Search Results (264)

Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl₄-intoxicated Wistar rats. This study used a computational approach to assess the interaction of bioactive compounds with key proteins (CYP P450 3E1, TNF-α, and Cox-2). Methods:Wistar rats were treated with CCl₄ to induce liver injury and with different Nigella sativa fractions (250 mg/Kg) or Sylimarin (50 mg/Kg). Liver and kidney functions were assessed through biochemical markers, hepatic glycogen, malondialdehyde levels, molecular docking, and ADMET analysis to evaluate drug-likeliness. Results: The results revealed that intoxication with CCl₄ induced an elevation in different liver and kidney biochemical parameters such as (ALT, AST, creatinine, urea...) indicating kidney and hepatic toxicity. However, treatment with different Nigella sativa fractions showed a significant improvement in animal body weight and significant amelioration of biochemical markers indicating a protective potential of these fractions against CCl₄-induced intoxication. Furthermore, the molecular docking approach demonstrated high binding affinity with the target proteins. Conclusions: These current findings shed light on the therapeutic potential of Nigella sativa fractions as a promising protective agent of the liver and kidney against CCl₄ intoxication. Full article

Background: Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. Methods: We conducted a multicenter, retrospective observational study involving 156 patients with type 2 diabetes and chronic kidney disease (CKD) treated with subcutaneous semaglutide between 2019 and 2023. Inclusion required an eGFR > 15 mL/min/1.73 m² or albuminuria > 30 mg/g and at least two years of follow-up. The primary outcome was the change in eGFR slope after semaglutide initiation. Subgroup analyses were performed based on baseline eGFR, albuminuria, and SGLT2i co-treatment. Results: In the whole study population, the median eGFR slope significantly improved from −3.29 (IQR 7.54) to −0.79 (IQR 6.01) mL/min/1.73 m²/year post-treatment (p < 0.001). Multiple linear regression showed a hazard ratio for the effect of semaglutide on the eGFR slope of 4.06 (2.43–5.68), p < 0.001. In patients with baseline eGFR < 60 mL/min/1.73 m², the slope improved from −3.77 to −1.01 (p < 0.0001), while patients on concurrent SGLT2i therapy saw slope changes from −2.96 to −0.37 (p < 0.0001). Patients with albuminuria 30–1000 mg/g also improved from −2.96 to −0.04 (p < 0.0001); however, those > 1000 mg/g did not show a significant change (p = 0.184). Semaglutide also reduced BMI (p = 0.04), HbA1c (p = 0.002), triglycerides (p = 0.001), CRP (p = 0.003), and GGT values (p = 0.004). Conclusions: In real-world practice, semaglutide significantly attenuated renal function decline in high-risk diabetic patients, particularly those with advanced CKD or concurrent SGLT2i therapy. These findings support its nephroprotective role beyond glycemic control. Full article

Verbascoside is a polyphenolic compound that belongs to the phenylethanoid glucosides. It occurs in more than 220 plant species. The species with high content of this compound are used in folk medicine, and in modern phytotherapy, mostly based on its recognized anti-inflammatory and antimicrobial effects. Studies conducted so far confirmed these effects, and also pointed to others (i.e., anti-cancer, neuro-, cardio-, hepato-, and nephro-protective). This review presents data on the chemistry, occurrence, and biosynthesis of verbascoside. Additionally, it focuses on the cytotoxic, antimicrobial, anti-inflammatory, and immunomodulatory effects, as well as the main cellular and molecular mechanisms of its action. Full article

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)—small, non-coding RNA molecules involved in post-transcriptional gene regulation—have emerged as critical modulators of key pathogenic mechanisms in DKD, including fibrosis, inflammation, oxidative stress, and apoptosis. Numerous studies have identified specific miRNAs that either exacerbate or mitigate renal injury in DKD. Among them, miR-21, miR-192, miR-155, and miR-34a are associated with disease progression, while miR-126-3p, miR-29, miR-146a, and miR-215 demonstrate protective effects. These molecules are also detectable in plasma, urine, and renal tissue, making them attractive candidates for diagnostic and prognostic biomarkers. Advances in therapeutic technologies such as antagomiRs, mimics, locked nucleic acids, and nanoparticle-based delivery systems have opened new possibilities for targeting miRNAs in DKD. Additionally, conventional drugs, including SGLT2 inhibitors, metformin, and GLP-1 receptor agonists, as well as dietary compounds like polyphenols and sulforaphane, may exert nephroprotective effects by modulating miRNA expression. Recent evidence also highlights the role of gut microbiota in regulating miRNA activity, linking metabolic and immune pathways relevant to DKD progression. Further research is needed to define stage-specific miRNA signatures, improve delivery systems, and develop personalized therapeutic approaches. Modulation of miRNA expression represents a promising strategy to slow DKD progression and improve patient outcomes. Full article

