibrozil, on KYNA production and KAT activity in rat kidneys in vitro. The influence of fenofibrate and gemfibrozil on KYNA formation and KAT activity was tested in rat kidney homogenates in vitro. Fenofibrate and gemfibrozil at 100 µM–1 mM significantly inhibited KYNA synthesis in rat kidney homogenates. Both fibrates directly affected the KAT I and KAT II isoenzyme activities in a dose-dependent manner at similar concentrations. The presented results reveal the novel mechanism of action of fibrates in the kidneys and suggest their potential role in kidney function protection beyond the well-known anti-hyperlipidemic effect. Full article