Background: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD), responsible for approximately 60% of cases. Diabetic kidney disease (DKD) affects 20–50% of individuals with diabetes, with diabetes-related ESKD cases rising steadily worldwide from 22.1% in 2000 to 31.3% in 2015. Methods: This review examines the literature published up to 25 February 2025, using a systematic search in PubMed and Scopus. Keywords included uremic toxins and diabetic kidney disease and/or gut microbiota, or dysbiosis or gut–kidney axis. Studies were independently assessed by a minimum of three authors, with discrepancies resolved through consensus. Results: Gut microbiota dysbiosis is a key driver of DKD progression, making the gut–kidney axis a promising therapeutic target. A “nuts and fruits” dietary pattern reduces the DKD risk by 43.3%, while an animal protein intake lowers the diabetic peripheral neuropathy risk by 42.8%. High-fiber diets and supplements like resistant starch may reduce uremic toxins through microbiota modulation. Conclusions: Microbiota-targeted interventions, including probiotics, synbiotic, and dietary modifications, show potential in reducing uremic toxin production and inflammation, though DKD-specific evidence remains limited. Lactobacillus and Bifidobacterium strains may help lower urea and creatinine levels, but outcomes vary by disease stage. Further research is needed to confirm the efficacy of dietary and probiotic approaches in DKD management. Full article

The growing interest in functional foods has directed scientific attention toward alternative milk sources, particularly camel and donkey milk, which have been traditionally consumed for their purported health benefits across diverse cultures. These milk sources possess unique nutritional profiles and bioactive compositions that differ substantially from conventional bovine milk. This review examines the current scientific understanding of the anti-inflammatory and antioxidant bioactivities of camel and donkey milk, exploring their bioactive constituents and therapeutic potential. Camel and donkey milk demonstrate notable antioxidant and anti-inflammatory properties that may exceed those of conventional milk sources. Key bioactive compounds include lactoferrin, lysozyme, immunoglobulins, bioactive peptides, vitamins C and E, and polyunsaturated fatty acids. Mechanistic studies reveal that milk from donkeys and camels suppresses inflammatory pathways through NF-κB inhibition, cytokine modulation (reducing IL-6, IL-1β, and TNF-α while enhancing IL-10), and antioxidant pathway activation via Nrf2-ARE signaling. Donkey milk exhibits particularly high lysozyme content and demonstrates significant immunomodulatory effects, while camel milk shows remarkable therapeutic potential in diabetes management, nephroprotection, and hepatoprotection. Preclinical studies demonstrate efficacy in treating oxidative stress-related disorders, inflammatory conditions, metabolic dysfunction, and tissue injury models. Altogether, the published data show that camel and donkey milk represent promising functional foods with significant antioxidant and anti-inflammatory bioactivities mediated through multiple molecular pathways. Their unique bioactive profiles offer therapeutic potential for various health conditions, warranting further clinical investigation and development as nutraceutical interventions. Full article

Background/Objectives: Vancomycin-induced nephrotoxicity (VIN) remains a significant clinical challenge, with no effective nephroprotective agent currently established. This study aimed to evaluate the protective effects of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) against VIN in a Wistar albino rat model. Methods: Rats were randomly assigned to four groups: control, VA (vancomycin), DAPA (dapagliflozin), and VA+DAPA. Renal function was assessed by measuring serum urea and creatinine. Oxidative stress markers [malondialdehyde (MDA), total oxidant status (TOS), and myeloperoxidase (MPO)], antioxidant enzyme activities [total antioxidant status (TAS), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD)], apoptotic mediators (Bax, Bcl-2, and caspase-3), and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6)] were evaluated. Histopathological and immunohistochemical analyses of kidney tissues were also performed. Results: Administration of VA led to significant renal dysfunction, increased oxidative stress, heightened apoptotic activity, and notable histopathological damage. Co-administration of DAPA with VA significantly reduced serum urea and creatinine levels and decreased caspase-3 activity and was associated with a trend toward reduction in both MDA levels and TNF-α expression, as well as the amelioration of histopathological renal injury. However, reductions in IL-1β and IL-6 levels were not statistically significant. Overall, these findings indicate that DAPA exerts nephroprotective effects against VIN by modulating oxidative stress, inflammation, and apoptotic pathways. Conclusions: Dapagliflozin may serve as a potential protective agent against vancomycin-induced nephrotoxicity. Further long-term and large-scale clinical studies are warranted to validate these preclinical findings and explore their therapeutic implications. Full article

Acetaminophen, or paracetamol (PCM), is a common painkiller used to treat aches, pain, and fever. Nevertheless, PCM has been reported to be hepatotoxic and nephrotoxic in humans. Thus, there is a need to identify how this side effect can be treated. Previous studies have shown that Leea species possess antioxidative, anthelmintic, anti-cytotoxic, hepatoprotective, and nephroprotective properties. However, the role of Leea guineensis (LG) in modulating PCM-induced hepatotoxicity or nephrotoxicity remains unknown. Herein, we investigate the possibility of Leea guineensis leaf extract (LGE) to ameliorate PCM toxic effects, evaluate hepatic and renal function, oxidative stress markers, and safety, and perform molecular docking to predict affinities of Leea guineensis extract compounds for their targets compared to PCM. An in vivo rat model was used for Leea guineensis extract or silymarin (SLM, standard drug) at various concentrations, and it was co-administered with PCM. We observed that Leea guineensis extract is rich in phytochemical constituents, and its treatment in rats did not significantly affect body weight. Our data showed that PCM increased bilirubin, creatinine, uric acid, Alanine aminotransferase (ALT), and cholesterol levels but decreased Aspartate aminotransferase (AST) in plasma. Moreover, it increased lipid peroxidation (MDA) levels in the liver and kidneys, while the total protein was elevated in the latter. Interestingly, Leea guineensis extract and SLM abrogated the elevated parameters due to PCM toxicity. Importantly, histopathological examination showed that Leea guineensis extract demonstrated the potential to ameliorate hepatic and renal lesions caused by PCM intoxication, thus demonstrating its safety. Furthermore, comparative molecular binding affinities of the study ligands binding the target corroborate the experimental findings. Our study shows that L. guineensis leaf extract, through its rich phytochemicals, can protect the liver and kidneys against the toxic effects of paracetamol in a dose-dependent manner. Full article

Background: Diabetic kidney disease (DKD) affects 20–50% of individuals with diabetes. The aim of this review was to identify interventions that positively influence the gut microbiota in DKD. Methods: Identification of relevant studies was conducted via a systematic search of databases and registers using the PRISMA guidelines. This review examined the relevant literature published up to 5 January 2025, using a systematic search in PubMed and Scopus. The search was conducted with combinations of keywords including DKD and therapy, supplementation and gut microbiota, and supplementation or probiotics or fecal microbiota transplant. The initial search fielded 132 results from PubMed and 72 from Scopus, which was narrowed to 135 relevant studies. The exclusion criteria included non-English language studies, letters to the editor, and conference abstracts. Eligible studies were independently assessed by a minimum of three authors, with discrepancies resolved through consensus. Results: Gut microbiota-targeted interventions, including probiotics, synbiotics, and dietary modifications, show promise in modulating the gut microbiota, but evidence specific to DKD remains limited. Some natural food components such as polyphenols and anthocyanins modulate the composition of the gut microbiota translocation of uremic toxins, which slows down the progression of diabetic kidney disease. In animal models, fecal microbiota transplantation (FMT) has shown positive effects in regulating dysbiosis and beneficial effects in chronic kidney disease, but studies involving humans with DKD are insufficient. Conclusions: Lactobacillus and Bifidobacterium strains, administered at doses ranging from 0.6 to 90 billion CFU, may help lower urea and creatinine levels, but outcomes vary by disease stage, duration of therapy, and amount used. High-fiber diets (>10.1 g/1000 kcal/day) and supplements such as resistant starch and curcumin (400–1500 mg/day) may reduce uremic toxins through gut microbiota modulation and reduction in oxidative stress. The effect of sodium butyrate requires further human studies. Full article

The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This investigation sought to determine the nephroprotective potential of Lactobacillus rhamnosus GG (LGG) administration in diabetic nephropathy models. Six experimental cohorts were evaluated: control, probiotic-supplemented control, diabetic, diabetic receiving probiotic therapy, diabetic with antibiotics, and diabetic treated with both antibiotics and probiotics. Diabetic conditions were established via intraperitoneal administration of streptozotocin (50 mg/kg) following overnight fasting, according to validated protocols for experimental diabetes induction. Probiotic therapy (3 × 10⁹ CFU/kg, bi-daily) began one month before diabetes induction and continued throughout the study duration. Glycemic indices were monitored at bi-weekly intervals, inflammatory biomarkers, renal function indices, and urinary albumin excretion. The metabolic profile was evaluated through the determination of HOMA-IR and the computation of metabolic syndrome scores. Microbiome characterization employed 16S rRNA gene sequencing alongside metagenomic shotgun sequencing for comprehensive microbial community mapping. L. rhamnosus GG supplementation substantially augmented microbiome richness and evenness metrics. Principal component analysis revealed distinct clustering of microbial populations between treatment groups. The Prevotella/Bacteroides ratio, an emerging marker of metabolic dysfunction, normalized following probiotic intervention in diabetic subjects. Results: L. rhamnosus GG administration markedly attenuated diabetic progression, achieving glycated hemoglobin reduction of 32% compared to untreated controls. Pro-inflammatory cytokine levels (IL-6, TNF-α) decreased significantly, while anti-inflammatory mediators (IL-10, TGF-β) exhibited enhanced expression. The renal morphometric analysis demonstrated preservation of glomerular architecture and reduced interstitial fibrosis. Additionally, transmission electron microscopy confirmed the maintenance of podocyte foot process integrity in probiotic-treated groups. Conclusions: The administration of Lactobacillus rhamnosus GG demonstrated profound renoprotective efficacy through multifaceted mechanisms, including microbiome reconstitution, metabolic amelioration, and inflammation modulation. Therapeutic effects suggest the potential of a combined probiotic and pharmacological approach to attenuate diabetic-induced renal pathology with enhanced efficacy. Full article

Background: Systemic arterial hypertension is one of the leading global health concerns, significantly increasing the risk of cardiovascular and kidney diseases, including nephrolithiasis. The treatment, still far from ideal, is constantly undergoing new alternatives. In this context, medicinal plants rich in flavonoids, such as naringenin—a compound found in citrus fruits—have gained attention for their potential diuretic, nephroprotective, and blood pressure-lowering effects. Objectives: This study aimed to evaluate the effects of naringenin (100 mg/kg, orally) over nine days on blood pressure, renal function, and calcium oxalate crystal formation in normotensive Wistar (NTR) and spontaneously hypertensive male rats (SHR). Methods: Key assessments included blood pressure and heart rate measurements in vivo, urine volume and electrolyte excretion in vivo, in vitro calcium oxalate crystallization, and in silico molecular docking analyses to investigate molecular interactions. Results: Naringenin treatment significantly reduced blood pressure and increased diuresis in both NTR and SHR groups, while a notable natriuretic effect was observed specifically in NTR. In vitro, naringenin reduced the formation of calcium oxalate crystals in urines from NTR. Molecular docking studies suggested that these effects may be mediated by interactions with SGLT1 and SGLT2 transporters, potentially explaining the diuretic and natriuretic outcomes. Additionally, interactions with MMP-9 and β2-adrenergic receptors may contribute to the reduction in crystal formation. Conclusions: Collectively, these findings indicate that repeated administration of naringenin exerts beneficial effects on both cardiovascular and renal parameters, and point to promising molecular targets that may underlie its protective actions. Full article

Sodium–glucose cotransporter-2 inhibitors (SGLT2i), initially developed for the management of type 2 diabetes mellitus, have demonstrated significant nephroprotective and cardioprotective effects. These benefits have led to their inclusion in heart failure (HF) management guidelines, irrespective of glycemic status and left ventricular ejection fraction (LVEF). Various anticancer therapies, particularly anthracyclines, are associated with substantial cardiotoxicity risks, resulting in cancer therapy-related cardiovascular toxicity (CTR-CVT). Promising evidence from preclinical and observational studies indicates that SGLT2i may mitigate cardiotoxic effects of cancer therapy by alleviating LVEF decline, reducing HF incidence and hospitalizations, and lowering overall mortality. Moreover, improved survival has been reported in patients with various malignancies. The current review explores the potential applications of SGLT2i in the prevention of CTR-CVT, highlights their possible mechanisms of cardioprotection, discusses the published evidence, and emphasizes the need for the results from ongoing randomized controlled trials to establish SGLT2i efficacy and safety in cardio-oncology patients. Full article

Background/Objectives: The present study aimed to evaluate the nephroprotective role of Khellin (Khe) against cisplatin (CDDP)-mediated nephrotoxicity in rats. Methods: We assessed oxidative stress markers (MDA, CAT, SOD, GPx, and iNOs), inflammatory markers (TNFα, IL6, IL10, and MCP1), apoptotic markers (Bax and Bcl2), and the renal damage marker (Kim1). Network pharmacology and molecular docking studies were performed. In vitro, Khe effects were tested on normal kidney cells (Vero) and liver cancer cells (HepG2) treated with CDDP. Results: Network pharmacology and docking suggested Khe’s activity primarily affects oxidative stress and inflammatory pathways, notably through MAPK14 and PI3K downregulation. In vitro, Khe reduced CDDP’s cytotoxicity in Vero cells while maintaining anti-proliferative effects on HepG2 cells. In vivo, CDDP significantly increased serum creatinine, urea, Kim1, oxidative stress markers (MDA and iNOS), and inflammatory markers (TNFα, IL6, and MCP1) while decreasing antioxidant markers (SOD, GPx, CAT, and SOD3) and anti-inflammatory cytokine (IL10) levels. Khe treatment dose-dependently attenuated these changes, with the 100 mg/kg dose showing the most significant renoprotection. Histopathological analysis confirmed improved renal tissue integrity in Khe-treated groups. Conclusions: This study demonstrates that Khe exerts significant nephroprotective effects against CDDP-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis while improving renal function and structure. These findings suggest Khe as a promising therapeutic candidate for preventing CDDP-related kidney injury. Full article

High-sodium/low-potassium in the modern diet, potassium excretion, and sodium retention have all been implicated in hypertension. Objectives: This study investigated the differential effects of potassium (K⁺) supplementation on blood pressure, renal function, and oxidative stress in two experimental hypertensive rat models: L-NAME-induced (nitric oxide synthase inhibitor-induced hypertension presenting with reduced NO bioavailability, endothelial dysfunction, vasoconstriction) and DOCA-salt-induced hypertension (deoxycorticosterone acetate + salt mimics volume-dependent hypertension of hypermineralocorticoidism, low renin, high sodium retention and severe cardiac fibrosis and oxidative stress). Methods: Male Sprague Dawley rats were treated with L-NAME or DOCA-salt, with or without 0.75% KCl dietary supplementation for eight weeks. Blood pressure, vascular reactivity, serum electrolytes, renal function markers, and malondialdehyde (MDA) levels were evaluated. Results: Potassium supplementation significantly reduced (20%) mean arterial pressure and (80%) oxidative stress markers in the L-NAME model but not in the DOCA-salt model. In both hypertensive models, K⁺ reduced (15%) vascular contractile response to phenylephrine, though it did not improve acetylcholine-induced vasodilation. Notably, K⁺ supplementation improved glomerular filtration rate (eGFR), sodium–potassium ratio, and renal biomarkers (urea and creatinine) in the L-NAME model, suggesting nephroprotection. However, in the DOCA-salt group, these markers either remained unchanged or worsened. Conclusions: These findings indicate that the antihypertensive and renoprotective effects of potassium are model-specific and depend on the underlying pathophysiological mechanisms, such as nitric oxide bioavailability and mineralocorticoid sensitivity. Dietary potassium may be more effective in patients with endothelial dysfunction-dominant hypertensive subtypes compared with volume-dependent hypertension and may call for K⁺ supplementation studies to be stratified by hypertension subtype. Full article

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glycaemic control in type 2 diabetes, have demonstrated substantial renal and cardiovascular protective effects across various chronic kidney diseases (CKD), including glomerulonephritis. Beyond their established haemodynamic and metabolic benefits, recent evidence points to additional mechanisms of action potentially relevant to immune-mediated kidney diseases, such as the modulation of inflammation, immunometabolism, and oxidative stress. Randomised clinical trials (DAPA-CKD and EMPA-KIDNEY) and real-world observational studies consistently show that SGLT2 inhibitors reduce proteinuria and slow estimated glomerular filtration rate (eGFR) decline in patients with glomerulonephritis, including IgA nephropathy and focal segmental glomerulosclerosis. These benefits may extend to patients with stable immunosuppression. Further data are needed in this subgroup. Importantly, SGLT2 inhibitors display a favourable safety profile, even among those with immunosuppressed status. Again, further evidence is awaited in this respect. Despite these promising findings, unanswered questions remain regarding their efficacy in nephrotic syndrome, early-stage disease, and in comparison or combination with other supportive therapies. Overall, the evolving evidence supports the inclusion of SGLT2 inhibitors as a key component of supportive therapy in glomerulonephritis, with potential benefits extending beyond proteinuria reduction. Full article